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Background: Burning mouth syndrome (BMS) is a chronic pain condition affecting the oral cavity. This condition mostly affects peri‐ or postmenopausal women; for this reason, sexual hormonal changes have been implicated in BMS pathogenesis. Methods: A systematic review was performed in MEDLINE/PubMed, Scopus, Web of Science, Cochrane Library and EMBASE without restriction for language or year. Eligibility criteria were controlled studies addressing the PICO question: (P) patients with BMS; (I) detection of the sex hormones; (C) patients without BMS; (O) changes on sexual hormones as a risk factor for BMS severity. Risk of bias was performed with Newcastle‐Ottawa Quality Assessment Scale. Results: Four studies were included. Salivary levels were evaluated in three studies and serum blood was used in one. Three studies analysed oestradiol and/or dehydroepiandrosterone (DHEA), two assessed progesterone and one evaluated follicle‐stimulating hormone (FSH). Oestradiol results were contradictory, with two studies reporting lower levels in BMS patients compared to controls and one finding the opposite. DHEA was statistically lower in the BMS group in one study. Progesterone showed opposite results in two studies, although none with statistical significance. FSH was statistically higher in the BMS group compared to controls. Correlation of hormones with quality of life was performed in three studies and there was no significant correlation with self‐perceived symptoms severity. Conclusion: Sexual hormones can be altered in BMS, especially oestradiol. Despite these changes, we did not find correlation between hormone fluctuation and BMS symptoms intensity affecting quality of life. These findings suggested the need for further investigation on hormonal alterations, which may be a promising target on BMS management. [ABSTRACT FROM AUTHOR]

Problem: Preterm birth (PTB) is a significant cause of maternal and neonatal morbidity and mortality worldwide. However, the effectiveness of progesterone (P4) which is clinically used for PTB management remains controversial and necessitates research into new therapeutic options Method of Study: In the current study, we investigated the effectiveness of two chlorophyll derivatives, pheophorbide a (PBa) and pheophytin a (PTa), in counteracting PTB. Timed‐pregnant mice (gestation day 17 ± 0.5) received lipopolysaccharide (LPS) (25 µg/mouse) or phosphate‐buffered saline (PBS) intraperitoneally, with PBa, PTa, progesterone (P4), and co‐administration of P4 and ibuprofen (IBP), administered orally 2 h prior. Results: The LPS group experienced PTB and 100% fetal mortality, whereas the PBa and PTa groups showed a delayed onset of LPS‐induced PTB, with significantly decreased PTB rate and fetal mortality. In addition, PBa and PTa suppressed LPS‐induced pro‐inflammatory cytokines and NF‐κB transcription factor while increasing anti‐inflammatory cytokines in the placenta and uterus. Conclusions: Our findings indicate that the chlorophyll derivatives, PBa and PTa increase fetal survival in infection‐induced PTB and demonstrate greater efficacy than P4 in preventing PTB. [ABSTRACT FROM AUTHOR]

Aim: In frozen–thawed embryo transfer (FET), differences in endometrial preparation methods affect the incidence of perinatal complications. However, the underlying causes are unclear. We aimed to investigate whether serum E2, P4 levels are associated with perinatal complications. Methods: This is a retrospective cohort study, involving 306 successful FET pregnancies from 2017 to 2022. Participants were divided into Natural Cycle (NC) and Hormone Replacement Cycle (HRC) group. We compared serum hormone levels, maternal backgrounds, and perinatal outcomes and complications. Furthermore, within the HRC group, serum hormone levels were compared for perinatal complications previously reported to show differences in incidence rates depending on the method of endometrial preparation. Results: HRC exhibited significantly higher serum E2 levels during the implantation period, but lower P4 levels during ovulation, implantation, and pregnancy test period compared with NC. HRC also had significantly higher rates of postpartum hemorrhage (PPH) and placenta accreta spectrum (PAS). There was no association found between perinatal complications more likely to occur in HRC and serum E2, P4 levels. Conclusions: In HRC, there were more occurrences of PPH and PAS. Although serum E2, P4 levels during FET did not correlate with perinatal complications. [ABSTRACT FROM AUTHOR]

Hypersensitivity to exogenous or endogenous progesterone presents with a variety of clinical, usually cutaneous, manifestations. The condition can occur at any age during the reproductive years, causes debilitating symptoms and can impact the use of exogenous hormones. Management strategies include symptom control or hormonal manipulation via desensitisation. Strategic testing confirms the diagnosis, while targeted intervention can significantly and positively impact quality of life and further childbearing. [ABSTRACT FROM AUTHOR]

Introduction: Intrauterine insemination (IUI) is one of the most widespread fertility treatments. However, IUI protocols vary significantly amongst fertility clinics. Various add‐on interventions have been proposed to boost success rates. These are mostly chosen arbitrarily or empirically. The aim of this systematic review and meta‐analysis is to assess the effectiveness and safety of add‐on interventions to the standard IUI protocol and to provide evidence‐based recommendations on techniques used to optimize the clinical outcomes of IUI treatment. Material and Methods: Systematic review and meta‐analyses were performed in accordance with PRISMA guidelines. A computerized literature search was performed from database inception to May 2023. Randomized controlled trials (RCTs) were included reporting on couples/single women undergoing IUI with any protocol for any indication using partner's or donor sperm. A meta‐analysis based on random effects was performed for each outcome and add‐on. Three authors independently assessed the trials for quality and risk of bias and overall certainty of evidence. Uncertainties were resolved through consensus. Primary outcomes were ongoing pregnancy rate (OPR) or live birth rate (LBR) per cycle/per woman randomized. Registration number PROSPERO: CRD42022300857. Results: Sixty‐six RCTs were included in the analysis (16 305 participants across 20 countries). Vaginal progesterone as luteal phase support in stimulated cycles was found to significantly increase LBR/OPR (RR 1.37, 95% CI 1.09–1.72, I2 = 4.9%) (moderate/low certainty of the evidence). Endometrial scratch prior/during stimulated IUI cycles may increase LBR/OPR (RR 1.44, 95% CI 1.03–2.01, I2 = 1.8%), but evidence is very uncertain. Results from two studies suggest that follicular phase ovarian stimulation increases LBR/OPR (RR 1.39, 95% CI 1.00–1.94, I2 = 0%) (low certainty of evidence). No significant difference was seen for the primary outcome for the other studied interventions. Conclusions: The findings of this systematic review and meta‐analysis suggest that vaginal luteal phase progesterone support probably improves LBR/OPR in stimulated IUI treatments. In view of moderate/low certainty of the evidence more research is needed for solid conclusions. Further research is also recommended for the use of endometrial scratch and ovarian stimulation. Future studies should report on results according to subfertility background as it is possible that different add‐ons could benefit specific patient groups. [ABSTRACT FROM AUTHOR]

Aims Methods and results Conclusions The American Society of Clinical Oncology and College of American Pathologists HER2‐guidelines recommend repeat testing for most grade 1 mammary carcinomas that are HER2‐positive in the core biopsy. This study aimed to assess the value of repeat HER2‐testing and the histological features of HER2‐positive grade 1 carcinomas.A case‐series of HER2‐results of grade 1 carcinomas was conducted of patients with no pre‐operative systemic treatment over a 5‐year period. HER2‐positive carcinomas had histological review. Twelve HER2‐positive carcinomas were initially reported as grade 1. On review, two were reclassified as grade 2. The remaining 10 carcinomas represented 2% of the 508 grade 1 carcinomas. Eight HER2‐positive grade 1 carcinomas from other years were also studied. HER2‐positive carcinomas more often had marked nuclear pleomorphism (50 versus 6%) and were more often oestrogen receptor‐negative (17 versus 0.8%) and progesterone receptor‐negative (28 versus 8%) compared with HER2‐negative grade 1 carcinomas. Six carcinomas that were HER2 3+ in the core biopsy were also 3+ on repeat assessment. Five of seven carcinomas that were 2+ amplified in the core biopsy were also HER2‐positive in the excision.HER2‐positive grade 1 carcinomas are uncommon, and more often have marked nuclear pleomorphism and lack oestrogen receptor and progesterone receptor expression compared with HER2‐negative grade 1 carcinomas. A HER2‐poitive result in the core biopsy was confirmed in 11 of 13 tumours that had repeat testing. [ABSTRACT FROM AUTHOR]

Facioscapulohumeral dystrophy (FSHD) has a hypomethylation‐related epigenetic background and exhibits a different course in male and female patients. The differences between males and females have been linked to the levels of sex hormones. This study is the first to investigate the possible effect of these hormones on methylation status. We hypothesized that the levels of sex‐related hormones, estradiol, testosterone, progesterone, and prolactin might be associated with the methylation status of the proximal part of the D4Z4. We also investigated the effect of fT3, folic acid, and vitamin B12 levels. We collected blood from 28 FSHD patients and 28 controls. DNA was extracted from each individual for bisulfite methylation analysis and serum was separated for biochemical analysis of estradiol, testosterone, progesterone, prolactin, fT3, folic acid, and B12 analysis. Methylation analysis was specified to the DR1, 5P regions and the proximal region covering both DR1 and 5P. Methylation levels were compared between FSHD patients and controls. The correlation of methylation levels with estradiol, testosterone, progesterone, prolactin, fT3, folic acid, and B12 was investigated. We found that the 5P region and the proximal region were significantly hypomethylated in FSHD patients compared to the controls, but not the DR1 region. Male patients exhibited a significant reduction in DNA methylation compared to male controls. Older FSHD patients exhibited a notable decrease in fT3 levels and hypomethylation of the 5P region. Analyses of each CpG revealed seven hypomethylated positions that were significantly different from the control group. Two of the positions demonstrated a correlation with progesterone in the control group. With the exception of one position, the methylation levels were inversely correlated with vitamin B12 in FSHD patients. The results of our study indicate that the methylation of the proximal D4Z4 region, particularly at specific positions, may be associated with progesterone. In addition, vitamin B12 may be an indicator of hypomethylation. We suggest that examining position‐specific methylations may be a useful approach for the development of epigenetic treatment modalities. [ABSTRACT FROM AUTHOR]

Background: Repeat‐breeder cows repeatedly fail to conceive after at least three attempts and return to oestrus at apparently normal intervals. Repeat‐breeder cows cause economic losses in dairy farms in different ways. Objective: In the present study, we investigated the effect of sustained‐release progesterone injection in two different doses on the expression of interferon‐related genes in repeat‐breeder dairy cows. Methods: A total of 96 repeat‐breeder primiparous and multiparous cows were assigned among three groups: control group, inseminated and do not receive progesterone treatment; P400 and P600 groups, inseminated and received a single‐intramuscular injection of 400 and 600 mg slow‐release progesterone 5 days after insemination, respectively. Blood sampling was carried out on Day 20 after AI for progesterone measurement and evaluation of gene expression for ISG15, MX1 and MX2 genes. Results: One injection of sustained‐release progesterone increased the expression of ISG15, MX1 and MX2 genes with differences between two different progesterone concentrations. For all three genes, the level of gene expression was higher in progesterone‐supplemented group than in control group, when P400 and P600 groups considered together. The level of MX2 gene expression was significantly higher in pregnant cows than non‐pregnant cows. There was a significant positive correlation between expression level of all three genes and blood progesterone concentration. The expression level of ISG15 gene showed a significant positive correlation with MX1 and MX2 gene expression. Conclusion: The use of this sustained‐release progesterone is simple and can be used in repeat‐breeder cows to improve fertility. [ABSTRACT FROM AUTHOR]

Gender‐affirming hormone therapy (GAHT) is used by many transgender and gender‐diverse adults to align physical characteristics with their gender identity, reduce gender incongruence and improve psychological functioning. This narrative review provides an overview of the initiation and monitoring of GAHT in an Australian context. Trans individuals treated with testosterone typically receive standard testosterone doses and formulations recommended for cisgender men, whereas those receiving estradiol GAHT are typically treated with estradiol in combination with an anti‐androgen in those without orchidectomy. Proactive monitoring and mitigation of cardiovascular risk factors is pertinent in all transgender and gender‐diverse adults and bone health is an important consideration in those using estradiol GAHT. [ABSTRACT FROM AUTHOR]

Progesterone is an endogenous steroid hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. Progesterone crystallization techniques have previously reported. Among these techniques, solvent crystallization and different solvent:anti‐solvent systems are considered. Herein, the selective development of either hollow‐like or condensed progesterone microcrystals in elevated yield with controlled polymorphism, habit, and release is described for the first time. For the hollow microcrystals, isopropyl alcohol (IPA) and double‐deionized water (DDW) system is developed as solvent:anti‐solvent, while acetonitrile (AcN) and DDW system are developed for the condensed microcrystals. The microcrystals obtained from both developed crystallization systems are thoroughly investigated with varied microscopic techniques, including brightfield and scanning electron microscopy (SEM), thermal analysis by differential scanning calorimetry (DSC), and crystallography by powder X‐ray diffraction (PXRD) and single XRD, and have been compared. Results show that the crystals of the IPA:DDW crystallization system are hollow and exhibit several habits, whereas the microcrystals of the AcN:DDW crystallization system are more condensed. However, both systems are found to have a wide crystal size distribution of one stable polymorph and are thus highly useful for tunable release. More importantly, these microcrystals exhibit elongated and slow release for 14 days under an expedited release conditions model, indicating suitability for long‐term and potential localized release applications. [ABSTRACT FROM AUTHOR]

We examined performance across one menstrual cycle (MC) and 3 weeks of hormonal contraceptives (HC) use to identify whether known fluctuations in estrogen and progesterone/progestin are associated with functional performance changes. National Rugby League Indigenous Women's Academy athletes [n = 11 naturally menstruating (NM), n = 13 using HC] completed performance tests [countermovement jump (CMJ), squat jump (SJ), isometric mid‐thigh pull, 20 m sprint, power pass and Stroop test] during three phases of a MC or three weeks of HC usage, confirmed through ovulation tests alongside serum estrogen and progesterone concentrations. MC phase or HC use did not influence jump height, peak force, sprint time, distance thrown or Stroop effect. However, there were small variations in kinetic and kinematic CMJ/SJ outputs. NM athletes produced greater mean concentric power in MC phase four than one [+0.41 W·kg−1 (+16.8%), p = 0.021] during the CMJ, alongside greater impulse at 50 ms at phase one than four [+1.7 N·s (+4.7%), p = 0.031] during the SJ, without differences between tests for HC users. Among NM athletes, estradiol negatively correlated with mean velocity and power (r = −0.44 to −0.50, p < 0.047), progesterone positively correlated with contraction time (r = 0.45, p = 0.045), and both negatively correlated with the rate of force development and impulse (r = −0.45 to −0.64, p < 0.043) during the SJ. During the CMJ, estradiol positively correlated to 200 ms impulse (r = 0.45, p = 0.049) and progesterone to mean power (r = 0.51, p = 0.021). Evidence of changes in testing performance across a MC, or during active HC use, is insufficient to justify "phase‐based testing"; however, kinetic or kinematic outputs may be altered in NM athletes. Highlights: Evidence of changes in testing performance across a menstrual cycle, or during active hormonal contraceptives use, is insufficient to justify "phase‐based testing" at a group or team‐based level among female rugby league athletes.Kinetic or kinematic outputs in jumping movements may be altered in naturally menstruating athletes; however it could not be determined if the observed alterations exceeded between‐day variability. [ABSTRACT FROM AUTHOR]

A number of methods are currently used to predict the optimal date of insemination of the breeding bitch, particularly with the use of frozen–thawed canine semen which has a far shorter lifespan than fresh semen. Aside from confirming cytological oestrus, vaginal cytology is of no assistance in predicting the most fertile day(s) in a bitch; however, a neglected avenue of research suggests that vaginal cytology may be of great importance in confirming the days of optimal fertility retrospectively. Similarly, vaginoscopy provides clues as to the stage of a bitch's cycle but is inadequate as a sole determinant of her most fertile days. Nevertheless, vaginoscopy is useful to identify very late oestrus and the onset of dioestrus, as well as Stage I of labour (cervical dilatation). Due to variations in the rate at which circulating progesterone concentrations rise in individual bitches, the reliability of circulating progesterone concentrations for determining the optimal day(s) of insemination with frozen–thawed semen decreases as values rise. Moreover, progesterone assay results can vary widely due to extrinsic factors such as the time of blood sampling, sample storage conditions and the assay employed. Finally, this review investigates evidence surrounding various insemination routes and suggests that well‐performed vaginal insemination, even with frozen–thawed semen, may be an acceptable approach for cases where transcervical insemination is impractical. [ABSTRACT FROM AUTHOR]

This study compared reproductive outcomes among two protocols for synchronization of ovulation that provide for a lengthened proestrus with the conventional oestradiol‐based protocol currently used for timed‐AI (TAI). Holstein heifers (13–15 months) at one location were assigned randomly to one of three TAI protocols. Heifers (n = 150) in the 7‐day oestradiol benzoate (EB) group received a progesterone device (Cue‐Mate) and 2 mg EB on Day 0; 500 μg of cloprostenol (PGF) and Cue‐Mate removal on Day 7; 1 mg of EB on Day 8 and TAI on Day 9 (54 h after Cue‐Mate removal). Heifers (n = 150) in the 5‐day CO‐Synch (CO) group received a Cue‐Mate and 100 μg of gonadotropin‐releasing hormone (GnRH) on Day 2; Cue‐Mate removal and PGF (twice, 12 h apart) on Day 7; and GnRH along with TAI on Day 10 (72 h after Cue‐Mate removal). Heifers (n = 150) in the J‐Synch (JS) group received a Cue‐Mate and 2 mg of EB on Day 1; PGF and Cue‐Mate removal on Day 7; GnRH and TAI on Day 10 (72 h after Cue‐Mate removal). Heifers were inseminated by one technician with frozen–thawed conventional semen from one of four commercially available sires. Plasma progesterone (P4) concentrations (ng/mL) were determined at Cue‐Mate removal and TAI. Ovarian ultrasonography was done in a subset of 217 heifers at the initiation of protocols, at Cue‐Mate removal; TAI; and 7 days after TAI. Approximately, 28 and 50 days after TAI pregnancy status was determined by ultrasonography. Mean (±SEM) plasma P4 concentration at Cue‐Mate removal was greater (p <.01) in CO (6.02 ± 0.2) and JS (6.51 ± 0.2) compared to EB heifers (4.53 ± 0.2). Mean (±SEM) plasma P4 concentration at TAI was lowest in the JS (0.28 ± 0.05), intermediate in CO (0.46 ± 0.02), and greatest in EB heifers (0.66 ± 0.05, p <.01). The diameter of the ovulatory follicle (mean ± SEM) was the smallest in the JS group compared to that in the CO and EB groups (15.8 ± 0.5; 13.9 ± 0.5; and 12.7 ± 0.5 mm for EB, CO and JS, respectively). More (p <.01) heifers in the JS group had their oestrous cycle synchronized (50.0, 78.8 and 82.4% for EB, CO and JS groups), and were pregnant at 28 (40.3, 51.3 and 63.3% for EB, CO and JS groups) and 50 days after TAI (32.6, 46.0 and 60.0% for EB, CO and JS groups). In summary, heifers subjected to the J‐Synch TAI protocol had lower P4 at TAI, and better overall response to hormonal treatments, which resulted in increased P/AI at 28 and 50 days after TAI compared to those heifers subjected to either a 7‐day EB protocol or a 5‐day CO‐synch protocol. [ABSTRACT FROM AUTHOR]

Background and Aims: One of the causes of preterm labor and recurrent abortion is progesterone deficiency in the luteal phase. The aim of the study was a comparison of the effect of oral dydrogesterone and vaginal progesterone for luteal‐phase support (LPS) in assisted reproductive technology cycles (ART). Methods: This randomized clinical control trial study was conducted on 207 infertile women. Samples were randomly divided into two groups. The first group received a natural micronized vaginal progesterone (MVP) of 400 mg once daily and the second group received dydrogesterone (Duphestone) 20 mg twice daily. Then chemical pregnancy, abortion, and live births were compared in two groups. Results: The results of the study showed that the vaginal form of the drug could increase the chance of pregnancy (positive β‐human chorionic gonadotropin) versus the oral form. According to the results of multiple logistic regression analysis after adjusting for other variables, the live birth rate in the vaginal group was more than five times that of the oral group (odds ratio = 5.07; 95% confidence interval = 1.24–20.65; p = 0.023). Conclusion: The vaginal form of the progesterone could increase the chance of pregnancy and the outcome of fertility (live birth). Thus, vaginal progesterone is effective for LPS in women undergoing fresh embryo transfer. [ABSTRACT FROM AUTHOR]

This study evaluated the relationship between CL features assessed by ultrasound (luteal tissue area and blood flow, BF) or rectal palpation (size), uterine tone (UT), plasma progesterone (P4) concentration on Day 7 (D7) and subsequent pregnancy outcomes in bovine embryo recipients. A total of 163 cows and heifers were included in this study. The expected day of ovulation after the synchronization protocol was designated as D0. On D7, ovaries and uterus were examined by ultrasonography and rectal palpation, and subjective scores (1–3 scale) were assigned for CL size, area and BF, and for UT. Blood samples were collected for further P4 analysis. Each embryo recipient then received a grade I frozen–thawed in vivo‐produced blastocyst, which was transferred to the uterine horn ipsilateral to the CL. Pregnancy diagnosis was performed on D35, and the results were retrospectively compared with the assigned scores for CL and UT. We observed a significant (p <.02) interaction between CL size and UT, with a progressive increase in the likelihood of pregnancy for recipients bearing a large CL among those with turgid UT. Ultrasound scoring of the CL using B‐mode and Doppler‐mode did not significantly predict pregnancy rates on D35 (p <.6 and p <.5, respectively). However, logistic regression analysis revealed a trend towards a quadratic effect (p <.08 and p <.06) indicating that the probability of pregnancy varied according to the area of luteal tissue and P4 concentrations, respectively. No significant (p >.05) association was found between the probability of pregnancy and the BF area of the CL. In summary, UT before embryo transfer may reflect successful recipient synchronization. Elevated P4 levels, assessed by CL size, may offset uterine contractility, mitigating adverse effects. Additionally, the CL area may be more important than its vascularization area when evaluating recipients D7 after ovulation. [ABSTRACT FROM AUTHOR]

Context: Meditation and related relaxation techniques are good means of alleviating stress and maintaining good health. Osho dynamic meditation decreases several psychopathological variables such as anxious‐depressive syndrome, aggressive behaviors, and depression which is practiced in Nepal and all over the world. Various studies have shown alteration in different hormone levels due to meditation by strengthening adaptive mechanisms. Aim: The aim of this study was to evaluate the effect of Osho meditation on serum hormonal levels in pre‐ and postmeditation participants. Methods: A pre–post study was conducted among 70 healthy volunteers (42 male and 28 female) where various types of Osho dynamic meditation techniques were incorporated together to understand their combined effects on serum hormone levels in participants attending the 7 days meditation camp. Serum hormones such as cortisol, estrogen, progesterone, free triiodothyronine (fT3), free thyroxine (fT4), thyroid‐stimulating hormone (TSH), testosterone, and growth hormone were measured by chemiluminescence immunoassay. Results: Out of 70 participants, 68 participants (97%) had subjective opinion of Osho dynamic meditation being effective in alleviating stress, depression, and anger. Also, there was a significant decline in body weight and body mass index in both male and female populations after a strict vegetarian diet and meditation. Likewise, a significant rise in the level of estrogen (p < 0.001), progesterone (p < 0.001), growth hormone (p < 0.001), testosterone (p = 0.002), and fT3 (p = 0.049) in postmeditation male participants indicates the importance of Osho dynamic meditation on elevating sex hormones such as estrogen, progesterone, testosterone as well as fT3, and growth hormones among Osho meditation practicing participants. Conclusion: Our findings suggest significant changes in the hormonal levels and improvement in stress and depression in participants undergoing Osho meditation. [ABSTRACT FROM AUTHOR]

Background: PGF2α is commonly given at the end of embryo flushing (EF) to shorten the interval to the next oestrus and ovulation. Objectives: To determine the effect of repeated EF on plasma progesterone concentration, percentage of mares with endometritis, unwanted pregnancy and subsequent fertility in mares flushed without the use of PGF2α. Study design: Controlled experiments. Methods: Nine mares were inseminated in seven consecutive cycles (n = 63), to either perform an EF (n = 54) 7–9 days after ovulation or left pregnant (n = 9). PGF2α was not used to induce oestrus. Ultrasound examination and blood sampling were performed just before the EF and 72 h later to determine changes in progesterone concentration and signs of endometritis. Results: The overall percentage of positive EF/pregnancy was 55.5% (30/54) and 66.7% (6/9), respectively. The likelihood of pregnancy/positive EF in the first three cycles was 55.5% (15/29). This was not different (p > 0.1) from the fertility of the last four cycles (69.4%, 25/36). In five EF cycles (9.3%), mares had signs of endometritis and early luteolysis (progesterone <2 ng/mL) 72 h after EF. The reduction in progesterone concentration by 72 h after EF was greater (p < 0.05) for Day 9 (−2.3 ± 0.7 ng/mL) than Day 7 (−1.0 ± 0.8 ng/mL) or Day 8 (−1.3 ± 1.1 ng/mL) cycles. The progesterone concentration in non‐flushed mares did not vary significantly during the sampled period (Day 7–12). There were 5 cycles in which the donor mare remained pregnant after the EF, although four were from a single mare. Main limitations: The mare population was limited to barren and maiden mares. The cycle order and operator allocation to each EF were not randomised. Conclusions: EF induces a subtle, but significant reduction in progesterone concentrations compared with non‐EF cycles. However, the percentage of mares with EF‐induced full luteolysis is low (9.3%). The fertility of mares after repeated EF without administration of PGF2α was unaffected; however, there is a considerable risk of unwanted pregnancy (5/27 = 18.5%) in donors from which an embryo was not recovered. [ABSTRACT FROM AUTHOR]

Steroidogenic tissues contain cytosolic lipid droplets that are important for steroidogenesis. Perilipin 2 (PLIN2), a structural coat protein located on the surface of lipid droplets in mammalian cells, plays a crucial role in regulating lipid droplet formation and contributing to various cellular processes such as lipid storage and energy homeostasis. Herein, we examine the role that PLIN2 plays in regulating progesterone synthesis in the bovine corpus luteum. Utilizing gene array databases and Western blotting, we have delineated the expression pattern of PLIN2 throughout the follicular to luteal transition. Our findings reveal the presence of PLIN2 in both ovarian follicular and steroidogenic luteal cells, demonstrating an increase in its levels as follicular cells transition into the luteal phase. Moreover, the depletion of PLIN2 via siRNA enhanced progesterone production in small luteal cells, whereas adenovirus‐mediated overexpression of both PLIN2 and Perilipin 3 (PLIN3) induced an increase in cytosolic lipid droplet accumulation and decreased hormone‐induced progesterone synthesis in these cells. Lastly, in vivo administration of the luteolytic hormone prostaglandin F2α resulted in an upregulation of PLIN2 mRNA and protein expression, accompanied by a decline in serum progesterone. Our findings highlight the pivotal role of PLIN2 in regulating progesterone synthesis in the bovine corpus luteum, as supported by its dynamic expression pattern during the follicular to luteal transition and its responsiveness to luteotropic and luteolytic hormones. We suggest PLIN2 as a potential therapeutic target for modulating luteal function. [ABSTRACT FROM AUTHOR]

Objective: To compare the hypertensive disorders of pregnancy (HDP) risk between vaginal and intramuscular (IM) progesterone in programmed frozen–thawed embryo transfer (FET) cycles. Methods: This was a retrospective cohort study at a tertiary hospital, and only women who achieved ongoing pregnancy after programmed FET between January 2018 and June 2022 were included. Women with chronic hypertension before pregnancy or with history of gestational hypertension or pre‐eclampsia in previous pregnancies were excluded. All women were divided into IM progesterone or vaginal progesterone groups according to the route of progesterone supplementation. Follow‐up information on obstetric complications and neonatal outcomes were obtained by telephonic interviews. The primary outcome was HDP. Association between routes of progesterone supplementation and HDP was assessed by subgroup analysis and multivariable logistic regression. Results: A total of 5891 programmed FET cycles (3196 IM progesterone cycles and 2695 vaginal progesterone cycles) were included in the analysis. The prevalence of HDP in the IM progesterone group was significantly lower than that of the vaginal progesterone group (6.54% vs 9.17%, P < 0.001). Therein, the prevalence of gestational hypertension (3.57% vs 4.94%, P = 0.009) and pre‐eclampsia (2.97% vs 4.23%, P = 0.009) in the IM progesterone group were all significantly lower as compared to the vaginal progesterone group. According to subgroup analysis, IM progesterone was associated with lower HDP risk in all subgroups. The logistic regression analysis showed that the IM progesterone cycles were associated with lower risk of HDP compared to vaginal progesterone cycles (adjusted odds ratio 0.66, 95% CI: 0.54–0.80, P < 0.001). Conclusion: Among women undergoing programmed FET cycles, progesterone supplementation with IM progesterone was associated with reduced HDP risk compared to vaginal progesterone. Synopsis: Luteal support of intramuscular progesterone was associated with lower gestational hypertension as compared to vaginal progesterone in programmed frozen–thawed embryo transfer cycles. [ABSTRACT FROM AUTHOR]

Understanding the normal physiology of the canine mammary gland (CMG) is crucial, as it provides a foundational reference for understanding canine mammary neoplasms. The relation between the Proliferation Index (PI) indicated by Ki‐67 expression, along with the Apoptotic Index (AI) determined through Caspase‐3 expression during the oestrous cycle, is inadequately documented in existing literature. This study seeks to offer insights into the interplay between PI and AI in the CMG across oestrous cycle phases. An extensive investigation was conducted on a diverse case series of bitches (n = 18). Oestrous cycle stages were determined through vaginal cytology, histological examination of the reproductive tract and serum progesterone and oestradiol concentrations. The entire mammary chain was histologically examined, and proliferation and apoptosis were assessed via double immunohistochemistry employing anti‐Ki‐67 and Caspase‐3 antibodies. PI and AI were evaluated through a systematic random sampling approach, counting a minimum of 200 cells for each cell type. There was a significantly higher PI during early dioestrus in all mammary gland components, with a greater proportion of positive cells observed in epithelial cells compared to stromal cells. The highest PI was detected in epithelial cells within the end buds. Significant differences were found in Ki‐67 labelling across the cranial mammary glands. A positive and strong correlation was noted between progesterone concentration and PI in epithelial cells. The AI remained consistently low throughout the oestrous cycle, with few differences observed across histological components. Caspase‐3 labelling displayed the highest positivity in caudal mammary pairs. A negative and moderate correlation was identified between progesterone concentration and AI in interlobular mesenchymal cells. This study highlights the influence of endocrine regulation on cell proliferation indices in mammary tissue, emphasizing the need to consider these hormonal variations in toxicopathological studies involving canine mammary gland. [ABSTRACT FROM AUTHOR]

The cervix is an important organ that has to dilate sufficiently at delivery to allow the foetus to transition to extrauterine life. Insufficient dilatation of the cervix (IDC) is a frequent cause of dystocia in cattle. The mechanisms underlying cervical opening and the pathogenesis of IDC are still widely unclear. Systematic studies on the relationship between IDC and steroid hormones have been limited and have yielded inconsistent findings. This study aimed to measure oestrogen and progesterone (P4) concentrations in intrapartum cows presented with dystocia due to IDC and in a comparison (C) group of cows with eutocic delivery. Before any obstetrical procedures, and right after the initial evaluation, blood samples were taken from IDC and C animals. Concentrations of P4, oestradiol‐17β (E2), free total oestrogens (FTE) and conjugated total oestrogens (CTE) were measured by established radioimmunoassays. Concentrations of P4 (p =.538), FTE (p =.065) and CTE (p =.605) were not statistically different between C and IDC groups. However, E2 levels in group C were significantly lower when compared to those in the IDC group (p =.013), which is inconsistent with the function of oestrogens in cervical dilatation. The correlation analysis demonstrated significant positive correlations between the pairs P4 versus FTE, P4 versus E2 and FTE versus E2 in group C and between the pair FTE versus E2 in group IDC. In conclusion, the results suggest that local activities of steroids relevant to the aetiology of IDC are not reflected by concentrations in the systemic circulation or that other factors are clearly more important. [ABSTRACT FROM AUTHOR]

Progesterone has been shown to stimulate glycogen catabolism in uterine epithelial cells. Acid α‐glucosidase (GAA) is an enzyme that breaks down glycogen within lysosomes. We hypothesized that progesterone may stimulate glycogenolysis in the uterine epithelium via GAA. We found that GAA was more highly expressed in the stroma on Day 1 than on Day 11. However, GAA did not appear to differ in the epithelium on Days 1 and 11. Progesterone (0‐10 μM) had no effect on the levels of the full‐length inactive protein (110 kDa) or the cleaved (active) peptides present inside the lysosome (70 and 76 kDa) in immortalized bovine uterine epithelial (BUTE) cells. Furthermore, the activity of GAA did not differ between the BUTE cells treated with 10 μM progesterone or control. Overall, we confirmed that GAA is present in the cow endometrium and BUTE cells. However, progesterone did not affect protein levels or enzyme activity. [ABSTRACT FROM AUTHOR]

Sub‐estrus buffaloes do not exhibit estrus signs despite being cyclic contributing to extended service periods and inter‐calving intervals causing significant economic loss. The present study described the effect of synthetic prostaglandin (PGF2α) on estrus behaviour, follicular and luteal morphometry, and serum estradiol (E2) and progesterone (P4) profile in sub‐estrus buffaloes during the non‐breeding season. The incidence of sub‐estrus was 38.4% during the non‐breeding season. The sub‐estrus buffaloes (n = 33) were divided into two groups, viz., Control (n = 16) and PGF2α treatment (Inj. Cloprostenol 500 μg, i.m., n = 17). Estrus induction response was significantly greater in the treatment (100 vs. 18.75%, p <.001), and a relatively greater proportion of animals conceived in the treatment group (29.41 vs. 6.25%, p =.08). The time elapsed to induction of estrus and insemination following treatment was significantly lower in the treatment group than control. A significant increment in the follicle diameter (9.72 ± 0.45 vs. 13.00 ± 0.45 mm, P <.0001) and serum estradiol (E2) concentration (66.01 ± 11.92 vs. 104.9 ± 13.21 pg/mL, p =.003) observed at the post‐treatment period in the PGF2α treatment group. At the same time, CL diameter was reduced significantly at a higher regression rate in the PGF2α treated buffaloes than those of control. Of the responded buffaloes, only 30% showed high‐intensity estrus attributed to the expulsion of cervico‐vaginal mucus (CVM), uterine tonicity, micturition, and mounting response by a teaser bull. From this study, it can be concluded that the administration of PGF2α could induce estrus in the sub‐estrus buffaloes during the non‐breeding season. Behavioural changes, along with sonographic observation of POF, regressing CL, and serum E2 and P4 concentration would be useful to determine the right time of insemination in sub‐estrus buffaloes during non‐breeding season. [ABSTRACT FROM AUTHOR]

This study evaluated whether the treatment of pseudopregnancy in bitches with vitamin B6 modulates uterine expression of receptors for progesterone (PR), oestrogen (ERα), androgen (AR), thyroid hormone (TRα) and the kisspeptin/Kiss1r system. Eighteen pseudopregnant bitches were treated for 20 days in groups receiving placebo (n = 6); cabergoline (5 μg/kg/day; n = 6); or vitamin B6 (50 mg/kg/day; n = 6). Blood was collected on the 1st day of drug administration and 120 h later to measure serum prolactin (PRL). After treatment, they were ovariohysterectomized and uterine fragments were collected for histomorphometry and immunohistochemical evaluation of PR, ERα, AR, TRα, Kiss1 and Kiss1r. After 120 h of cabergoline or vitamin B6 treatment, PRL levels were reduced in the bitches, confirming the antiprolactinemic effect of these drugs. Furthermore, regardless of treatment, the animals exhibited uterine histomorphometry consistent with dioestrus. The PR showed strong immunostaining in all regions and an increase in scores was observed for this receptor in animals treated with vitamin B6 in deep glands. In contrast, ERα and Kiss1R receptors showed weak to no immunostaining in all uterine regions and no changes between groups. Regarding AR, most animals treated with vitamin B6 showed increased trends in the deep gland and myometrium marking scores. In contrast, in both vitamin B6 and cabergoline treatments, a reduction in TRα marking scores was observed compared to the control group. In addition, on the endometrial surface, a reduction was observed in the marked area of Kiss1 after administration of cabergoline when compared to the pseudopregnant control group. These findings shed valuable insight into the use of vitamin B6 as a drug with actions similar to cabergoline in reducing PRL and uterine modulation in bitches. [ABSTRACT FROM AUTHOR]

Background: Treatment with vaginal progesterone reduces the risk of miscarriage and preterm birth in selected high‐risk women. The hypothesis that vaginal progesterone can reduce the risk of hypertensive disorders of pregnancy (HDP) is unexplored. Objectives: To summarise the evidence on the effectiveness of vaginal progesterone to reduce the risk of HDP. Search strategy: We searched Embase (OVID), MEDLINE (OVID), PubMed, CENTRAL and clinicaltrials.gov from inception until 20 June 2023. Selection criteria: We included placebo‐controlled randomised trials (RCTs) of vaginal progesterone for the prevention or treatment of any pregnancy complications. Data collection and analysis: We extracted absolute event numbers for HDP and pre‐eclampsia in women receiving vaginal progesterone or placebo, and meta‐analysed the data with a random effects model. We appraised the certainty of the evidence using GRADE methodology. Main results: The quantitative synthesis included 11 RCTs, of which three initiated vaginal progesterone in the first trimester, and eight in the second or third trimesters. Vaginal progesterone started in the first trimester of pregnancy lowered the risk of any HDP (risk ratio [RR] 0.71, 95% confidence interval [CI] 0.53–0.93, 2 RCTs, n = 4431 women, I2 = 0%; moderate‐certainty evidence) and pre‐eclampsia (RR 0.61, 95% CI 0.41–0.92, 3 RCTs, n = 5267 women, I2 = 0%; moderate‐certainty evidence) when compared with placebo. Vaginal progesterone started in the second or third trimesters was not associated with a reduction in HDP (RR 1.19, 95% CI 0.67–2.12, 3 RCTs, n = 1602 women, I2 = 9%; low‐certainty evidence) or pre‐eclampsia (RR 0.97, 95% CI 0.71–1.31, 5 RCTs, n = 4274 women, I2 = 0%; low‐certainty evidence). Conclusions: Our systematic review found first‐trimester initiated vaginal micronised progesterone may reduce the risk of HDP and pre‐eclampsia. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to investigate the current status of progestogen treatment for pregnant women at a high risk for preterm birth (PTB) in childbirth healthcare facilities in Japan. Methods: A web‐based nationwide questionnaire survey regarding progestogen use for prevention of PTB was conducted among childbirth healthcare facilities from 2019 to 2021. Results: Valid responses were obtained from 528 facilities (25.2% of those surveyed), including 155 tertiary perinatal facilities (making up 92.3% of all tertiary perinatal care facilities). In the survey period, progestogen treatment was implemented in 207 facilities (39.2%) for PTB prevention. Regarding types of progestogens, 17α‐hydroxyprogesterone caproate was used in 170 facilities (82.1%), with a low dose (125 mg/week) administered in 62.9% of the facilities to comply with the regulations of the national health insurance system, although 250 mg/week is considered the best dose. Vaginal progesterone was used in 36 facilities (17.4%), although the cost of vaginal progesterone was not covered by health insurance. Of the facilities not administering progestogen treatment, approximately 40% expressed that vaginal progesterone would be their first choice for PTB prevention in daily practice if it would be covered by health insurance in the future. Conclusions: Due to the current regulations of the Japanese health insurance system, 17α‐hydroxyprogesterone caproate, rather than vaginal progesterone, was mainly used for PTB prevention. Despite global evidence supporting vaginal progesterone as the approach with the highest efficacy, only a limited number of facilities have utilized it due to the current drug use regulations in Japan. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the association between changes in cervical length (CL) after vaginal progesterone treatment and preterm delivery (PTD). Methods: This was a retrospective cohort study that included 197 singleton pregnancies without (n = 178) and with (n = 19) a history of PTD which were found to have a short cervix (≤ 25 mm) between 18 + 0 and 23 + 6 weeks' gestation with a follow‐up transvaginal CL measurement taken at least 1 week after vaginal progesterone treatment started. Receiver‐operating‐characteristics (ROC)‐curve analysis was performed and three CL shortening patterns were evaluated: (1) ≥ 10% reduction; (2) ≥ 20% reduction; and (3) ≥ 5 mm reduction relative to the first CL measurement. The predictive performance of each CL reduction cut‐off and its association with PTD ≤ 34 weeks and PTD < 37 weeks were evaluated. Results: Overall, the rate of PTD ≤ 34 weeks was 16.8% (33/197) and that of PTD < 37 weeks was 36.5% (72/197). The area under the ROC curve of cervical shortening expressed in % for predicting PTD ≤ 34 weeks and PTD < 37 weeks was 0.703 and 0.608, respectively. Cervical shortening was observed in 60/197 (30.5%) patients, with 49/60 (81.7%) women showing ≥ 10% reduction, 32/60 (53.3%) ≥ 20% reduction and 27/60 (45.0%) ≥ 5 mm reduction in CL. Sensitivity and specificity for PTD ≤ 34 weeks were, respectively, 48.5% and 79.9% for ≥ 10% reduction; 36.4% and 87.8% for ≥ 20% reduction; and 27.3% and 89.0% for ≥ 5 mm reduction in CL. For PTD < 37 weeks, sensitivity and specificity were, respectively, 36.1% and 81.6% for ≥ 10% reduction; 27.8% and 90.4% for ≥ 20% reduction; and 20.8% and 90.4% for ≥ 5 mm reduction in CL. The highest positive likelihood ratios for PTD ≤ 34 and < 37 weeks were for ≥ 20% CL reduction (2.98 (95% CI, 1.62–5.49) and 2.89 (95% CI, 1.52–5.57), respectively). Despite significant differences in sensitivity among the different cut‐offs for cervical shortening, favoring the ≥ 10% reduction cut‐off, a reduction of ≥ 20% in CL showed the strongest association with PTD ≤ 34 weeks (odds ratio (OR), 4.11 (95% CI, 1.75–9.62)) and < 37 weeks (OR, 3.62 (95% CI, 1.65–7.96)), as compared with a less pronounced reduction in CL. Conclusions: In women with a short cervix treated with vaginal progesterone, a reduction in CL on a subsequent ultrasound scan can predict PTD ≤ 34 and < 37 weeks. A ≥ 20% reduction in CL had the highest positive likelihood ratio and strongest association with PTD ≤ 34 and < 37 weeks compared with ≥ 10% or ≥ 5 mm reduction. © 2023 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Oestrus is defined as a period when a female animal exhibits characteristic sexual behaviour in the presence of a mature male. Oestrous manifestation in dairy animals is due to the oestrogen (E2) effect on the central nervous system (CNS). It is a critical issue to be considered on a priority basis. Inefficient oestrous detection reduces the fertility status of the herd. The primary and most reliable indicator of oestrus is standing to be mounted by a bull or another female herd mate, signalling receptivity and the pre‐ovulatory state in dairy cattle. Oestrous detection is primarily a management challenge requiring skill and vigilance. To improve the efficiency of oestrous detection in dairy cattle, visual observation is one of the best methods if done three times a day; however, heat detection aids, if combined, give better results. However, techniques like using teaser bulls, tail painting, chin ball markers, ultrasound (USG) examination, hormonal analysis and examination of cervicovaginal mucus (CVM) improve oestrous detection efficiency. Moreover, the changes in production systems have reduced the expression of oestrous behaviour among cows, due to higher oestrogen (E2) metabolism. Therefore, automated systems, such as pedometers, accelerometers and acoustic sensors like infrared thermography (IRT) and image processing, have significantly enhanced reproductive performance by facilitating oestrous detection and optimizing insemination schedules. From this review, we would conclude that oestrous detection alone contributes considerably to the reproductive status of the herd; therefore, applying different methods of oestrous detection reduces the incidence of missed oestrus and improves the fertility status of the herd. [ABSTRACT FROM AUTHOR]

As no study about the combined effect of low levels of Cd2+ with procymidone (PCM) on organs and organisms, we investigated their actions on mouse‐ovary in vivo and in vitro. Four‐week mice were treated with corn oil for the control group, corn oil + 0.0045 mg/L Cd2+ (CdCl2 was dissolved in ultrapure water and freely consumed by mice) for Cd2+ group, 50 mg/kg/d PCM (suspended in corn oil and administered orally to mice) for PCM group, and 50 mg/kg/d PCM + 0.0015 (0.0045 and 0.0135) mg/L Cd2+ for L+ (M+ and H+) PCM group for 21 days. For in vitro experiment, the cultured ovaries were treated with acetone for the control group, 0.1% acetone + 8.4 μg/L Cd2+ for the Cd2+ group, 0.63 mg/L PCM (dissolved in acetone) for the PCM‐group, and 0.63 mg/L PCM + 2.8 (8.4 and 25.2) μg/L Cd2+ for L+ (M+ and H+) PCM group for 7 days. Mouse body weight in each treatment group, the weight and volume of ovaries in all PCM groups were lower than the control. Both in vivo and in vitro, all‐stage follicle numbers were lower in M+PCM and H+PCM groups, whereas the atretic follicles and CASPASE3/8 were higher; meanwhile, lower estradiol and progesterone and higher unfolded protein response (UPR) members in all PCM groups. L+, M+, and H+PCM groups had further ovarian damage and stronger UPR than PCM groups, as did M+PCM groups over Cd2+ groups. It is hypothesized low‐level PCM and Cd2+ may mutually promote each other's triggered UPR and exacerbate ovarian damage. [ABSTRACT FROM AUTHOR]

High fructose intake during pregnancy increases insulin resistance (IR) and gestational diabetes mellitus (GDM) risk. IR during pregnancy primarily results from elevated hormone levels. We aim to determine the role of liver carbohydrate response element binding protein (ChREBP) in insulin sensitivity and lipid metabolism in pregnant mice and their offspring. Pregnant C57BL/6J wild-type mice and hepatocyte-specific ChREBP-deficient mice were fed with a high-fructose diet (HFrD) or normal chow diet (NC) pre-delivery. We found that the combination of HFrD with pregnancy excessively activates hepatic ChREBP, stimulating progesterone synthesis by increasing MTTP expression, which exacerbates IR. Increased progesterone levels upregulated hepatic ChREBP via the progesterone-PPARγ axis. Placental progesterone activated the progesterone-ChREBP loop in female offspring, contributing to IR and lipid accumulation. In normal dietary conditions, hepatic ChREBP modestly affected progesterone production and influenced IR during pregnancy. Our findings reveal the role of hepatic ChREBP in regulating insulin sensitivity and lipid homeostasis in both pregnant mice consuming an HFrD and female offspring, and suggest it as a potential target for managing gestational metabolic disorders, including GDM. Synopsis: Hepatic ChREBP depletion improves insulin resistance and reduces hepatic lipid accumulation in pregnant mice and their female offsprings exposed to a high-fructose diet during pregnancy. Insulin resistance and hepatic steatosis induced by high-fructose diet during pregnancy are associated with overactivation of hepatic ChREBP. Hepatocyte-specific ChREBP depletion improves insulin resistance and inhibits hepatic lipid accumulation in pregnant mice and their female offsprings exposed to a high-fructose diet during pregnancy. Hepatic ChREBP and progesterone form a positive feedback loop involved in regulating high-fructose diet-induced insulin resistance and lipid synthesis during pregnancy. Hepatic ChREBP depletion improves insulin resistance and reduces hepatic lipid accumulation in pregnant mice and their female offsprings exposed to a high-fructose diet during pregnancy. [ABSTRACT FROM AUTHOR]

Aim: The central CO2 chemoreflex is a vital component of respiratory control networks, providing excitatory drive during resting conditions and challenges to blood gas homeostasis. The retrotrapezoid nucleus is a crucial hub for CO2 chemosensitivity; its ablation or inhibition attenuates CO2 chemoreflexes and diminishes restful breathing. Similar phenotypes characterize certain hypoventilation syndromes, suggesting underlying retrotrapezoid nucleus impairment in these disorders. Progesterone stimulates restful breathing and CO2 chemoreflexes. However, its mechanisms and sites of actions remain unknown and the experimental use of synthetic progestins in patients and animal models have been met with mixed respiratory outcomes. Methods: We investigated whether acute or chronic administration of the progestinic drug, etonogestrel, could rescue respiratory chemoreflexes following selective lesion of the retrotrapezoid nucleus with saporin toxin. Adult female Sprague Dawley rats were grouped based on lesion size determined by the number of surviving chemosensitive neurons, and ventilatory responses were measured by whole body plethysmography. Results: Ventilatory responses to hypercapnia (but not hypoxia) were compromised in a lesion‐dependent manner. Chronic etonogestrel treatment improved CO2 chemosensitivity selectively in rats with moderate lesion, suggesting that a residual number of chemosensitive neurons are required for etonogestrel‐induced CO2 chemoreflex recovery. Conclusion: This study provides new evidence for the use of progestins as respiratory stimulants under conditions of central hypoventilation and provides a new testable model for assessing the mechanism of action of progestins in the respiratory network. [ABSTRACT FROM AUTHOR]

Aim: Drospirenone (DRSP) is a synthetic progestogen approved as a progestin‐only pill for contraception in both the United States and Europe. Herein, we conducted a phase I/II study to evaluate the pharmacokinetics, pharmacodynamics, and safety of DRSP in Japanese women. Methods: Single and multiple doses of 4 mg of DRSP were orally administered to healthy premenopausal Japanese women. In the multiple‐dose period, 4 mg of DRSP was administered once daily for 24 days. Pharmacokinetics, hormone levels, and adverse events (AEs) were investigated. Results: Twelve Japanese women participated in this study. The single‐ and multiple‐dose pharmacokinetics of DRSP was similar to that reported in previous studies in Caucasians. In the multiple‐dose period, no subject displayed a progesterone level of more than 5.03 ng/mL. AEs were observed in 11 (91.7%) subjects. The most common AE was genital hemorrhage, which was observed in six (50.0%) subjects, followed by diarrhea and acne in four (33.3%) subjects each. All AEs resolved or improved at the end of the study, and complete recovery was confirmed in all subjects at follow‐up. Conclusions: The pharmacokinetics of DRSP in Japanese women was similar to that of previous studies performed in Caucasian women. Repeated administration of DRSP maintained low plasma progesterone levels indicating effective inhibition of ovulation. No notable safety concerns were observed. In this phase I/II study, DRSP had no obvious pharmacokinetic, pharmacodynamic, or safety issues to consider in Japanese women. [ABSTRACT FROM AUTHOR]

Progesterone (P4), commonly administered in high doses for endometrial cancer palliative management, has limitations in current delivery systems. This preliminary in vitro drug release study introduces electrospun patches to offer a new perspective on P4 delivery. The study aimed to assess the influence of the surfactant polysorbate 80 (PS80) on the release of P4 from polycaprolactone (PCL) fibers. The PS80 effects are examined to inform the fine‐tuning of the fibre generation process. Patches developed, PCL wet (with PS80) and PCL dry (without PS80), showed encapsulation efficiencies of 76% and 42%, respectively. The dose levels studied are 6.1 mg for PCL wet and 4.4 mg for PCL dry samples. Molecular studies show that higher surfactant levels improved P4‐polymer mixing, enhancing dissolution and release rates. Patches with PS80 released 66% of the drug in 17 h, while those without released only 51%. Release data best fit the Weibull model, showcasing promise for these patches in transdermal P4 delivery. This study offers a non‐invasive option compared to traditional methods and underscores the need for further research to confirm the patches' clinical effectiveness for potential use in gynecological oncology. [ABSTRACT FROM AUTHOR]

This article explores the potential of simvastatin (SIM) and mifepristone (MIF) as a combined treatment for uterine fibroids. The study investigates the effects of SIM on the progesterone receptor (PR) pathway and fibroid cell proliferation using human tissue samples, cell cultures, and a xenograft mouse model. The results show that SIM inhibits fibroid growth by suppressing PR expression and downstream signaling pathways. Additionally, the combination of SIM and MIF demonstrates a synergistic effect in inhibiting fibroid cell proliferation and affecting extracellular matrix dynamics. The findings suggest that SIM and MIF may have potential as a multi-pronged treatment for uterine fibroids. [Extracted from the article]

Endometrioid adenocarcinoma (EEC) is one of the most common cancers of the female reproductive system. In recent years, much emphasis has been placed on early diagnosis and treatment. PAX2 (Paired box 2) inactivation is reportedly an important biomarker for endometrioid intraepithelial neoplasia (EIN) and EEC. However, the role of PAX2 in EEC carcinogenesis remains unclear. PAX2 expression and associated clinical characteristics were analyzed via The Cancer Genome Atlas, Gene Expression Omnibus, and Cancer Cell Line Encyclopedia databases and clinical paired EIN/EEC tissue samples. Bioinformatic analysis was conducted to identify the putative molecular function and mechanism of PAX2. Cell proliferation, colony formation, cell migration, and invasion assays in vitro, and mouse xenograft models were utilized to study the biological functions of PAX2 in vivo. Pyrosequencing and the demethylating drug 5‐Aza‐dc were used to verify promoter methylation in clinical tissues and cell lines, respectively. The mechanism underlying the regulatory effect of estrogen (E2) and progesterone (P4) on PAX2 expression was investigated by receptor block assay and double luciferase reporter assay. PAX2 expression was found to be significantly downregulated in EIN and EEC tissues, its overexpression inhibited EEC cell malignant behaviors in vivo and in vitro and inhibited the AKT/mTOR signaling pathway. PAX2 inactivation in EEC was related to promoter methylation, and its expression was regulated by E2 and P4 through their receptors via promoter methylation. Our findings elucidated the expression and function of PAX2 in EEC and have provided hitherto undocumented evidence of the underlying molecular mechanisms. PAX2 expression is suppressed by estrogen prompting its methylation through estrogen receptor. Furthermore, PAX2 regulates the AKT/mTOR signaling pathway to influence EEC progression. © 2024 The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Synthetic progestins in oral contraceptives are thought to blunt heat dissipation by reducing skin blood flow and sweating. However, whether progestin‐releasing intrauterine devices (IUDs) modulate heat loss during exercise‐heat stress is unknown. We used direct calorimetry to measure whole‐body total (dry + evaporative) heat loss in young, physically active women (mean (SD); aged 24 (4) years, V̇O2peak${\dot V_{{{\mathrm{O}}_{\mathrm{2}}}{\mathrm{peak}}}}$ 39.3 (5.3) ml/kg/min) with (IUD; n = 19) and without (Control; n = 17) IUDs in the follicular and luteal phases of the menstrual cycle during light‐ and moderate‐intensity exercise at fixed rates of heat production (∼175 and ∼275 W/m2) in 30°C, ∼21% relative humidity. Between‐group and ‐phase differences were evaluated using traditional hypothesis testing and statistical equivalence testing within pre‐determined bounds (±11 W/m2; difference required to elicit a ±0.3°C difference in core temperature over 1 h) in each exercise bout. Whole‐body total heat loss was statistically equivalent between groups within ±11 W m−2 (IUD–Control [90% CIs]; Light: −2 [−8, 5] W/m2, P = 0.007; Moderate: 0 [−6, 6] W/m2, P = 0.002), as were dry and evaporative heat loss (P ≤ 0.023), except for evaporative heat loss during moderate‐intensity exercise (equivalence: P = 0.063, difference: P = 0.647). Whole‐body total and evaporative heat loss were not different between phases (P ≥ 0.267), but dry heat loss was 3 [95% CIs: 1, 5] W/m2 greater in the luteal phase (P ≤ 0.022). Despite this, all whole‐body heat loss outcomes were equivalent between phases (P ≤ 0.003). These findings expand our understanding of the factors that modulate heat exchange in women and provide valuable mechanistic insight of the role of endogenous and exogenous female sex hormones in thermoregulation. Key points: Progestin released by hormonal intrauterine devices (IUDs) may negatively impact heat dissipation during exercise by blunting skin blood flow and sweating. However, the influence of IUDs on thermoregulation has not previously been assessed.We used direct calorimetry to show that IUD users and non‐users display statistically equivalent whole‐body dry and evaporative heat loss, body heat storage and oesophageal temperature during moderate‐ and high‐intensity exercise in a warm, dry environment, indicating that IUDs do not appear to compromise exercise thermoregulation.However, within IUD users and non‐users, dry heat loss was increased and body heat storage and oesophageal temperature were reduced in the luteal compared to the follicular phase of the menstrual cycle, though these effects were small and unlikely to be practically meaningful.Together, these findings expand our understanding of the factors that modulate heat exchange in women and have important practical implications for the design of future studies of exercise thermoregulation. [ABSTRACT FROM AUTHOR]

Women typically sleep and wake earlier than men and have been shown to have earlier circadian timing relative to the light/dark cycle that synchronizes the clock. A potential mechanism for earlier timing in women is an altered response of the circadian system to evening light. We characterized individual‐level dose–response curves for light‐induced melatonin suppression using a within‐subjects protocol. Fifty‐six participants (29 women, 27 men; aged 18–30 years) were exposed to a range of light illuminances (10, 30, 50, 100, 200, 400, and 2000 lux) using melatonin suppression relative to a dim control (<1 lux) as a marker of light sensitivity. Women were free from hormonal contraception. To examine the potential influence of sex hormones, estradiol and progesterone was examined in women and testosterone was examined in a subset of men. Menstrual phase was monitored using self‐reports and estradiol and progesterone levels. Women exhibited significantly greater melatonin suppression than men under the 400‐lux and 2000‐lux conditions, but not under lower light conditions (10–200 lux). Light sensitivity did not differ by menstrual phase, nor was it associated with levels of estradiol, progesterone, or testosterone, suggesting the sex differences in light sensitivity were not acutely driven by circulating levels of sex hormones. These results suggest that sex differences in circadian timing are not due to differences in the response to dim/moderate light exposures typically experienced in the evening. The finding of increased bright light sensitivity in women suggests that sex differences in circadian timing could plausibly instead be driven by a greater sensitivity to phase‐advancing effects of bright morning light. [ABSTRACT FROM AUTHOR]

Objectives: Ectopic pregnancy (EP) is a major high‐risk outcome following a pregnancy of unknown location (PUL) classification. Biochemical markers are used to triage PUL as high vs low risk to guide appropriate follow‐up. The M6 model is currently the best risk‐prediction model. We aimed to update the M6 model and evaluate whether performance can be improved by including clinical factors. Methods: This prospective cohort study recruited consecutive PUL between January 2015 and January 2017 at eight units (Phase 1), with two centers continuing recruitment between January 2017 and March 2021 (Phase 2). Serum samples were collected routinely and sent for β‐human chorionic gonadotropin (β‐hCG) and progesterone measurement. Clinical factors recorded were maternal age, pain score, bleeding score and history of EP. Based on transvaginal ultrasonography and/or biochemical confirmation during follow‐up, PUL were classified subsequently as failed PUL (FPUL), intrauterine pregnancy (IUP) or EP (including persistent PUL (PPUL)). The M6 models with (M6P) and without (M6NP) progesterone were refitted and extended with clinical factors. Model validation was performed using internal–external cross‐validation (IECV) (Phase 1) and temporal external validation (EV) (Phase 2). Missing values were handled using multiple imputation. Results: Overall, 5473 PUL were recruited over both phases. A total of 709 PUL were excluded because maternal age was < 16 years or initial β‐hCG was ≤ 25 IU/L, leaving 4764 (87%) PUL for analysis (2894 in Phase 1 and 1870 in Phase 2). For the refitted M6P model, the area under the receiver‐operating‐characteristics curve (AUC) for EP/PPUL vs IUP/FPUL was 0.89 for IECV and 0.84–0.88 for EV, with respective sensitivities of 94% and 92–93%. For the refitted M6NP model, the AUCs were 0.85 for IECV and 0.82–0.86 for EV, with respective sensitivities of 92% and 93–94%. Calibration performance was good overall, but with heterogeneity between centers. Net Benefit confirmed clinical utility. The change in AUC when M6P was extended to include maternal age, bleeding score and history of EP was between −0.02 and 0.01, depending on center and phase. The corresponding change in AUC when M6NP was extended was between −0.01 and 0.03. At the 5% threshold to define high risk of EP/PPUL, extending M6P altered sensitivity by −0.02 to −0.01, specificity by 0.03 to 0.04 and Net Benefit by −0.005 to 0.006. Extending M6NP altered sensitivity by −0.03 to −0.01, specificity by 0.05 to 0.07 and Net Benefit by −0.005 to 0.006. Conclusions: The updated M6 model offers accurate diagnostic performance, with excellent sensitivity for EP. Adding clinical factors to the model improved performance in some centers, especially when progesterone levels were not suitable or unavailable. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Urovagina (UV) is less studied in cows. The vaginal contents, constrictor vestibule muscle activity, circulating progesterone, pelvic girdle, vagina and vulva angles were compared on Days 0 and 14 within and between UV (UV group; n = 36) and normal (N group; n = 36) cows. The oestrous duration was compared among the groups. Parameters for various UV severities were also compared. Another set of pregnant‐postpartum cows (P‐PP group; n = 31) underwent monthly evaluations for UV and the angles from the third month of pregnancy until the second month postpartum. The effect of age, parity and body condition score on UV severities on Day 0, and parity on angles in the P‐PP group was evaluated. Different variables were correlated in different groups. The UV group was repeat breeder, exhibited prolonged oestrus and reduced progesterone on Day 14. The latter increased with UV severity on Day 0. On Day 14, severe form of UV was more prevalent. The UV severity increased with parity. In the UV group, a cranioventral pelvic girdle on Day 0 became more cranioventral on Day 14 and was correlated with the vagina moving from a caudodorsal position on Day 0 to a cranioventral position on Day 14. In the P‐PP group, the pelvic girdle and vagina remained caudodorsal and UV was undetectable throughout the study. Vagina and vulva displayed a parity‐by‐month interaction in the P‐PP group. To summarize, the UV characteristics were influenced by the oestrous cycle stage, pelvic girdle angles, and parity. [ABSTRACT FROM AUTHOR]

This study evaluated the efficacy of the administration of different doses of equine chorionic gonadotropin (eCG; 0 IU, 200 IU, or 300 IU) at the time of the progesterone device removal in 2‐year‐old Nelore (Bos indicus) heifers synchronized for fixed‐timed artificial insemination (FTAI). On day 0 (D0), a total of 398 heifers received 2 mg of oestradiol benzoate i.m., 0.53 mg of cloprostenol i.m., and an eight‐day previously used (second use) intravaginal device containing 1 g of progesterone (P4). Eight days later (D8), simultaneous with the P4 device removal, 0.5 mg of oestradiol cypionate i.m. and 0.53 mg of cloprostenol i.m. were administered. At the same time, heifers were randomly assigned to receive one of the following treatments: G‐0 IU (n = 141; no eCG treatment), G‐200 IU (n = 132; treated with 200 IU of eCG), and G‐300 IU (n = 125; treated with 300 IU of eCG). FTAI was performed 48 h after the P4 device removal (D10). Ultrasonographic evaluations were performed at D0, D10, and D17. Heifers were scanned to measure the size of the largest follicle (LF), the presence, number, and size of the corpus luteum (CL), and the ovulation rate. Subsequently, at D40, the heifers underwent scanning to determine the pregnancy rate and identify any twin pregnancies. Additionally, at D70, scans were performed to assess pregnancy loss (PG). Data were analysed by orthogonal contrasts [C1 (eCG effect): control x (200 IU + 300 IU) and C2 (eCG dose effect): 200 IU × 300 IU]. On D0, CL presence was similar between the groups [G‐0 IU = 65.2% (92/141), G‐200 IU = 55.3% (73/132), and G‐300 IU = 63.2% (79/125); p =.16]. No interactions between the presence of CL on D0 and eCG treatment were found for any of the variables (p >.05). The diameter of the LF at FTAI (D10) was not influenced by eCG treatment (p =.22) or eCG dose (p =.18). However, treatment with eCG increased the diameter of the CL at D17 (G‐0 IU = 15.7 ± 0.3 mmb, G‐200 IU = 16.6 ± 0.2 mma, and G‐300 IU = 16.6 ± 0.3 mma; p =.001), regardless of the dose used (p =.94). The ovulation rate was higher in heifers treated with eCG [G‐0 IU = 79.4%b (112/141), G‐200 IU = 90.2%a (119/132), and G‐300 IU = 93.6%a (117/125); p =.002], but there was no effect of eCG dose (p =.36). Pregnancy per AI (P/AI) on D40 [G‐0 IU = 32.6%b (46/141), G‐200 IU = 42.4%a (56/132), and G‐300 IU = 42.4%a (53/125); P = 0.05] and D70 [G‐0 IU = 29.1%b (41/141), G‐200 IU = 40.9%a (54/132), and G‐300 IU = 40.8%a (51/125); p =.02] were higher on heifers that received eCG; however, no dose effect was observed for P/AI on D40 (p =.89) nor D70 (p =.98). Pregnancy loss between D40 and D70 tended to reduce (p =.07) in eCG‐treated heifers without dose effect (p =.91). Heifers with CL at D0 presented a greater follicle diameter (LF) on D10 (With CL = 11.2 ± 0.2 mm and Without CL = 10.2 ± 0.2 mm; p =.05), CL diameter on D17 (With CL = 15.8 ± 0.03 mm and Without CL = 11.8 ± 0.6 mm; p =.01), and ovulation rate [With CL = 95.5% (233/244) and Without CL = 74.7% (115/154); p =.01]. However, no difference in pregnancy rate at D40 (p =.52) and D70 (p =.84) was found. In conclusion, eCG treatment increases ovulation and pregnancy rates of heifers submitted to a FTAI protocol. Furthermore, eCG treatment increases the diameter of the CL after FTAI and reduces pregnancy losses. No dose effect was observed, suggesting Nelore (Bos indicus) heifers respond to 200 IU of eCG treatment for FTAI. [ABSTRACT FROM AUTHOR]

This study investigated the effect of human menopausal gonadotropin (hMG) on reproductive efficiency of synchronized ewes with the sponge and progesterone (P4) injection‐based protocols. In study 1, anoestrous ewes (n = 120) were used. Sixty ewes were treated with sponge (S) for 12 days. The injection of eCG (SeCG group, n = 30) or hMG (ShMG, n = 30) was given at the time of sponge removal. Thirty ewes received IM injection of P4, three times every 48 h and the injection of hMG was given 24 h after the third P4 injection (3PhMG group, n = 30), and 30 ewes were used as control group. Pregnancy was diagnosed on day 50 after the release of ram. In study 2, 60 ewes were randomly divided into two equal groups. In the treated group with antibiotics (n = 30), before inserting, the sponges were impregnated with the antibiotic penicillin G sodium (5,000,000 IU) and in the control group (n = 30), there was no added antibiotics. Before inserting and after removing sponges, a vaginal cytology sample was taken with a sterile cotton swab. The number of neutrophils in each sample was counted and analysed. The rate of oestrus and total pregnancy was greater in SeCG (96.7, 93.3%), ShMG (82.8, 93.1%) and 3PhMG (67.9, 89.3%) groups compared with the control group (13.8, 41.4%) (p <.05). No significant difference was found in single, twin and total lambing and pregnancy rates after injection of eCG and hMG during the non‐breeding season (p >.05). A higher percentage of control ewes had the vaginal smear with neutrophils more than 50% (96.7% vs. 76.7%; p <.05). In conclusion, a single dose of hMG can induce fertile oestrus in synchronized ewes with P4 administered by either injection or intravaginally. Purulent discharge and percentage of neutrophils were significantly reduced in the synchronized ewes by the impregnated sponges with the antibiotic penicillin. [ABSTRACT FROM AUTHOR]

Aim: This pilot study aimed to assess the utility of an oral progesterone treatment protocol for women who commenced medical abortion and then changed their mind and wished instead to maintain their pregnancy. Methods: The Progesterone‐After‐Mifepristone—pilot for efficacy and reproducibility (PAMper) trial was designed as a prospective single‐arm pilot clinical trial, conducted via telehealth. Women aged 18 to 45 years in Australia who reported ingesting mifepristone within the last 72 h to initiate medical abortion and had not taken misoprostol were included. Initial contact was by a web‐based form. Following informed consent, participants were prescribed oral progesterone to be taken 400 mg twice per day for 3 days then 400 mg at night until completion of a 19 day course. Pregnancy viability was assessed by ultrasound scan after 14 days of progesterone treatment. Results: Between October 2020 and June 2021, nine women contacted the PAMper trial, of whom six enrolled and commenced progesterone treatment. These women reported ingesting mifepristone at 40–70 days of gestation, with progesterone being commenced within 5.7–72 h of mifepristone ingestion. Five participants had ongoing, live pregnancies at the primary endpoint (ultrasound at >2 weeks). One participant had a miscarriage after 9 days of progesterone treatment. There were no clinically significant adverse events. Conclusion: This small study demonstrated a clinically sound protocol for researching the use of progesterone‐after‐mifepristone for women in this circumstance. Results of this pilot study support the need for further larger scale trials in this field. [ABSTRACT FROM AUTHOR]

There is significant variation in practice when managing couples with recurrent miscarriage (RM), with guidelines differing on the definition of RM, recommended investigations, and treatment options. In the absence of evidence‐based guidance, and following on from a paper by the authors—FIGO Good Practice Recommendations on the use of progesterone in the management of recurrent first‐trimester miscarriage—this narrative review aims to propose a global holistic approach. We present graded recommendations based on best available evidence. Synopsis: Best practice recommendations for managing couples with recurrent miscarriage. [ABSTRACT FROM AUTHOR]

Follicle selection in hens refers to a biological process that only one small yellow follicle (SYF) is selected daily or near‐daily for following hierarchical development (from F5/F6 to F1) until ovulation. MFN2 is a kind of GTPases located on the mitochondrial outer membrane, which plays a crucial role in mitochondrial fusion. This study aimed to elucidate the role of MFN2 in proliferation and progesterone biosynthesis of granulosa cells (GCs) during follicle selection in hens. The results showed that GCs began to produce progesterone (P4) after follicle selection, accompanied with changes from multi‐layer with flat cells to single layer with cubic cells. MFN2 was detected in GCs of follicles from SYF to F1. After follicle selection, the expression level of MFN2 in GCs upregulated significantly, accompanied with increases in P4 biosynthesis, ATP production, mitochondrial DNA (mtDNA) copy numbers of granulosa cells. FSH (80 ng/mL) facilitated the effects of P4 biosynthesis and secretion, ATP production, mtDNA copy numbers, cell proliferation and the MFN2 transcription of granulosa cells from F5 (F5G) in vitro. However, FSH treatment did not promote P4 secretion in granulosa cells from SYF (SYFG) in vitro. Meanwhile, we observed that change fold of MFN2 transcription, ATP production, mtDNA copy numbers and cell proliferation rate in F5G after treatment with FSH were greater than those in SYFG. Furthermore, expression levels of MFN2 protein and messenger RNA in F5G were significantly higher than those in SYFG after treatment with FSH. P4 biosynthesis, ATP production, mtDNA copy numbers as well as cell proliferation reduced significantly in F5G with MFN2 knockdown. Oppositely, P4 biosynthesis, ATP production, mtDNA copy numbers and cell proliferation increased significantly in SYFG after the overexpression of MFN2. Our results suggest that the upregulation of MFN2 may be involved in the initiation of P4 biosynthesis, and promotion of GCs proliferation during follicle selection. [ABSTRACT FROM AUTHOR]

Background: Several variables influence the serum concentration of thyroid hormones in dogs, including breed, age, drugs, and concurrent diseases. However, data regarding the interaction between thyroid function and the estrous stage of female dogs are limited. Hypothesis: Estrous stage may influence thyroid function in German Shepherd dogs. Methods: Longitudinal, observational, non‐randomized cohort study. The dogs were monitored during the complete estrous cycle, and different stages were determined by vaginal cytology. Two blood samples were collected at the beginning and end of each stage to analyze the following: total thyroxine (TT4), free thyroxine (fT4), total triiodothyronine (TT3), free triiodothyronine (fT3), canine thyrotropin (cTSH), progesterone, 17‐β‐estradiol, triglycerides, and cholesterol concentrations. Hematological and biochemical evaluations were performed at the beginning and end of the study period. Animals: Seventeen German Shepherds were included, of which 7 were bred during the study period. One dog was excluded for estrus interruption and another for suspected hypothyroidism. Results: Serum concentrations of T4, fT4, and fT3 were negatively correlated with age. Total thyroxine demonstrated significant changes in serum concentrations between estrous stages, with higher concentrations in estrus and diestrus. Total thyroxine concentrations were positively correlated with progesterone concentrations and negatively correlated with 17‐β‐estradiol concentrations. Free thyroxine did not show significant variations but was positively correlated with progesterone concentrations. Canine TSH concentrations were positively correlated with 17‐β‐estradiol concentrations. No significant differences in thyroid hormones and cTSH concentrations were observed between diestrus during pregnancy and pseudopregnancy. Conclusions: Different stages of estrus can influence the measurement of TT4 in female dogs. [ABSTRACT FROM AUTHOR]

Decidualization of endometrial stroma is a key step in embryo implantation and its abnormality often leads to pregnancy failure. Stromal decidualization is a very complex process that is co‐regulated by estrogen, progesterone and many local factors. The signaling protein SHP2 encoded by PTPN11 is dynamically expressed in decidualized endometrial stroma and mediates and integrates various signals to govern the decidualization. In the present study, we investigate the mechanism of PTPN11 gene transcription. Estrogen, progesterone and cAMP co‐induced decidualization of human endometrial stromal cell in vitro, but only progesterone and cAMP induced SHP2 expression. Using the luciferase reporter, we refined a region from −229 bp to +1 bp in the PTPN11 gene promoter comprising the transcriptional core regions that respond to progesterone and cAMP. Progesterone receptor (PGR) and cAMP‐responsive element‐binding protein 1 (CREB1) were predicted to be transcription factors in this core region by bioinformatic methods. The direct binding of PGR and CREB1 on the PTPN11 promoter was confirmed by electrophoretic mobility and chromatin immunoprecipitation in vitro. Knockdown of PGR and CREB1 protein significantly inhibited the expression of SHP2 induced by medroxyprogesterone acetate and cAMP. These results demonstrate that transcription factors PGR and CREB1 bind to the PTPN11 promoter to regulate the expression of SHP2 in response to decidual signals. Our results explain the transcriptional expression mechanism of SHP2 during decidualization and promote the understanding of the mechanism of decidualization of stromal cells. [ABSTRACT FROM AUTHOR]

This study examined the impact of cyclicity (with or without cycle corpus luteum; CL) on oocyte quality and embryonic development in buffaloes. We collected oocytes from the ovaries of slaughtered buffaloes (N = 158 cyclic; n = 316 ovaries and N = 177 acyclic; n = 353 ovaries). Blood progesterone concentration and number of oocytes per ovary were higher in cyclic buffaloes. Cyclic buffalo ovaries produce higher oocytes with I + II and fewer III + IV grades. Oocytes from cyclic buffaloes had a higher maturation rate based on cumulus expansion, cleavage rate and embryo development to the 8‐cell, morula and blastocyst stages than acyclic buffaloes. In conclusion, oocytes recovered from the ovaries of the cyclic buffaloes showed improved oocyte competence and subsequent in vitro blastocyst development. [ABSTRACT FROM AUTHOR]

We tested in the present study the hypothesis that supplementation with long‐acting P4 (iP4) at different times of the initial dioestrus improves pregnancy rates in dairy and beef recipients submitted to fixed‐time embryo transfer (FTET). Recipients from commercial farms had their oestrous cycle synchronized with an E2/P4‐based protocol in three experiments (Exp. 1 to 3). In Exp. 1, dairy heifers (n = 76) and cows (n = 104) were randomly assigned to two experimental groups: the control group (n = 89) and the iP4D4 group (n = 91). For Exps. 2 and 3, suckled beef recipients were used. In Exp. 2, recipients were assigned to two experimental groups: Control group (n = 147) and iP4D7 group (n = 144); whereas in Exp. 3, recipients were randomly assigned to three experimental groups: Control group (n = 85), iP4‐D4 group (n = 86) and iP4D7 group (n = 81). Recipients in the iP4D4 and iP4‐D7 groups received an i.m. administration of 150 mg iP4, on D4 or D7 (D0 was the day of expected oestrus). On D7, all recipients were evaluated by transrectal ultrasonography and those that had a CL received a fresh or vitrified in vitro‐produced embryo. In Exp. 2 and 3, the CL area was also determined by ultrasonography at the time of FTET. The pregnancy diagnosis was performed at 30 days in Exp. 1, 57 days in Exp. 2, and between 40 and 72 days of pregnancy in Exp. 3. In Exp. 1, the pregnancy rate did not differ (p >.1) between the Control group (38.2% [34/89]) and iP4D4 group (49.5% [45/91]); yet, a parity effect indicated a greater (p <.05) pregnancy rate in heifers (57.9% [44/76]) than cows (30.8% [32/104]). In Exp. 2, the pregnancy rate was greater (p <.05) in the iP4D7 group (45.0% [65/144]) than in the Control group (34.0% [50/147]). Also, a greater (p =.08) pregnancy rate was observed for recipients with a small CL (≤2.75 cm2) that were treated with iP4 on the day of FTET than the control recipients (46.4% [32/69] vs. 32.6% [28/86]). In Exp. 3, no significant effects (p >.1) of the treatment group or CL size were detected on pregnancy rates at days 30 and 60. In conclusion, the beneficial effects of iP4 supplementation at early dioestrus on pregnancy maintenance may vary according to the experimental conditions, but its use at the time of FTET can be used as an alternative to enhance the fertility of beef recipients in challenging conditions in commercial herds. [ABSTRACT FROM AUTHOR]

Azoospermia is a severe problem that prevents couples from having their own children through natural pregnancy. In nonobstructive azoospermia (NOA), microdissection testicular sperm extraction (micro-TESE) is required to collect sperm and, at 40%–60%, the sperm retrieval success rate is not very high. Previous studies identified no single clinical finding or investigation that could accurately predict the outcome of sperm retrieval. It would be very valuable to have a factor for predicting the possibility of sperm retrieval in patients with NOA before performing micro-TESE. We retrospectively obtained data from the medical records of 430 patients who underwent micro-TESE from 2011 to 2020. Parameters extracted were age, height, body weight, body mass index, luteal hormone, follicle-stimulating hormone, PRL, total testosterone, E2, T/E2, sperm retrieval, G-band, AZF, medical history, Rt testis, and Lt testis. Prediction One, which does not require coding, was used to create the AI prediction model for sperm retrieval. Prediction One makes the best prediction model using an artificial neural network with internal cross-validation. Prediction One also evaluates the "importance of variables" using a method based on permutation feature importance. The AUC for the AI model was 0.7246, which is acceptable. In addition, among the variables, T/E2 ratios contributed most to predicting whether sperm retrieval was possible or not. However, the difference in T/E2 between successful and unsuccessful sperm retrieval was not statistically significant. In addition, our analysis of data from 20 patients who underwent micro-TESE in 2021 found that in 85%, the actual result matched the result predicted using our novel AI model. We created an AI model for predicting sperm retrieval in patients with NOA before undergoing micro-TESE. In addition, we found that T/E2 ratios contributed most to predicting possibility of sperm retrieval in NOA using machine learning. [ABSTRACT FROM AUTHOR]