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Cyclic fluctuations in hypothalamic-pituitary-gonadal axis (HPG-axis) hormones exert powerful behavioral, structural, and functional effects through actions on the mammalian central nervous system. Yet, very little is known about how these fluctuations alter the structural nodes and information highways of the human brain. In a study of 30 naturally cycling women, we employed multidimensional diffusion and T1-weighted imaging during three estimated menstrual cycle phases (menses, ovulation, and mid-luteal) to investigate whether HPG-axis hormone concentrations co-fluctuate with alterations in white matter (WM) microstructure, cortical thickness (CT), and brain volume. Across the whole brain, 17β-estradiol and luteinizing hormone (LH) concentrations were directly proportional to diffusion anisotropy (μFA; 17β-estradiol: β1 = 0.145, highest density interval (HDI) = [0.211, 0.4]; LH: β1 = 0.111, HDI = [0.157, 0.364]), while follicle-stimulating hormone (FSH) was directly proportional to CT (β1 = 0 .162, HDI = [0.115, 0.678]). Within several individual regions, FSH and progesterone demonstrated opposing relationships with mean diffusivity (Diso) and CT. These regions mainly reside within the temporal and occipital lobes, with functional implications for the limbic and visual systems. Finally, progesterone was associated with increased tissue (β1 = 0.66, HDI = [0.607, 15.845]) and decreased cerebrospinal fluid (CSF; β1 = -0.749, HDI = [-11.604, -0.903]) volumes, with total brain volume remaining unchanged. These results are the first to report simultaneous brain-wide changes in human WM microstructure and CT coinciding with menstrual cycle-driven hormone rhythms. Effects were observed in both classically known HPG-axis receptor-dense regions (medial temporal lobe, prefrontal cortex) and in other regions located across frontal, occipital, temporal, and parietal lobes. Our results suggest that HPG-axis hormone fluctuations may have significant structural impacts across the entire brain.

ConspectusBase excision repair (BER) enzymes are genomic superheroes that stealthily and accurately identify and remove chemically modified DNA bases. DNA base modifications erode the informational content of DNA and underlie many disease phenotypes, most conspicuously, cancer. The OG of oxidative base damage, 8-oxo-7,8-dihydroguanine (OG), is particularly insidious due to its miscoding ability that leads to the formation of rare, pro-mutagenic OG:A mismatches. Thwarting mutagenesis relies on the capture of OG:A mismatches prior to DNA replication and removal of the mis-inserted adenine by MutY glycosylases to initiate BER. The threat of OG and the importance of its repair are underscored by the association between inherited dysfunctional variants of the MutY human homologue (MUTYH) and colorectal cancer, known as MUTYH-associated polyposis (MAP). Our functional studies of the two founder MUTYH variants revealed that both have compromised activity and a reduced affinity for OG:A mismatches. Indeed, these studies underscored the challenge of the recognition of OG:A mismatches that are only subtly structurally different than T:A base pairs. Since the original discovery of MAP, many MUTYH variants have been reported, with most considered to be variants of uncertain significance. To reveal features associated with damage recognition and adenine excision by MutY and MUTYH, we have developed a multipronged chemical biology approach combining enzyme kinetics, X-ray crystallography, single-molecule visualization, and cellular repair assays. In this review, we highlight recent work in our laboratory where we defined MutY structure-activity relationship (SAR) studies using synthetic analogs of OG and A in cellular and in vitro assays. Our studies revealed the 2-amino group of OG as the key distinguishing feature of OG:A mismatches. Indeed, the unique position of the 2-amino group in the major groove of OGsyn:Aanti mismatches provides a means for its rapid detection among a large excess of highly abundant and structurally similar canonical base pairs. Furthermore, site-directed mutagenesis and structural analysis showed that a conserved C-terminal domain β-hairpin FSH loop is critical for OG recognition with the His serving as the lesion detector. Notably, MUTYH variants located within and near the FSH loop have been associated with different forms of cancer. Uncovering the role(s) of this loop in lesion recognition provided a detailed understanding of the search and repair process of MutY. Such insights are also useful to identify mutational hotspots and pathogenic variants, which may improve the ability of physicians to diagnose the likelihood of disease onset and prognosis. The critical importance of the FSH loop in lesion detection suggests that it may serve as a unique locus for targeting probes or inhibitors of MutY/MUTYH to provide new chemical biology tools and avenues for therapeutic development.

Purpose: We aimed to investigate the relationship between follicle stimulating hormone (FSH) and inhibin B (InhB). Materials and Methods: Data from 1,230 consecutive men presenting for primary couple’s infertility were analyzed. Healthsignificant comorbidities were scored with Charlson comorbidity index. Quartiles of FSH and InhB were considered to determine threshold values. Descriptive statistics and logistic regression models tested association between FSH and InhB values. Results: Overall, 1,080 (87.8%) men had concordant FSH and InhB values. Conversely, 150 patients (12.2%) had discrepancies in FSH and InhB, with 78 (6.3%) and 72 (5.9%) men reporting both low and high FSH and InhB values, respectively. Infertile men with discordant values were younger (median [interquartile range] 38.0 years [34–41 years] vs. 36.0 years [31–40 years]); had smaller testicular volume (TV) (12 mL [10–15 mL] vs. 15 mL [12–20 mL]); and, had more frequently a sperm DNA fragmentation test >30% (179 [59.1%] vs. 40 [78.4%]) than those with concordant values (all p<0.05). Moreover, a higher frequency of previous cryptorchidism (27.3% vs. 11.9%), lower sperm concentration (3.0 million/mL [0.9–11.0 million/ mL] vs. 13.8 million/mL [3.1–36.0 million/mL]), lower progressive sperm motility rates (12.0% [5.0%–25.3%] vs. 20.0% [7.0%–36.0%]), and greater rates of non-obstructive azoospermia (36.4% vs. 23.9%) were found in men with discordant FSH and InhB values (all p≤0.005). At multivariable logistic regression analysis, higher body mass index (odds ratio [OR], 1.08; p=0.001), smaller TV (OR, 0.91; p<0.001), and a history of cryptorchidism (OR, 2.49; p<0.001) were associated with discordant FSH and InhB values. Conclusions: More than one out of ten infertile men had discordant FSH and InhB values in the real-life setting showing worse clinical profiles than those with concordant levels. Smaller TV and history of cryptorchidism could be used as clinical markers to better tailor the need to test InhB. [ABSTRACT FROM AUTHOR]

Background: Female infertility is partly due to reproductive hormone deregulation, involving the hypothalamic-pituitary-gonadal axis. A high prevalence of female infertility has been reported in the Southwest region of Cameroon, however, little attention has been paid to the hormonal contribution. Objective: This study reports on the implication of hormones in female infertility in two regional hospitals in the Southwest Region of Cameroon. Methods: A hospital-based case-control study was conducted in Buea and Limbe regional hospitals. Cases (n = 86), and controls (n = 40), comprising menstruating and breastfeeding mothers were enrolled from the infertility clinics and vaccination units respectively. A questionnaire was used to collect socio-demographic data and infertility risk factors. Serum follicle stimulating hormone (FSH), luteinizing hormone (LH) and oestradiol were measured on days 1-3 and progesterone on days 21-22 of the menstrual cycle, using ELISA method. Data were analysed using Mann Whitney U-rank, Chi-square tests and multiple logistic regression with p < 0.05 considered significant. Results: Most of the women (57 %) were aged between 26 and 35, and overweight or obese (77 %). Mann Whitney test showed a significant increase in FSH (12.47±5.57 IU/L) for cases than (8.88± 1.50 IU/L) controls (p = 0.001), a significant decrease in LH (6.55±7.19 IU/L) for cases than controls (9.57±2.75 IU/L), (p = 0.001), contrasted by a significant decrease in progesterone (13.48±5.89 ng/mL) for cases compared to controls (6.63±7.23 ng/mL), (p = 0.001). Oestradiol was not statistically significant (p = 0.573). Age of participant and age at menarche were the only statistically significant (p = 0.001), risk factors for infertility. Conclusion: This study revealed that high follicle stimulating hormone and low progesterone are the primary hormonal abnormalities likely to be responsible for female fertility in the study area which were associated with increase in age and age at menarche. [ABSTRACT FROM AUTHOR]

Women with PCOS often experience significant difficulties in achieving spontaneous pregnancy. Intracytoplasmic sperm injection (ICSI) is a viable treatment option for these patients, offering an acceptable success rate. This study purposes to identify factors that may positively or negatively influence pregnancy rates in PCOS women undergoing ICSI and explore potential modifications to enhance successful pregnancy outcomes. The study included ninety sub-fertile couples with female partners with diagnosed PCOS. Comprehensive evaluations of the partners included medical history, physical examination, hormonal analysis, transvaginal ultrasound (TVUS), and seminal fluid analysis. All couples underwent ICSI. Pregnancy rates were determined by positive pregnancy tests 14 days after fresh embryo transfer, and participants were divided into two groups: pregnant and non-pregnant. Of the 90 women who underwent ICSI cycles, 24 achieved pregnancies, resulting in a pregnancy rate of 26.66 %. Non-pregnant women had significantly higher body mass indices (BMI). Additionally, women with elevated cycle day 2 serum estradiol (E2) levels and low follicle-stimulating hormone (FSH) levels exhibited significantly lower pregnancy rates. Women whose male partners had abnormal semen parameters also demonstrated significantly lower pregnancy rates. Several factors negatively impact pregnancy rates in PCOS women undergoing ICSI, including high BMI, elevated E2, low FSH levels on cycle day 2, a lower number of mature oocytes, and male factor sub-fertility. Many of these factors can be mitigated through the use of ICSI, thereby improving the chances of achieving a successful pregnancy. [ABSTRACT FROM AUTHOR]

Objective: Reproductive hormones might impact disease course in cognitive decline. We examined the association between male and female endogenous reproductive hormones and subjective cognitive decline (SCD) score. Design, Patients and Measurements: A cross‐sectional study design was used with baseline data from the Pingyin cohort study, involving 1943 participants aged 45–70 years. Oestrogen (E2), testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) were measured in females and E2 and testosterone were measured in males. We categorised hormones into three levels of low, intermediate and high level. The 9‐item subjective cognitive decline questionnaire (SCD‐Q9) scores were collected to assess the symptoms of SCD. Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% confidence interval (CI) between categorised hormone levels and SCD status. Multivariable linear regression models were also used. Results: Overall, 1943 participants were involved and 1285 (66.1%) were female. The mean age at baseline was 59.1 (standard deviation 7.1) years. Women with high testosterone levels had a higher probability of having SCD compared with those with low testosterone levels (OR 1.43, 95% CI 1.01–2.05). Men with a high level of testosterone (0.59, 0.35–0.98) and high testosterone/E2 ratio (0.55, 0.33–0.90) were related to decreased chances of having SCD. Each one‐unit increase of testosterone was linked to reduced SCD score in males [(β: −.029, 95% CI (−0.052, −0.007)]. Conclusion: There was sex‐specific relationship between hormone levels and SCD abnormal. Those with higher testosterone levels in females may increase likelihood of experiencing SCD. Males with higher testosterone levels and higher testosterone/E2 ratio may be associated with reduced likelihood of SCD. The roles of endogenous reproductive hormone levels and their dynamic changes in cognitive function need further investigation. [ABSTRACT FROM AUTHOR]

Background & Objectives: The relationship of Vitamin-D (VD) with Luteinizing Hormone (LH), Follicle stimulating Hormone (FSH) and Anti Mullerian Hormone (AMH) is recognized. This study was conducted to determine whether VD is a predictor of fertility and investigate its relationship with female reproductive hormones and markers of ovarian reserve in female population of Karachi. Methods: A cross-sectional study was performed from July 2020 to June 2022 at the Aga Khan University Hospital (AKUH) with recruitment of 135 fertile and infertile subjects. VD, AMH, FSH and LH levels were estimated by 'Enzyme Linked Immunosorbent assay (ELISA)'. By applying binary logistic regression, variables with p-value < 0.25 in univariate analysis were used for multivariate regression model and adjusted odds ratios were computed. In multivariate analysis, significance was p-value ≤ 0.05. Results: VD deficiency was observed in all infertile female subjects. In univariate regression analysis, FSH, LH, LH/ FSH ratio and VD levels turned out to be significant. The Multivariate analysis represented that for every one ng/mL increase in VD level, the odds of fertility were expected to be 50.154 times higher with p-value < 0.001. The positive correlation of VD with FSH was significant. Conclusion: VD deficiency was prevalent in all infertile female subjects. VD levels were strong predictor of fertility in the study population. The significant association of VD with FSH explained the indirect effect of VD on follicular development and ovarian functions however no relationship of VD with ovarian reserve was exhibited. [ABSTRACT FROM AUTHOR]

Background. Polycystic Ovary Syndrome (PCOS) is a hormonal disorder affec­ting women of reproductive age. Alarmingly, there is a significant diagnostic gap, with about 75 % of women in hospital settings unknowingly having PCOS due to inconsistent diagnostic criteria. The manifestations of PCOS are multifaceted, along with hyperandrogenism, which results in excessive male hormones, hirsutism, and irregular menstrual cycles, frequently culminating in infertility and profound mental fitness challenges. The role of oxidative stress cannot be understated; it detrimentally influences the reproductive lifespan and inflicts damage that exacerbates infertility issues. Materials and Methods. The research was conducted on 80 women between the ages of 25–45 years who were divided into PCOS and control groups. Women’s blood samples were obtained from the Nineveh Health Directorate Oncology and Nuclear Medicine Hospital, Iraq. The levels of AMH and FSH were measured through the ELISA kits. In addition, biochemical parameters such as glucose, total cholesterol, malondial­dehyde (MDA), and glutathione (GSH) were quantified in both control and PCOS women. Relationships between these variables were explored using unpaired t-tests, Pearson’s correlation coefficient, and multiple of regression analysis. Results and Discussion. FSH levels were positively correlated with age while AMH was related to age inversely, suggesting that aging decreases ovarian reserve in PCOS women. Furthermore, a significant increase in mean serum Malondialdehyde (MDA) was observed for the women with PCOS group compared to healthy controls, aligning with a significant association among AMH and MDA. Remarkably, no statistically significant correlation between FSH and AMH was found relating glucose, and total cholesterol (TC) in the PCOS group. Therefore, the monitoring of these indicators could enhance the clinical care of PCOS. Conclusion. This study reveals age-associated adjustments in ovarian reserve in PCOS. Moreover, the increase in MDA levels revealed the increased oxidative stress that characterized the condition’s complexity.

Objective: We analyze the characteristics and related factors of human chorionic gonadotropin (hCG) of pituitary origin to establish the reference interval to resolve clinical confusion and avoid harmful therapy to Chinese postmenopausal women with “positive” hCG. Materials and methods: This retrospective cohort study identified individuals who underwent hCG measurements at an academic hospital. Three gonadotropins (hCG, follicle stimulating hormone (FSH), and luteinizing hormone (LH)) was drawn from medical records. The age-stratified analyses were performed first. Then the correlations of hCG and FSH, LH as well as age were analysed. Finally, characteristics and associations of hCG, LH, and FSH were evaluated to identify pituitary hCG in postmenopausal women in clinical settings. Results: In total, 9796 cases from 11172 records met inclusion criteria and contributed 9796 hCG, 7541 FSH, and 7536 LH values. The upper reference interval for our cohorts was 5.3 IU/L. HCG, FSH, and LH concentration had no significant correlations with age. HCG moderately correlated with FSH (r = 0.47) and LH level (r = 0.53). However, it was FSH but not LH that manifested good clinical applicability. Conclusion: The prevalence of hCG≥5.0 IU/L and 5.3 IU/L in women ≥55 years is 2.8% and 2.3% in the study population from China. The level of hCG 5.3 IU/L was suggested to be the positive threshold for postmenopausal women. FSH≥40IU/L helps to distinguish the pituitary source of hCG in postmenopausal women whose serum hCG concentrations were between 5.3 and 16 IU/L.

Assisted reproduction is a key aspect of modern animal breeding, providing valuable assistance in improving breeding programs. In this field, the administration of exogenous hormones, such as follicle-stimulating hormone (FSH), plays a crucial role in the induction of multiple ovulations. However, commercial FSH used in veterinary practice has been derived primarily from pituitary glands, obtained mostly from pigs for nearly four decades. Although these hormones have contributed significantly to the advancement of assisted reproductive techniques, they have certain limitations that warrant further improvements. These limitations include contamination with luteinizing hormone (LH), the potential risk of pathogen contamination, the potential to trigger an immune response in non-pig species, and the short half-life in circulation, requiring the implementation of complex 8-dose superovulation schedules. Our research team has developed and characterized a new variant of bovine follicle-stimulating hormone (bscrFSH) to address these limitations. The new hormone is produced recombinantly in CHO cell cultures, with a specific productivity of about 30 pg/cell/day. The bscrFSH can be purified to a high purity of 97 % using a single step of immobilized metal affinity chromatography (IMAC). N-glycan analysis of bscrFSH showed that approximately 74 % of the glycans corresponded to charged structures, including mono-, di-, tri-, and tetra-sialylated glycans. Superovulation trials conducted in cattle revealed that bscrFSH, administered at a total dose of about 0.5 μg per kg of body weight, using a decrescent schedule of 4 doses with 24-h intervals, resulted in an average yield of 8–12 transferable embryos per animal. Further research is required; however, the preliminary findings indicate that bscrFSH, currently packaged under the provisional brand name of Cebitropin B, holds potential as a commercial product for assisted reproduction in ruminants. • The bovine FSH variant (brscFSH) designed by the team is functional in inducing superovulation in cattle. • brscFSH can be produced at 30 pg/cell/day and purified to >95% purity using immobilized-metal affinity chromatography (IMAC). • brscFSH yields 8–12 transferable embryos on average at 0.5 μg/kg in a four-dose schedule over 12 hours. • Further studies are needed to assess brscFSH in two/single-dose schedules and in other species like sheep, goats, camelids, and mares. • brscFSH is now available for research use only on the Centro de Biotecnología y Biomedicina SpA website. [ABSTRACT FROM AUTHOR]

Current infertility treatment practices are shifting from standardized to personalized Follicle Stimulating Hormone (FSH) dosing, with new FSH preparations incorporating individualized dosing in their clinical development. The commonly used regimens include recombinant FSH combined with human menopausal gonadotropin. This study aims to examine the effects of follitropin alpha and follitropin delta on ovarian stimulation, specifically focusing on embryo development and quality of In Vitro Fertilization (IVF) cycles. This cross-sectional was held at Dr. Kariadi Central General Hospital from January 2022 to June 2024. All cycles involved controlled ovarian stimulation using recombinant FSH with either a Gonadotropin Releasing Hormone (GnRH) antagonist, long GnRH agonist or flare GnRH agonist protocols. This study includes patients undergoing IVF treatment at the fertility clinic who completed all necessary laboratory examinations. In this study, a sample of 67 patients were consisted with 30 women in follitropin alpha and 37 women in follitropin delta who met the inclusion criteria and exclusion criteria. Patient demographics, treatment parameters, hormonal levels, pregnancy outcomes, oocyte retrieval and embryo transfer were studied. Most of the embryo transfers were fresh with mostly good quality. Overall, follitropin delta provides superior outcomes in terms of higher oocyte retrieval rates, better pregnancy rates and more effective ovarian stimulation compared to some other FSH preparations. These advantages make it a valuable option for optimizing fertility treatments, though individual patient factors and treatment protocols should always be considered. [ABSTRACT FROM AUTHOR]