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Simple Summary: Oestrogen and progesterone are two sex hormones that are important in the development of cancer of the inner lining of the uterus and endometrial cancer (EC). Oestrogen binds to the oestrogen receptor (ER) and progesterone to the progesterone receptor (PR). The presence of these receptors is important because the response to hormonal therapy is higher when the receptors are present. However, as EC grows and spreads throughout the body, ER and PR may be lost. In this study, we found that tumours that have spread to other organs throughout the blood and tumours that have spread in the abdomen have a relatively high presence of ER/PR, while tumours located in the lymph nodes have a lower presence of PR. ER/PR-IHC were not lower in tumours that had previously been treated with radiotherapy. This might influence the application of hormonal therapy in the future. Background: Response to hormonal therapy in advanced and recurrent endometrial cancer (EC) can be predicted by oestrogen and progesterone receptor immunohistochemical (ER/PR-IHC) expression, with response rates of 60% in PR-IHC > 50% cases. ER/PR-IHC can vary by tumour location and is frequently lost with tumour progression. Therefore, we explored the relationship between ER/PR-IHC expression and tumour location in EC. Methods: Pre-treatment tumour biopsies from 6 different sites of 80 cases treated with hormonal therapy were analysed for ER/PR-IHC expression and classified into categories 0–10%, 10–50%, and >50%. The ER pathway activity score (ERPAS) was determined based on mRNA levels of ER-related target genes, reflecting the actual activity of the ER receptor. Results: There was a trend towards lower PR-IHC (33% had PR > 50%) and ERPAS (27% had ERPAS > 15) in lymphogenic metastases compared to other locations (p = 0.074). Hematogenous and intra-abdominal metastases appeared to have high ER/PR-IHC and ERPAS (85% and 89% ER-IHC > 50%; 64% and 78% PR-IHC > 50%; 60% and 71% ERPAS > 15, not significant). Tumour grade and previous radiotherapy did not affect ER/PR-IHC or ERPAS. Conclusions: A trend towards lower PR-IHC and ERPAS was observed in lymphogenic sites. Verification in larger cohorts is needed to confirm these findings, which may have implications for the use of hormonal therapy in the future. [ABSTRACT FROM AUTHOR]

Endometriosis, a chronic condition characterized by the growth of endometrial-like tissue outside of the uterus, poses substantial challenges in terms of diagnosis and treatment. Artificial intelligence (AI) has emerged as a promising tool in the field of medicine, offering opportunities to address the complexities of endometriosis. This review explores the current landscape of endometriosis diagnosis and treatment, highlighting the potential of AI to alleviate some of the associated burdens and underscoring common pitfalls and challenges when employing AI algorithms in this context. Women's health research in endometriosis has suffered from underfunding, leading to limitations in diagnosis, classification, and treatment approaches. The heterogeneity of symptoms in patients with endometriosis has further complicated efforts to address this condition. New, powerful methods of analysis have the potential to uncover previously unidentified patterns in data relating to endometriosis. AI, a collection of algorithms replicating human decision-making in data analysis, has been increasingly adopted in medical research, including endometriosis studies. While AI offers the ability to identify novel patterns in data and analyze large datasets, its effectiveness hinges on data quality and quantity and the expertise of those implementing the algorithms. Current applications of AI in endometriosis range from diagnostic tools for ultrasound imaging to predicting treatment success. These applications show promise in reducing diagnostic delays, healthcare costs, and providing patients with more treatment options, improving their quality of life. AI holds significant potential in advancing the diagnosis and treatment of endometriosis, but it must be applied carefully and transparently to avoid pitfalls and ensure reproducibility. This review calls for increased scrutiny and accountability in AI research. Addressing these challenges can lead to more effective AI-driven solutions for endometriosis and other complex medical conditions. [ABSTRACT FROM AUTHOR]

In the context of the global rise of antibiotic resistance, optimising the prevention of infectious complications of caesarean section (CS) with a reassessment of the guidelines for ultra-short antibiotic (AB) regimens is becoming increasingly important. Given the current data on the negative consequences of the use of AB in pregnant women for the fetal microbiota, the role of antiseptics that are used locally, do not pass to the child, and are less likely to cause resistance, have a wider range of antimicrobial activity is increasing. The objective: to provide clinical evidence for the prevention of infectious complications of CS by topical application of an antiseptic with decamethoxin. Materials and methods. A comparative study of two homogeneous groups of women with low infectious risk delivered by elective CS was conducted. In the 1st group (55 women) an antiseptic with decamethoxin was used at all stages of abdominal delivery: preoperative treatment of the skin and vagina, intraoperative irrigation of the inner surface of the uterus, uterine sutures, and subcutaneous tissue. The 2nd group (55 patients) received conventional antibacterial prophylaxis. In the course of clinical and microbiological parallels, ultrasound monitoring of uterine involution, the results of the examination on the 42nd day after CS and information on the condition of the newborn child were used. Results. The absence of infectious complications of puerperium, infection of the surgical site, trends and signs of inflammatory reactions in both groups was revealed. In the 2nd group 5.5% of patients had partial skin suture separation due to seroma formation and transient infiltration of the subcutaneous tissue. The absence of such phenomena in the 1st group should be considered a consequence of the cytoprotective effect of decametoxin. The use of an antiseptic with decametoxin has pharmacoeconomic advantages over antibiotic prophylaxis regimens. Conclusions. The use of antiseptic with decametoxin in the perioperative care of caesarean section combines the possibility of safe reduction of antibiotics, effective antiinfective protection with guaranteed safety for the child. [ABSTRACT FROM AUTHOR]

Ectopic pregnancy is the leading cause of I trimester maternal morbidity and mortality worldwide. Ectopic pregnancy is diagnosed in 1.5–2% of the general population and in 1.4–5.4% of patients after assisted reproductive technologies. In up to 98% of cases, an ectopic pregnancy develops in the fallopian tubes. Signs and symptoms of a ruptured fallopian tube in an ectopic pregnancy can occur between the 6th and 8th weeks of gestation. Interstitial ectopic pregnancy is a type of non-tubal ectopic pregnancy, when the attachment of a fertilized egg occurs at the junction of the interstitial part of the fallopian tube with the uterine myometrium. Localization of ectopic pregnancy not in the fallopian tube is detected infrequently – in 7-10% of all ectopic pregnancies, but this type of pregnancy is associated with a greater number of complications due to late manifestation and diagnostic difficulties. The interstitial part of the fallopian tube is approximately 1–2 cm long and 0.7 mm wide. The gestational sac, implanted in the interstitial part of the fallopian tube, is surrounded by a layer of myometrium, that is, the middle layer of the uterine wall, consisting mainly of smooth muscle cells, as well as supporting interstitial and vascular tissue. The surrounding tissue of the myometrium allows pregnancy to progress up to 12 weeks, and in the presence of its changes at this time, the uterus actually ruptures, which leads to significant bleeding or even death. The article describes a clinical case of an ectopic pregnancy in a 30-year-old woman who was hospitalized at the Perinatal Center of Kyiv after a routine examination for in vitro fertilization. The patient did not have any complaints. During a transvaginal ultrasound examination a progressive interstitial ectopic pregnancy was diagnosed, and the level of β-human chorionic gonadotropin in the blood serum corresponded to 5–6 weeks of gestation. The patient was hospitalized for surgical intervention, as a result of which the ectopic interstitial pregnancy was interrupted by excision of the uterine angle without penetration into its cavity, which was accompanied by minimal blood loss. [ABSTRACT FROM AUTHOR]

Objective This study aimed to compare the effectiveness of sustained uterine compression versus uterine massage in reducing blood loos after a vaginal delivery. Study Design This was a prospective randomized trial conducted at the American University of Beirut Medical Center (AUBMC) between October 2015 and October 2017. Inclusion criteria were women with a singleton pregnancy at ≥36 weeks of gestation, with less than three previous deliveries, who were candidates for vaginal delivery. Participants were randomized into two groups, a sustained uterine compression group (group 1) and a uterine massage group (group 2). Incidence of postpartum hemorrhage (blood loss of ≥500 mL) was the primary outcome. We assumed that the incidence of postpartum hemorrhage at our institution is similar to previously published studies. A total of 545 women were required in each arm to detect a reduction from 9.6 to 4.8% in the primary outcome (50% reduction) with a one-sided α of 0.05 and a power of 80%. Factoring in a 10% dropout rate. Secondary outcomes were admission to intensive care unit (ICU), postpartum complications, drop in hemoglobin, duration of hospital stay, maternal pain, use of uterotonics, or of surgical procedure for postpartum hemorrhage. Results A total of 550 pregnant women were recruited, 273 in group 1 and 277 in group 2. There was no statistically significant difference in baseline characteristics between the two groups. Type of anesthesia, rate of episiotomy, lacerations, and mean birth weight were also equal between the groups. Incidence of the primary outcome was not different between the two groups (group 1: 15.5%, group 2: 15.4%; p = 0.98). There was no statistically significant difference in any of the secondary outcomes between the two groups, including drop in hemoglobin (p = 0.79). Conclusion There was no difference in blood loss between sustained uterine compression and uterine massage after vaginal delivery. Key Points Transabdominal uterine compression and uterine massage are appropriate to prevent postpartum hemorrhage. No significant difference in blood loss or maternal discomfort observed between the two techniques. Both methods are equally effective and either one can be used based on provider preference. [ABSTRACT FROM AUTHOR]

Postpartum hemorrhage (PPH) is a major cause of maternal mortality and disability. A need for simple, inexpensive techniques to prevent PPH and provide treatment exists, particularly in cases where uterotonics cannot be accessed. Uterine massage is recommended as part of the routine active management of the third stage of labor. This study was conducted to determine the effectiveness of uterine massage after delivery of the placenta in reducing postpartum blood loss. Thus, a randomized controlled trial was conducted in Turkey between March 2018 and September 2018. A total of 176 pregnant women (88 in the control and 88 in the uterine massage groups) were randomly allocated to the two groups: one group receiving sustained uterine massage, while the other comprising the control group. The uterine massage group was administered transabdominal uterine massage, starting immediately after delivery of the placenta and continuing every 15 min for a duration of 2 h until the uterus hardened. The blood loss within 2 h of delivery was recorded. Level of significance was taken as p < 0.05, and the chi-square, t, and Mann–Whitney U tests as well as Spearman's correlation and linear regression were employed in the analysis of the data. The average amount blood loss within 2 h of the delivery was significantly higher in the control group than in the massage group (X = 170.49 ± 61.46 and X = 186.20 ± 47.59, p < 0.05). A statistically significant difference was present between the uterine massage and control groups in terms of hemoglobin, hematocrit, WBC, and RCB pre-delivery and pre-discharge (first 24 h) values and in the use of additional uterotonics and the amount of blood loss (p < 0.05). The results of the analysis show that postpartum uterine massage has a reducing effect on the amount of PPH. [ABSTRACT FROM AUTHOR]

Introduction: The puerperium is a time of great change which spans a period of transition from the pinnacle experience of birth to the assumption of the joys. About 14 million women each year affected due to postpartum haemorrhage and results in around 70,000 deaths. Fundal massage is effective way for uterine involution and less risk of postpartum haemorrhage. Aims: The current study is aimed to evaluate the effectiveness of fundal massage on uterine involution among postnatal mothers at selected hospitals and also to find out the association between variables. Methodology Design and Setting: Quantitative approach was adopted. Quasi experimental pretest post-test control group design was used. Non probability consecutive sampling technique were utilized to drawn samples.60 postnatal mothers were screened. Prior to data collection written setting permission obtained from authorities of the various hospitals and inform consent form was obtained from the participants. Investigator has used structured questionnaire for collecting data related to demographic characteristics and clinical variable and modified fundal measurement scale were used to measure the fundal height with the aid of measuring tape. Descriptive and inferential statistics were used to compute the data. Result and conclusion: The present study revealed that mean post-test score in intervention group is 8.53 ±1.66 is less than the mean pretest score 10.93 ± 1.93. Comparison also made between pretest of intervention and control group and calculated 't' value was 1.67, df 58 and which is less than p< 0.05. Whereas in the control group the mean post-test scores 9.56 ± 1.13 and pretest score 11.56 ± 1.13 and calculated 't' value 2.184, df 58 and p >0.05. Out of all demographic variable type of gravid and ambulation after delivery were found significant associated at P value <0.05 level. In this study researcher stated that the fundal massage was effective in improving the uterine involution. This concludes there was significant difference in intervention group compare to control group. [ABSTRACT FROM AUTHOR]

Fibroids of the uterus are a common benign tumor affecting women of childbearing age. Uterine fibroids (UF) can be effectively treated with earlier identification and diagnosis. Its automated diagnosis from medical images is an area where deep learning (DL)-based algorithms have demonstrated promising results. In this research, we evaluated state-of-the-art DL architectures VGG16, ResNet50, InceptionV3, and our proposed innovative dual-path deep convolutional neural network (DPCNN) architecture for UF detection tasks. Using preprocessing methods including scaling, normalization, and data augmentation, an ultrasound image dataset from Kaggle is prepared for use. After the images are used to train and validate the DL models, the model performance is evaluated using different measures. When compared to existing DL models, our suggested DPCNN architecture achieved the highest accuracy of 99.8 percent. Findings show that pre-trained deep-learning model performance for UF diagnosis from medical images may significantly improve with the application of fine-tuning strategies. In particular, the InceptionV3 model achieved 90% accuracy, with the ResNet50 model achieving 89% accuracy. It should be noted that the VGG16 model was found to have a lower accuracy level of 85%. Our findings show that DL-based methods can be effectively utilized to facilitate automated UF detection from medical images. Further research in this area holds great potential and could lead to the creation of cutting-edge computer-aided diagnosis systems. To further advance the state-of-the-art in medical imaging analysis, the DL community is invited to investigate these lines of research. Although our proposed innovative DPCNN architecture performed best, fine-tuned versions of pre-trained models like InceptionV3 and ResNet50 also delivered strong results. This work lays the foundation for future studies and has the potential to enhance the precision and suitability with which UF is detected. [ABSTRACT FROM AUTHOR]

Extraembryonic membranes provide protection, oxygen, water, and nutrients to developing embryos, and their study generates information on the origin of the terrestrial egg and the evolution of viviparity. In this research, the morphology of the extraembryonic membranes and the types of placentation in the viviparous snake Conopsis lineata are described through optical microscopy during early and late gestation. When embryos develop inside the uterus, they become surrounded by a thin eggshell membrane. In early gestation, during stages 16 and 18, the embryo is already surrounded by the amnion and the chorion, and in a small region by the chorioallantois, which is product of the contact between the chorion and the growing allantois. A trilaminar omphalopleure covers the yolk sac from the embryonic hemisphere to the level of the equator where the sinus terminalis is located, and from there a bilaminar omphalopleure extends into the abembryonic hemisphere. Thus, according to the relationship of these membranes with the uterine wall, the chorioplacenta, the choriovitelline placenta, and the chorioallantoic placenta are structured at the embryonic pole, while the omphaloplacenta is formed at the abembryonic pole. During late gestation (stages 35, 36, and 37), the uterus and allantois are highly vascularized. The allantois occupies most of the extraembryonic coelom and at the abembryonic pole, it contacts the omphaloplacenta and form the omphalallantoic placenta. This is the first description of all known placenta types in Squamata for a snake species member of the subfamily Colubrinae; where an eggshell membrane with 2.9 μm in width present throughout development is also evident. The structure of extraembryonic membranes in C. lineata is similar to that of other oviparous and viviparous squamate species. The above indicates not only homology, but also that the functional characteristics have been maintained throughout the evolution of the reproductive type., (© 2024 The Author(s). Journal of Morphology published by Wiley Periodicals LLC.)

Vaginal childbirth is the final phase of pregnancy when one or more fetuses pass through the birth canal from the uterus, and it is a biomechanical process. The uterine active contraction, causing the pushing force on the fetus, plays a vital role in regulating the fetus delivery process. In this project, the active contraction behaviors of muscle tissue were first modeled and investigated. After that, a finite element method (FEM) model to simulate the uterine cyclic active contraction and delivery of a fetus was developed in ls-dyna. The active contraction was driven through contractile fibers modeled as one-dimensional truss elements, with the Hill material model governing their response. Fibers were assembled in the longitudinal, circumferential, and normal (transverse) directions to correspond to tissue microstructure, and they were divided into seven regions to represent the strong anisotropy of the fiber distribution and activity within the uterus. The passive portion of the uterine tissue was modeled with a Neo Hookean hyperelastic material model. Three active contraction cycles were modeled. The cyclic uterine active contraction behaviors were analyzed. Finally, the fetus delivery through the uterus was simulated. The model of the uterine active contraction presented in this paper modeled the contractile fibers in three-dimensions, considered the anisotropy of the fiber distribution, provided the uterine cyclic active contraction and propagation of the contraction waves, performed a large deformation, and caused the pushing effect on the fetus. This model will be combined with a model of pelvic structures so that a complete system simulating the second stage of the delivery process of a fetus can be established., (Copyright © 2024 by ASME; reuse license CC-BY 4.0.)

In cattle, the endometrium during diestrus and early pregnancy displays cellular responses that are consequences of prior, transient stimuli. Goal was to establish a model to study cellular memory in the endometrium. The hypothesis is that stimuli given to endometrium in vivo are retained as a cellular memory that remains after bovine uterine epithelial cells (BUECs) are isolated, cultured, and further stimulated in vitro. Objectives were to measure BUEC proliferation/migration and responsiveness to recombinant bovine Interferon-tau (rbIFNT) in vitro: among cows that showed estrus (experiment 1 [Exp1]), cows that became or not pregnant to artificial insemination (Exp2), cows that received or not supplemental progesterone (P4; Exp3) and cows that received or not a COX-1/2 inhibitor (Exp4). Only cows that displayed estrus were included in studies. For all experiments endometrial cytology was collected 4 days after estrus, BUECs were cultured, propagated, and submitted to rbIFNT treatment and an in vitro scratch assay. In Exp1, different cows spontaneously grouped according to proliferative/migratory capacity and responsiveness to rbIFNT of their respective BUECs. In Exp2, BUECs from pregnant cows showed greater rbIFNT responsiveness and cellular proliferation. In Exp3, BUECs from cows supplemented with P4 presented inhibited proliferation and increased expression of RSAD2. In Exp4, Flunixin Meglumine modified rbIFNT responsiveness of BUECs in an IFN-signaling pathway-specific manner. In conclusion, physiological and pharmacological stimuli received by the endometrium in vivo were retained as cellular memory in BUECs, persisted in culture, and changed BUEC proliferation/migration and responsiveness to rbIFNT, which are characteristics associated with fertility in cattle., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The current trends in the development of methods for non-invasive prediction of premature birth based on the electromyogram of the uterus, i.e., electrohysterogram (EHG), suggest an ever-increasing use of large number of features, complex models, and deep learning approaches. These "black-box" approaches rarely provide insights into the underlying physiological mechanisms and are not easily explainable, which may prevent their use in clinical practice. Alternatively, simple methods using meaningful features, preferably using a single feature (biomarker), are highly desirable for assessing the danger of premature birth. To identify suitable biomarker candidates, we performed feature selection using the stabilized sequential-forward feature-selection method employing learning and validation sets, and using multiple standard classifiers and multiple sets of the most widely used features derived from EHG signals. The most promising single feature to classify between premature EHG records and EHG records of all other term delivery modes evaluated on the test sets appears to be Peak Amplitude of the normalized power spectrum (PA) of the EHG signal in the low frequency band (0.125-0.575 Hz) which closely matches the known Fast Wave Low (FWL) frequency band. For classification of EHG records of the publicly available TPEHG DB, TPEHGT DS, and ICEHG DS databases, using the Partition-Synthesis evaluation technique, the proposed single feature, PA, achieved Classification Accuracy (CA) of 76.5% (AUC of 0.81). In combination with the second most promising feature, Median Frequency (MF) of the power spectrum in the frequency band above 1.0 Hz, which relates to the maternal resting heart rate, CA increased to 78.0% (AUC of 0.86). The developed method in this study for the prediction of premature birth outperforms single-feature and many multi-feature methods based on the EHG, and existing non-invasive chemical and molecular biomarkers. The developed method is fully automatic, simple, and the two proposed features are explainable., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Pirnar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Large vesicle extrusion from neurons may contribute to spreading pathogenic protein aggregates and promoting inflammatory responses, two mechanisms leading to neurodegenerative disease. Factors that regulate the extrusion of large vesicles, such as exophers produced by proteostressed C. elegans touch neurons, are poorly understood. Here, we document that mechanical force can significantly potentiate exopher extrusion from proteostressed neurons. Exopher production from the C. elegans ALMR neuron peaks at adult day 2 or 3, coinciding with the C. elegans reproductive peak. Genetic disruption of C. elegans germline, sperm, oocytes, or egg/early embryo production can strongly suppress exopher extrusion from the ALMR neurons during the peak period. Conversely, restoring egg production at the late reproductive phase through mating with males or inducing egg retention via genetic interventions that block egg-laying can strongly increase ALMR exopher production. Overall, genetic interventions that promote ALMR exopher production are associated with expanded uterus lengths and genetic interventions that suppress ALMR exopher production are associated with shorter uterus lengths. In addition to the impact of fertilized eggs, ALMR exopher production can be enhanced by filling the uterus with oocytes, dead eggs, or even fluid, supporting that distention consequences, rather than the presence of fertilized eggs, constitute the exopher-inducing stimulus. We conclude that the mechanical force of uterine occupation potentiates exopher extrusion from proximal proteostressed maternal neurons. Our observations draw attention to the potential importance of mechanical signaling in extracellular vesicle production and in aggregate spreading mechanisms, making a case for enhanced attention to mechanobiology in neurodegenerative disease., Competing Interests: GW, RG, SS, EC, AM, AS, DJ, SS, EF, IM, KN, DH, BG, MD No competing interests declared, (© 2024, Wang, Guasp, Salam et al.)

Neotropical freshwater stingrays of the subfamily Potamotrygoninae exhibit aplacental viviparity with uterine trophonemata. In this reproductive mode, females nourish and provide oxygenation to the embryo via the mucosa of the uterine wall. The aim of this study was to describe and histologically quantify the tissue components of the gravid uterus in an Amazonian freshwater stingray. Adult females of Potamotrygon wallacei were studied in different reproductive periods: resting stage, pregnant, and postpartum. During reproductive rest, the left ovary has numerous follicles compared to the right side. Therefore, uterine fertility is usually higher on the left side. The presence of an embryo in the right uterus suggests that the right ovary is also functional, although this only occurs in larger females. In females at reproductive rest, the wall of the uterus is formed by a mucosal layer (without the trophonemata) that contributes 16.7% to the thickness, while the myometrium accounts for 83.3% of the thickness. The mass-specific volume of the mucosal layer, inner circular, and outer longitudinal smooth muscle sheets tend to increase in the gravid uterus, indicating hypertrophy and hyperplasia of these components. During pregnancy, the trophonemata undergo marked tissue remodeling. Epithelial cells are organized into glandular acini and have apical secretory vesicles; furthermore, peripheral blood vessels proliferate and become dilated. These characteristics demonstrate that the gravid uterus of P. wallacei presents intense uterolactation activity and provides oxygenation to the fetus. Tissue remodeling occurs only in the uterus with the presence of an embryo. During postpartum, females have low body condition factor indicating a high reproductive cost. This study contributes to the knowledge of the reproductive biology of this species and will help us understand the impacts of climate change on the breeding areas of potamotrygonids., (© 2024 Wiley Periodicals LLC.)

Premature birth poses a challenge to public health, with one in ten babies being born prematurely worldwide. The pathological distension of the uterus can create tension in the uterine wall, triggering contractions that may lead to birth, including premature birth. While there has been an increase in the use of computational models to study pregnancy in recent years, ethical challenges have limited research on the mechanical properties of the uterus during gestation. This study proposes a biomechanical model based on a stretch-driven growth mechanism to describe uterine evolution during the second half of the gestational period. The constitutive model employed is anisotropic, reflecting the presence of fibers in uterine tissue, and it is also considered incompressible. The geometric model representing the uterine body was derived from truncated ellipsoids, subject to intrauterine pressure as loading. Simulation results indicate that the proposed model is effective in reproducing growth patterns documented in the literature, such as simultaneous increases in intrauterine volume and uterine tissue volume, accompanied by a reduction in uterine wall thickness within limits reported in experimental data., Competing Interests: Declaration of competing interest The authors certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Uterocervical motions and organ filling during cervical cancer conformal radiotherapy is complex. This prospective, observational study investigated set-up margins (clinical target vo, ume [CTV] to planning target volume [PTV]) for pelvic nodal CTV and internal margin (CTV to internal target volume [ITV]) expansions for uterocervical movements during cervical cancer radiotherapy. During cervical cancer radiotherapy, a daily kilovoltage, cone-beam computed tomography (CBCT) scan was acquired. Bony anatomy-based rigid co-registration and matching to vessels/pelvic nodal region was carried out to document shifts, errors (systematic and random) and to calculate CTV to PTV margins. Subsequently, soft-tissue matching was carried out at the mid-cervical region and uterine fundus to record shifts, errors and to calculate CTV to ITV margins. In 67 patients, 1380 CBCT scans were analysed. The mean (±standard deviation) couch shifts for CTV pelvic nodal region in all directions were within 4.5–5.3 mm, systematic and random errors 3.0–3.6 mm and set-up margins of within 10 mm (except anterior margin 10.3 mm). For the mid-cervical region, mean shifts were 4.5–5.5 mm, systematic and random errors 2–4 mm amounting to <10 mm internal margins (CTV–ITV for cervix) and for uterine fundus mean (±standard deviation) shifts were larger in the superior direction (12.1 mm) but 4.0–7.5 mm in other directions, systematic and random errors 2–7 mm amounting to anisotropic margins in various directions (10 mm in anterior–posterior and lateral directions, 12–20 mm in superior–inferior directions) (CTV–ITV for uterine fundus). Our study suggests anisotropic CTV to ITV and CTV to PTV margins for cervical cancer radiotherapy. • Investigation of uterocervical motions and set-up margins required for primary and nodal CTV during cervical cancer radiotherapy. • Detailed analysis including uterocervical sub-volumes, factors affecting the internal organ motions tumour regression and impact on CTV. • Based on the various shifts, we report internal margins (CTV to ITV) and set-up margins (CTV to PTV) for cervical cancer radiotherapy. • Results suggest an anisotropic internal margin (CTV to ITV) and set-up margins (CTV to PTV) within a defined organ filling protocol environment. [ABSTRACT FROM AUTHOR]

To examine the uterine cavity and/or to perform hysteroscopic surgery, one has to access the uterine cavity through the cervix, distend the cavity with a fluid (liquid or gas) to visualize it with a telescope and/or a camera system and use energy (mechanical or thermal) to affect and/or remove tissue. Distension of the uterine cavity then is an important component of hysteroscopy, and during the last century, numerous attempts have been made to achieve an undistorted and unobstructed panoramic view of the uterine cavity. In order to achieve this goal, the uterine cavity has been distended with fluids using a variety of techniques, including gravity-assisted systems, pressure cuffed systems, and electronic pumps. Excessive fluid intravasation during hysteroscopy can lead to significant complications, and hence, automated fluid delivery systems have been developed recently to provide a safe and more efficient method of fluid delivery. This review aims to describe the evolution of distension media delivery systems chronologically from the 1900s to the present day. [ABSTRACT FROM AUTHOR]

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Effective interplay between the uterus and the embryo is essential for pregnancy establishment; however, convenient methods to screen embryo implantation success and maternal uterine response in experimental mouse models are currently lacking. Here, we report 3DMOUSEneST, a groundbreaking method for analyzing mouse implantation sites based on label-free higher harmonic generation microscopy, providing unprecedented insights into the embryo-uterine dynamics during early pregnancy. The 3DMOUSEneST method incorporates second-harmonic generation microscopy to image the three-dimensional structure formed by decidual fibrillar collagen, named 'decidual nest', and third-harmonic generation microscopy to evaluate early conceptus (defined as the embryo and extra-embryonic tissues) growth. We demonstrate that decidual nest volume is a measurable indicator of decidualization efficacy and correlates with the probability of early pregnancy progression based on a logistic regression analysis using Smad1/5 and Smad2/3 conditional knockout mice with known implantation defects. 3DMOUSEneST has great potential to become a principal method for studying decidual fibrillar collagen and characterizing mouse models associated with early embryonic lethality and fertility issues., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Determining the female animal cycle is crucial in preclinical studies and animal husbandry. Changes in hormone levels during the cycle affect physiological responses, including altered contractility of the visceral smooth muscle. The study aimed to identify estrus and anestrus using smooth muscle electromyographic (SMEMG) measurements, in vivo fluorescent imaging (IVIS) and in vitro organ contractility of the uterus and cecum. The study involved sexually mature female Sprague-Dawley rats, aged 10-12 weeks. The rats received a daily injection of cetrorelix acetate solution for 7 days, while another group served as the control. The animals were subjected to gastrointestinal and myometrial SMEMG. The change in αvβ3 integrin activity was measured with IVIS in the abdominal cavity. Contractility studies were performed in isolated organ baths using dissected uterus and cecum samples. Plasma samples were collected for hormone level measurements. A 3-fold increase in spontaneous contraction activity was detected in SMEMG measurements, while a significant decrease in αvβ3 integrin was measured in the IVIS imaging procedure. Cetrorelix reduced the level of LH and the progesterone / estradiol ratio, increased the spontaneous activity of the cecum rings, and enhanced KCl-evoked contractions in the uterus. We found a significant change in the rate of SMEMG signals, indicating simultaneous increases in the contraction of the cecum and the non-pregnant uterus, as evidenced by isolated organ bath results. Fluorescence imaging showed high levels of uterine αvβ3 integrin during the proestrus-estrus phase, but inhibiting the sexual cycle reduced fluorescence activity. Based on the results, the SMEMG and IVIS imaging methods are suitable for detecting estrus phase alterations in rats., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Szucs et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Mammalian reproduction is more inefficient than expected and embryo/conceptus implantation into the maternal endometrium is considered to be a rate-limiting process. Although extensive physiological and structural diversity exists among mammalian species, the basic molecular mechanisms underlying successful implantation are conserved. The extensive use of genetically engineered mouse models has provided considerable information on uterine receptivity for embryo implantation. The molecular mechanisms and cellular processes identified thus far require further validation in other mammalian species. In this review, representative ovarian steroid hormone-induced signaling pathways controlling uterine adaptation are presented based on the results of rodent studies. Selected examples of functional conservation in mammals, such as humans and cattle, are briefly described. To date, molecular therapeutic trials for fertility improvement have not been conducted. Considerable efforts are required to provide further understanding of these molecular mechanisms. Such understanding will contribute to the development of reliable clinical diagnostics and therapeutics for implantation failure, leading to reproductive success in a wide variety of mammals in the future.

The aims of this study were to determine the effect of the embryo flushing technique and the number of flushing attempts performed by operators of different experience on embryo recovery (ER). Ten non-lactating mares were inseminated with the same stallion in six cycles each (n = 60). Embryo flushing (EF) was performed 7-9 days after ovulation by three operators (OP; 20 EF cycles each): OP1 had performed >500 EF before the study, while OP2 and 3 had performed 0 EF. Each EF was performed with 2 flushing attempts (FA) using 1L of ringer's lactate "in-and-out" using two EF techniques: 1) uterine massage (UM): continuous ballottement and massage of the uterus per rectum during ringer lactate recovery, 2) gravity flow (GF): the ringer lactate was allowed to flow back without massaging the uterus. In both groups, 20 IU of oxytocin were administered at the second FA and the ringer lactate was allowed to remain in the uterus for 3 min before recovery. An extra FA was performed in each group using 0.5 L of ringer lactate and uterine massage. More embryos (P < 0.05) per ovulation were recovered in the UM (17/33, 0.51) than in the GF group (8/36, 0.22). For the UM group, 16/17 embryos (94.1 %) were recovered in the first FA, while only one embryo in the second FA (1/17, 5.9 %). In the GF group, 4 embryos were recovered in each FA. No embryo was found in the extra FA in the UM group, while seven additional embryos were found in the GF group (5/7 flushed by OP1; P < 0.05). The overall ER per cycle was 70, 40, and 45 % for OP1, 2 and 3, respectively. In conclusion, highest embryo recovery is achieved in EF performed with UM, with the majority of embryos being flushed in the first FA., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Study Question: Can a co-culture of three cell types mimic the in vivo layers of the uterine wall?, Summary Answer: Three protocols tested for co-culture of endometrial epithelial cells (EEC), endometrial stromal cells (ESC), and myometrial smooth muscle cells (MSMC) led to formation of the distinct layers that are characteristic of the structure of the uterine wall in vivo., What Is Known Already: We previously showed that a layer-by-layer co-culture of EEC and MSMC responded to peristaltic wall shear stresses (WSS) by increasing the polymerization of F-actin in both layers. Other studies showed that WSS induced significant cellular alterations in epithelial and endothelial cells., Study Design, Size, Duration: Human EEC and ESC cell lines and primary MSMC were co-cultured on a collagen-coated synthetic membrane in custom-designed wells. The co-culture model, created by seeding a mixture of all cells at once, was exposed to steady WSS of 0.5 dyne/cm2 for 10 and 30 min., Participants/materials, Setting, Methods: The co-culture of the three different cells was seeded either layer-by-layer or as a mixture of all cells at once. Validation of the models was by specific immunofluorescence staining and confocal microscopy. Alterations of the cytoskeletal F-actin in response to WSS were analyzed from the 2-dimensional confocal images through the Z-stacks following a previously published algorithm., Main Results and the Role of Chance: We generated three multi-cell in vitro models of the uterine wall with distinct layers of EEC, ESC, and MSMC that mimic the in vivo morphology. Exposure of the mixed seeding model to WSS induced increased polymerization of F-actin in all the three layers relative to the unexposed controls. Moreover, the increased polymerization of F-actin was higher (P-value < 0.05) when the length of exposure was increased from 10 to 30 min. Furthermore, the inner layers of ESC and MSMC, which are not in direct contact with the applied shearing fluid, also increased their F-actin polymerization., Large Scale Data: N/A., Limitations, Resons for Caution: The mixed seeding co-culture model was exposed to steady WSS of one magnitude, whereas the uterus is a dynamic organ with intra-uterine peristaltic fluid motions that vary in vivo with different time-dependent magnitude. Further in vitro studies may explore the response to peristaltic WSS or other physical and/or hormonal perturbations that may mimic the spectrum of pathophysiological aspects., Wider Implications of the Findings: Numerous in vitro models were developed in order to mimic the human endometrium and endometrium-myometrium interface (EMI) region. The present co-culture models seem to be the first constructed from EEC, ESC, and MSMC on a collagen-coated synthetic membrane. These multi-cell in vitro models better represent the complex in vivo anatomy of the EMI region. The mixed seeding multi-cell in vitro model may easily be implemented in controlled studies of uterine function in reproduction and the pathogenesis of diseases., Study Finding/competing Interest(s): This study was supported in part by Tel Aviv University funds. All authors declare no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The fertilization rate is an important index to evaluate the reproductive capacity of hens, which is mainly affected by semen quality, timing of artificial insemination (AI), and the ability to store sperm. A high sperm storage (SS) capacity can extend the interval, reduce the frequency, and decrease the labor costs of AI. However, relatively few studies have investigated the SS capacity of hens. Therefore, the aims of the present study were to identify factors influencing the SS capacity of Guangxi partridge chickens and to explore the impact of the sperm count in different sections of the oviduct and sperm storage tubules (SSTs), in addition to the number and surface area of SSTs on SS capacity at different time points after AI. We found that SS capacity was positively correlated to the egg production rate (P < 0.01) and body length (P < 0.05). On post-AI days 5, 10, and 15, the sperm count was higher in uterus-vagina junction (UVJ) than the magnum, isthmus, and infundibulum (P < 0.01), but gradually decreased over time. Also, the duration of SS and the sperm count of the UVJ was greater in the high SS group than the low SS group (P < 0.05). Histopathological analysis of the UVJ showed that the number and surface area of the SSTs (P < 0.01), as well as the proportion of SSTs containing sperm, were greater in the high SS group at all time points post AI (P < 0.01), while the proportion of SSTs containing sperm gradually decreased over time. Collectively, these results highlight the potential for selective breeding of SS capacity and show that SS capacity is related to laying performance and body length of Guangxi partridge hens. In addition, SS capacity was positively correlated to the surface area of SSTs and the proportion containing sperm. A greater sperm count stored in the UVJ was correlated to more sperm transported to the infundibulum and subsequent greater SS capacity of hens., Competing Interests: DISCLOSURES The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Uterine contractions in the myometrium occur at multiple scales, spanning both organ and cellular levels. This complex biological process plays an essential role in the fetus delivery during the second stage of labor. Several finite element models of active uterine contractions have already been developed to simulate the descent of the fetus through the birth canal. However, the developed models suffer severe reliability issues due to the uncertain parameters. In this context, the present study aimed to perform the uncertainty quantification (UQ) of the active uterine contraction simulation to advance our understanding of pregnancy mechanisms with more reliable indicators. A uterus model with and without fetus was developed integrating a transversely isotropic Mooney-Rivlin material with two distinct fiber orientation architectures. Different contraction patterns with complex boundary conditions were designed and applied. A global sensitivity study was performed to select the most valuable parameters for the uncertainty quantification (UQ) process using a copula-based Monte Carlo method. As results, four critical material parameters ( C 1 , C 2 , K , Ca 0 ) of the active uterine contraction model were identified and used for the UQ process. The stress distribution on the uterus during the fetus descent, considering first and second fiber orientation families, ranged from 0.144 to 1.234 MPa and 0.044 to 1.619 MPa, respectively. The simulation outcomes revealed also the segment-specific contraction pattern of the uterus tissue. The present study quantified, for the first time, the effect of uncertain parameters of the complex constitutive model of the active uterine contraction on the fetus descent process. As perspectives, a full maternal pelvis model will be coupled with reinforcement learning to automatically identify the delivery mechanism behind the cardinal movements of the fetus during the active expulsion process., (© 2024. International Federation for Medical and Biological Engineering.)

Artificial insemination (AI) plays a critical role in facilitating rapid genetic and production gains within the sheep industry. However, variable rates of AI success remain a concern for the industry and a barrier to adoption. Furthermore, the degree to which female factors influence the success of intrauterine laparoscopic AI rather than natural mating remains unknown. As such, this study investigates the effect of several factors collected during the time of AI, on the success of intrauterine laparoscopic AI. Data was generously donated by artificial breeding companies and stud breeders during routine commercial AI operations. AI data was collected over 3 breeding seasons during commercial AI programs (N = 24 programs) using Merino ewes (N = 24,700). Sire ID (N = 253), time of AI following progesterone removal (approx. 43-59 h post removal), uterine tone and intra-abdominal fat (both scored 1-5) as well as age of the ewe were all recorded at the time of AI. Transcutaneous ultrasound subsequently determined pregnancy rate approximately 55 days post-AI. A multivariate regression analysis was performed and revealed pregnancy success to increase when semen was inseminated into a ewe with a uterine tone score of 4 or 5 (P < 0.001). The remaining factors fell short of significance within the multivariate model. An interclass coefficient variation matrix was also used to determine the proportion of variation contributed to AI success by random factors allocated in the model; site, sire, AI date and breeding season (45.99 %, 29.94 %, 15.15 % and 8.92 %, respectively). These results highlight the influence of uterine tone on ewe fertility following laparoscopic AI, but also that program location and the sire used can further modify this influence on pregnancy rate. These factors must now be considered in combination with semen factors per individual sire used during AI to ascertain the contribution of several factors to the success of laparoscopic AI in Australia., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Parturition is a complex physiological process that must occur in a reliable manner and at an appropriate gestation stage to ensure a healthy newborn and mother. To this end, hormones that affect the function of the gravid uterus, especially progesterone (P4), 17β-estradiol (E 2 ), oxytocin (OT), and prostaglandins (PGs), play pivotal roles. P4 via the nuclear P4 receptor (PR) promotes uterine quiescence and for most of pregnancy exerts a dominant block to labor. Loss of the P4 block to parturition in association with a gain in prolabor actions of E 2 are key transitions in the hormonal cascade leading to parturition. P4 withdrawal can occur through various mechanisms depending on species and physiological context. Parturition in most species involves inflammation within the uterine tissues and especially at the maternal-fetal interface. Local PGs and other inflammatory mediators may initiate parturition by inducing P4 withdrawal. Withdrawal of the P4 block is coordinated with increased E 2 actions to enhance uterotonic signals mediated by OT and PGs to promote uterine contractions, cervix softening, and membrane rupture, i.e., labor. This review examines recent advances in research to understand the hormonal control of parturition, with focus on the roles of P4, E 2 , PGs, OT, inflammatory cytokines, and placental peptide hormones together with evolutionary biology of and implications for clinical management of human parturition.

Uterine muscle contractility is essential for reproductive processes including sperm and embryo transport, and during the uterine cycle to remove menstrual effluent. Even still, uterine contractions have primarily been studied in the context of preterm labor. This is partly due to a lack of methods for studying the uterine muscle contractility in the intact organ. Here, we describe an imaging-based method to evaluate mouse uterine contractility of both the longitudinal and circular muscles in the cycling stages and in early pregnancy. By transforming the image-based data into three-dimensional spatiotemporal contractility maps, we calculate waveform characteristics of muscle contractions, including amplitude, frequency, wavelength, and velocity. We report that the native organ is highly contractile during the progesterone-dominant diestrus stage of the cycle when compared to the estrogen-dominant proestrus and estrus stages. We also observed that during the first phase of uterine embryo movement when clustered embryos move toward the middle of the uterine horn, contractions are dynamic and non-uniform between different segments of the uterine horn. In the second phase of embryo movement, contractions are more uniform and rhythmic throughout the uterine horn. Finally, in Lpar3-/- uteri, which display faster embryo movement, we observe global and regional increases in contractility. Our method provides a means to understand the wave characteristics of uterine smooth muscle in response to modulators and in genetic mutants. Better understanding uterine contractility in the early pregnancy stages is critical for the advancement of artificial reproductive technologies and a possibility of modulating embryo movement during clinical embryo transfers., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for the Study of Reproduction.)

Pregnancy is intricately regulated by the interactions between various bioactive substances secreted by the conceptus, uterus, and corpus luteum (CL). Interferon-τ, synthesized and secreted by the conceptus, plays a central role in the interaction mechanism of maternal recognition in cows. Chemokines, chemotaxis mediators that are primarily secreted by immune cells, regulate various reproductive responses in various species. Although there are scattered reports on the potential roles of chemokines in the bovine CL and the uterus during the estrous cycle, there is little information on chemokines in these organs during pregnancy. Therefore, in this review, we discuss the possible physiological roles of chemokines in the CL and uterus of pregnant cows, focusing on our recent findings on chemokines and changes in their receptor expression in the CL and endometrium of cows at some stages of pregnancy.

Uterus transplantation is a non-lifesaving vascularized composite allotransplantation procedure requiring immunosuppression until removal of the graft. The focus of uterus transplantation is changing regarding refining individual treatment procedures included in this complex treatment of absolute uterine factor infertility, such as robot-assisted donor hysterectomy. The inferior hypogastric nerve plexus should be preserved during robotic dissection of the ureter and uterine vessels to prevent postoperative complications such as urine and fecal evacuation disturbances and sexual disorders. As most uterus transplantations have been performed in living donor concepts, robot-assisted donor hysterectomy should contribute to increased availability of uterus transplantation, particularly because it uses the precise blood-less technique of surgical dissection in the deep pelvis and has cosmetic benefits among living donors. [ABSTRACT FROM AUTHOR]

Although dystocia in mares is uncommon, it may be brought on by the way the fetal extremities develop. Dystocia in horses is a serious condition. The referral veterinary polyclinic of ICAR-IVRI received a call about a stray mare who had been straining for the last four hours. She was about 6-7 years old. The absence of foetal responses revealed a dead foetus, and rectal examination indicated that it to be a case of lateral deviation of the head. For the purpose of facilitating head-deviation correction, the foetus was repulsed back into the uterus. A forcible extraction was used to remove the dead foetus following the use of the obstetrical hook to adjust the fetal head position. Anti-inflammatory drugs along with antibiotics were administered. Additionally, tetanus shots were administered prophylactically. The most frequent cause of dystocia in the mare is head deviation, which is a critical condition that can affect both the dam and the foetus. [ABSTRACT FROM AUTHOR]

The pH–CO2–HCO3− system is a ubiquitous biological regulator with important functional implications for reproduction. Knowledge of the physiological values of its components is relevant for reproductive biology and the optimization of Assisted Reproductive Technologies (ARTs). However, in situ measurements of these parameters in the uterus are scarce or null. This study describes a non-invasive method for in situ time-lapse recording of pH and CO2 within the uterus of non-anesthetized sows. Animals were at three different reproductive conditions, estrous with no insemination and two hours after insemination, and diestrous. From pH and CO2 data, HCO3− concentration was estimated. The non-invasive approach to the porcine uterus with novel optical probes allowed the obtaining of in situ physiological values of pH, CO2, and HCO3−. Variable oscillatory patterns of pH, CO2 and HCO3− were found independently of the estrous condition. Insemination did not immediately change the levels of uterine pH, CO2 (%) and HCO3− concentration, but all the values were affected by the estrous cycle decreasing significantly at diestrous condition. This study contributes to a better understanding of the in vivo regulation of the pH-CO2-HCO3− system in the uterus and may help to optimize the protocols of sperm treatment for in vitro fertilization. [ABSTRACT FROM AUTHOR]

This study aimed to systematically determined the effect of 28 h ahemeral light cycle on production performance, egg quality, blood parameters, uterine morphological characteristics, and gene expression of hens during the late laying period. At 74 wk, 260 Hy-Line Brown layers were randomly divided into 2 groups of 130 birds each and in duplicates. Both a regular (16L:8D) and an ahemeral light cycle (16L:12D) were provided to the hens. The oviposition pattern in an ahemeral cycle shifted into darkness, with oviposition mostly occurring 3 to 5 h after light out. Production performance was unaffected by light cycle (P > 0.05). Nonetheless, compared to the normal group, the ahemeral group exhibited increased egg weight, eggshell weight, eggshell percentage, yolk percentage, eggshell thickness, and eggshell strength (P < 0.05). There were rhythmic changes in the uterine morphological structure in both cycles, however, the ahemeral group maintained a longer duration and had more uterine folds than the normal group. In the ahemeral cycle, the phases of the CLOCK and PER2 genes were phase-advanced for 3.96 h and 4.54 h compared to the normal cycle. The PHLPP1 gene, which controls clock resetting, exhibited a substantial oscillated rhythm in the ahemeral group (P < 0.05), while the expression of genes presenting biological rhythm, such as CRY2 and FBXL3, was rhythmically oscillated in normal cycle (P < 0.05). The ITPR2 gene, which regulates intracellular Ca 2+ transport, displayed a significant oscillated rhythm in ahemeral alone (P < 0.05), while the CA2 gene, which presents biomineralization, rhythmically oscillated in both cycles (P < 0.05). The ahemeral cycle caused 2.5 h phase delays in the CA2 gene compared to the normal cycle. In conclusion, the 28 h ahemeral light cycle preserved the high condition of the uterine folds and changed the uterine rhythms of CLOCK, PER2, ITPR2, and CA2 gene expression to improve ion transport and uterine biomineralization., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The developmental origins of health and disease (DOHaD) shows that a relationship exists between parental environment at large, foeto-placental development and the risk for the offspring to develop non-transmittable disease(s) in adulthood. This concept has been validated in both humans and livestock. In mammals, after fertilization and time spent free in the maternal reproductive tract, the embryo develops a placenta that, in close relationship with maternal endometrium, is the organ responsible for exchanges between dam and foetus. Any modification of the maternal environment can lead to adaptive mechanisms affecting placental morphology, blood flow, foetal-maternal exchanges (transporters) and/or endocrine function, ultimately modifying placental efficiency. Among deleterious environments, undernutrition, protein restriction, overnutrition, micronutrient deficiencies and food contaminants can be outlined. When placental adaptive capacities become insufficient, foetal growth and organ formation is no longer optimal, including foetal gonadal formation and maturation, which can affect subsequent offspring fertility. Since epigenetic mechanisms have been shown to be key to foetal programming, epigenetic modifications of the gametes may also occur, leading to inter-generational effects. After briefly describing normal gonadal development in domestic species and inter-species differences, this review highlights the current knowledge on intra-uterine programming of offspring fertility with a focus on domestic animals and underlines the importance to assess transgenerational effects on offspring fertility at a time when new breeding systems are developed to face the current climate changes., (© 2023 The Authors. Reproduction in Domestic Animals published by Wiley‐VCH GmbH.)

Background: Extracellular vesicles (EVs) are membrane-bound vesicles containing various proteins, lipids, and nucleic acids. EVs are found in many body fluids, such as blood and urine. The release of EVs can facilitate intercellular communication through fusion with the plasma membrane or endocytosis into the recipient cell or through internalization of the contents. Recent studies have reported that EVs isolated from human endometrial epithelial cells (EECs) promote sperm fertilization ability. EVs from uterine flushing fluid more closely resemble the physiological condition of the uterus. However, it is unclear whether EVs derived directly from uterine flushing fluid have the same effect on sperm. This study aimed to research the effect of EVs from uterine flushing fluid on sperm., Methods: EVs were isolated from the uterine flushing fluid. The presence of EVs was confirmed by nanoparticle tracking analysis (NTA), Western blot, and transmission electron microscopy (TEM). EVs were incubated with human sperm for 2 h and 4 h. The effects of EVs on sperm were evaluated by analyzing acrosome reaction, sperm motility, and reactive oxygen species (ROS)., Results: The EVs fractions isolated from the uterine fluid were observed in cup-shaped vesicles of different sizes by TEM. All isolated vesicles contained similar numbers of vesicles in the expected size range (30-200 nm) by NTA. CD9 and CD63 were detected in EVs by western blot. Comparing the motility of the two groups incubated sperm motility significantly differed at 4 h. The acrosome reactions were promoted by incubating with EVs significantly. ROS were increased in sperm incubated with EVs., Conclusion: Our results showed EVs present in the uterine fluid. Acrosome reactions and ROS levels increased in human sperm incubated with EVs. EVs from uterine fluid can promote the capacitation of human sperm. The increased capacitation after sperm interaction with EVs suggests a possible physiological effect during the transit of the uterus., Competing Interests: The authors declare there are no competing interests., (©2024 Deng et al.)

The semen of boar is characterized by ejaculation in well-differentiated fractions with specific concentration, composition, and volume. The 'sperm-rich fraction' (SRF), the most concentrated seminal fraction, is habitually collected in insemination centers to make artificial insemination (AI) doses. The absence of the other fractions in AI doses could alter the uterine reaction to AI and not trigger essential responses that could maximize fertility. Thus, there is an urge to ascertain the impact of different ejaculate fractions on the uterus after AI to optimize the semen doses. This work analyzed specific parameters related to fertility in pregnant artificially inseminated sows (n = 15) with ac-cumulative fractions of the semen of boars (n = 6): F1, composed of the sperm-rich fraction (SRF); F2, composed of F1 plus the intermediate fraction; F3, composed of F2 plus the post-SRF. Non-inseminated sows (n = 5) were included as control (C). The different types of seminal dose did not affect the number of ovulated follicles (CL; corpora lutea, p > 0.05) but did affect the embryo development (p < 0.05). The proportion of embryos in morula stages was significantly higher in AI-F1 sows (84.4%, p < 0.05). Morulas and blastocysts were balanced in AI-F2 or AI-F3 (p > 0.05). Independently of the type of seminal dose (F1, F2, or F3), we observed by immunohistochemistry that AI significantly increased uterine vascularization, although with some anatomical differences. The cranial region of the uterine horns was significantly more vascularized in AI-F1 or AI-F2 sows (26.7 ± 2.3 and 28.6 ± 2.0%, respectively), and AI-F3 showed significantly less vascularization at that point (17.8 ± 1.6%, p < 0.05). To summarize, the synergistic effect of all ejaculate fractions accelerates embryo development, at least during the preimplantation period, and increases the uterine reaction to AI in certain parts of the uterus., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The uterus exhibits intermittent electrophysiological activity in vivo. Although most active during labor, the non-pregnant uterus can exhibit activity of comparable magnitude to the early stages of labor. In this study, two types of flexible electrodes were utilized to measure the electrical activity of uterine smooth muscle in vivo in anesthetized, non-pregnant rats. Flexible printed circuit electrodes were placed on the serosal surface of the uterine horn of six anesthetized rats. Electrical activity was recorded for a duration of 20-30 min. Activity contained two components: high frequency activity (bursts) and an underlying low frequency 'slow wave' which occurred concurrently. These components had dominant frequencies of 6.82 ± 0.63 Hz for the burst frequency and 0.032 ± 0.0055 Hz for the slow wave frequency. There was a mean burst occurrence rate of 0.76 ± 0.23 bursts per minute and mean burst duration of 20.1 ± 6.5 s. The use of multiple high-resolution electrodes enabled 2D mapping of the initiation and propagation of activity along the uterine horn. This in vivo approach has the potential to provide the organ level detail to help interpret non-invasive body surface recordings., (© 2024. The Author(s).)

Background: A fine balance of feto-maternal resource allocation is required to support pregnancy, which depends on interactions between maternal and fetal genetic potential, maternal nutrition and environment, endometrial and placental functions. In particular, some imprinted genes have a role in regulating maternal-fetal nutrient exchange, but few have been documented in the endometrium. The aim of this study is to describe the expression of 42 genes, with parental expression, in the endometrium comparing two extreme breeds: Large White (LW); Meishan (MS) with contrasting neonatal mortality and maturity at two days of gestation (D90-D110). We investigated their potential contribution to fetal maturation exploring genes-fetal phenotypes relationships. Last, we hypothesized that the fetal genome and sex influence their endometrial expression. For this purpose, pure and reciprocally crossbred fetuses were produced using LW and MS breeds. Thus, in the same uterus, endometrial samples were associated with its purebred or crossbred fetuses., Results: Among the 22 differentially expressed genes (DEGs), 14 DEGs were differentially regulated between the two days of gestation. More gestational changes were described in LW (11 DEGs) than in MS (2 DEGs). Nine DEGs were differentially regulated between the two extreme breeds, highlighting differences in the regulation of endometrial angiogenesis, nutrient transport and energy metabolism. We identified DEGs that showed high correlations with indicators of fetal maturation, such as ponderal index at D90 and fetal blood fructose level and placental weight at D110. We pointed out for the first time the influence of fetal sex and genome on endometrial expression at D90, highlighting AMPD3, CITED1 and H19 genes. We demonstrated that fetal sex affects the expression of five imprinted genes in LW endometrium. Fetal genome influenced the expression of four genes in LW endometrium but not in MS endometrium. Interestingly, both fetal sex and fetal genome interact to influence endometrial gene expression., Conclusions: These data provide evidence for some sexual dimorphism in the pregnant endometrium and for the contribution of the fetal genome to feto-maternal interactions at the end of gestation. They suggest that the paternal genome may contribute significantly to piglet survival, especially in crossbreeding production systems., (© 2024. The Author(s).)

There is a suggested pathophysiology associated with endometrial microbiota in cases where repeated implantation failure of high-quality embryos is observed. However, there is a suspected association between endometrial microbiota and the pathogenesis of implantation failure. However, there is still a lack of agreement on the fundamental composition of the physiological microbiome within the uterine cavity. This is primarily due to various limitations in the studies conducted, including small sample sizes and variations in experimental designs. As a result, the impact of bacterial communities in the endometrium on human reproduction is still a subject of debate. In this discourse, we undertake a comprehensive examination of the existing body of research pertaining to the uterine microbiota and its intricate interplay with the process of embryo implantation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article. Competing interests There is no conflict of interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Women's health concerns are generally underrepresented in basic and translational research, but reproductive health in particular has been hampered by a lack of understanding of basic uterine and menstrual physiology. Menstrual health is an integral part of overall health because between menarche and menopause, most women menstruate. Yet for tens of millions of women around the world, menstruation regularly and often catastrophically disrupts their physical, mental, and social well-being. Enhancing our understanding of the underlying phenomena involved in menstruation, abnormal uterine bleeding, and other menstruation-related disorders will move us closer to the goal of personalized care. Furthermore, a deeper mechanistic understanding of menstruation-a fast, scarless healing process in healthy individuals-will likely yield insights into a myriad of other diseases involving regulation of vascular function locally and systemically. We also recognize that many women now delay pregnancy and that there is an increasing desire for fertility and uterine preservation. In September 2018, the Gynecologic Health and Disease Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development convened a 2-day meeting, "Menstruation: Science and Society" with an aim to "identify gaps and opportunities in menstruation science and to raise awareness of the need for more research in this field." Experts in fields ranging from the evolutionary role of menstruation to basic endometrial biology (including omic analysis of the endometrium, stem cells and tissue engineering of the endometrium, endometrial microbiome, and abnormal uterine bleeding and fibroids) and translational medicine (imaging and sampling modalities, patient-focused analysis of menstrual disorders including abnormal uterine bleeding, smart technologies or applications and mobile health platforms) to societal challenges in health literacy and dissemination frameworks across different economic and cultural landscapes shared current state-of-the-art and future vision, incorporating the patient voice at the launch of the meeting. Here, we provide an enhanced meeting report with extensive up-to-date (as of submission) context, capturing the spectrum from how the basic processes of menstruation commence in response to progesterone withdrawal, through the role of tissue-resident and circulating stem and progenitor cells in monthly regeneration-and current gaps in knowledge on how dysregulation leads to abnormal uterine bleeding and other menstruation-related disorders such as adenomyosis, endometriosis, and fibroids-to the clinical challenges in diagnostics, treatment, and patient and societal education. We conclude with an overview of how the global agenda concerning menstruation, and specifically menstrual health and hygiene, are gaining momentum, ranging from increasing investment in addressing menstruation-related barriers facing girls in schools in low- to middle-income countries to the more recent "menstrual equity" and "period poverty" movements spreading across high-income countries. [ABSTRACT FROM AUTHOR]

Evidence has been limited on the effect of mother-infant skin-to-skin contact on the involution process and maternal postpartum fatigue. This study aimed to determine such effects in a randomized controlled trial conducted in a hospital in Sivas, Turkey. Seventy-five women were randomized into one of two groups. The Mother-Infant Information Form, Involution Process Evaluation Form and Visual Analogue Scale for Fatigue were used to collect data between October 1, 2015 and May 1, 2016. Repeated Measures ANOVAs were used for data analyzes. In the intervention group, routine care and mother-to-infant skin-to-skin contact were provided for 30 minutes in first postnatal hour. In the control group, routine care was provided. At the postnatal second, fourth and 24th hours, fundus heights were 13.4 ± 0.3, 12.9 ± 0.3 and 11.8 ± 0.3 cm, respectively, in the intervention group, and 14.4 ± 0.4, 13.8 ± 0.3 and 12.9 ± 0.3 cm in the control group (p <.05). At the 24th hour, women in the intervention group had higher mean energy levels (29.8 ± 10.1) than the control group (25.1 ± 10.0) (p <.05), and fatigue score, amount of lochia and number of pads were statistically similar between the groups (p >.05). Mothers expressed satisfaction with skin-to-skin practice. Thus, mother-to-infant skin-to-skin contact can be used as a care practice in the postpartum period. [ABSTRACT FROM AUTHOR]

Background/Aim: It was hypothesized that testosterone could affect the distribution and expression of connexin 26 and connexin 43 in the uterus. Thus, the effects of testosterone on these parameters in the uterus during the uterine receptivity period were investigated. Materials and Methods: Intact pregnant rats were administered 1 mg/kg/day testosterone alone or in combination with flutamide, finasteride or anastrozole, subcutaneously on day1 of pregnancy till day 3. The rats were sacrificed at day 4 of pregnancy, which was considered as the uterine receptivity period for determining the expression and distribution of connexin 26 and connexion 43 by immunohistochemistry and quantitative polymerase chain reaction, respectively. Results: Treatment with 1 mg/kg/day testosterone increased connexin 26 and decreased connexin 43 mRNA expression and protein distribution in the uterus of early pregnancy rats. Conclusion: Changes in the uterine connexin 26 and connexin 43 expression by testosterone could disrupt embryo implantation, resulting in early pregnancy loss. [ABSTRACT FROM AUTHOR]

One of the main problems in obstetrics is uterine prolapse in cattle. In this study, developed a new method of treating this case, by inserting rubber ball deep into a uterine horn of an animal suffering from uterine prolapse. When used this method, the prolapse was completely recovery in 15/18 cows. In conclusions the treated cows by Uterine Rubber Ball method, have a good prognosis, the technique has a low cost and easy to apply. [ABSTRACT FROM AUTHOR]

Uterine activity impacts fetal and neonatal outcomes. The value of analysis of contraction frequency and the duration of the resting interval were underappreciated until the last two decades. Misconceptions about electronic fetal monitoring and the cesarean section rate may be related to the lack of early research on the significant impact of abnormal uterine activity. [ABSTRACT FROM AUTHOR]

The major histocompatibility complex (MHC) influences sexual selection in various vertebrates. Recently, MHC-linked social signaling was also shown to influence female fertility in horses (Equus caballus) diagnosed 17 days after fertilization. However, it remained unclear at which stage the pregnancy was terminated. Here we test if MHC-linked cryptic female choice in horses happens during the first days of pregnancy, i.e., until shortly after embryonic entrance into the uterus and before fixation in the endometrium. We exposed estrous mares to one of several unrelated stallions, instrumentally inseminated them with semen of another stallion, and flushed the uterus 8 days later to test for the presence of embryos. In total 68 embryos could be collected from 97 experimental trials. This success rate of 70.1% was significantly different from the mean pregnancy rate of 45.7% observed 17 days after fertilization using the same experimental protocol but without embryo flushing. Embryo recovery rate was not significantly dependent on whether the mares had been socially exposed to an MHC-dissimilar or an MHC-similar stallion. These observations suggest that MHC-linked maternal strategies affect embryo survival mainly (or only) during the time of fixation in the uterus. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to identify the existence of uterine micro-peristalsis (UMP) by dynamic ultrasound features and evaluate the feasibility of UMP as a tool to distinguish pregnant and non-pregnant infertility patients undergoing in vitro fertilization-embryo transfer (IVF-ET), using clinical pregnancy results as a benchmark.Methods: Fifty-one women, including 29 pregnant and 22 non-pregnant patients were recruited. Also, ultrasound videos were collected before embryo transfer. First of all, undiscoverable uterine micro-peristalsis was magnified by video magnification. Then, the dynamic features of UMP were characterized by a novel index termed histogram entropy based on the micro-peristalsis feature selection by entropy weight (HEMEW), which was generated by combining frame difference and volume local phase quantization. Finally, a comparative experiment of HEMEW between non-pregnant and pregnant patients, logistic regression analysis for HEMEW and other independent clinical characteristics, and receiver operating characteristic (ROC) analysis were performed.Results: The magnified uterine video clearly exhibited UMP, which was invisible in the original ultrasound video. Further, there existed a significant difference in HEMEW between pregnant patients and non-pregnant patients after micro-motion magnification (p = 0.003, n = 51). The logistic regression result showed that HEMEW (p = 0.006) was significantly associated with clinical pregnancy outcome, while other independent variables had no significant effect on it. The ROC performance of HEMEW was 72.6% accuracy (AUC = 0.774, 95% CI: 0.644-0.905).Conclusions: The proposed micro-motion magnification and characterization strategy identified the existences of uterine micro-peristalsis, and verified that UMP has the feasibility to distinguish the outcomes of IVF-ET. [ABSTRACT FROM AUTHOR]

Obesity can have a significant impact on pregnancy outcomes by compromising the ability of the uterus to relax, which increases the likelihood of conditions such as preterm labor. One of the key pathways responsible for uterine relaxation is the β-adrenergic signaling pathway, and it is well-documented that obesity, often linked to a high-fat diet, can disrupt this pathway within the uterine environment. Hyperleptinemia is a significant feature of pregnancy as well as obesity. However, the effect of leptin on β-adrenergic signaling pathway has not been studied. In the present study, we studied the effects of leptin on transcriptions of the major proteins defining the β-adrenergic signaling pathway in pregnant rat uterus. Leptin treatment at a supraphysiological concentration to pregnant rat uterine strips increased the mRNA and protein expressions of Gs protein but not the mRNA of β 2 - and β 3 -adrenoceptors. It also enhanced the expression of Gi-protein, but not the Gq protein. Nevertheless, the mRNA ratio of Gs to Gi protein experienced a significant decrease. Further, leptin reduced the transcription of BK Caα and BK Caβ channel subunits. In leptin-stimulated tissues, there was also an increase in the expression of leptin receptor and JAK-2. In conclusion, leptin decreases the ratio of Gs to Gi proteins and BK Caα and BK Caβ channel subunits suggesting hyperleptinemia is a likely factor inducing uterine relaxant dysfunction in obesity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Reproductive issues are becoming an increasing global problem. There is increasing interest in the relationship between microbiota and reproductive health. Stable microbiota communities exist in the gut, reproductive tract, uterus, testes, and semen. Various effects (e.g., epigenetic modifications, nervous system, metabolism) of dysbiosis in the microbiota can impair gamete quality; interfere with zygote formation, embryo implantation, and embryo development; and increase disease susceptibility, thus adversely impacting reproductive capacity and pregnancy. The maintenance of a healthy microbiota can protect the host from pathogens, increase reproductive potential, and reduce the rates of adverse pregnancy outcomes. In conclusion, this review discusses microbiota in the male and female reproductive systems of multiple animal species. It explores the effects and mechanisms of microbiota on reproduction, factors that influence microbiota composition, and applications of microbiota in reproductive disorder treatment and detection. The findings support novel approaches for managing reproductive diseases through microbiota improvement and monitoring. In addition, it will stimulate further systematic explorations of microbiota-mediated effects on reproduction.

High rates of early pregnancy loss are a critical issue in dairy herds, particularly in seasonal, grazing systems. Components of the uterine luminal fluid (ULF), on which the early embryo depends for sustenance and growth, partly determine early pregnancy losses. Here, changes in ULF from early to mid-postpartum in crossbred dairy cows were explored, linking them with divergent embryo development. For this, the uteri of 87 cows at Day 7 of pregnancy at first and third estrus postpartum were flushed to collect ULF. Eighteen metabolites (chiefly organic acids and sugars) significantly varied in abundance across postpartum, indicating a molecular signature of physiological recovery consistent of the upregulation of pyrimidine metabolism and glycerophospholipid metabolism, and downregulation of pentose phosphate and taurine metabolism pathways. Joint pathway analysis of metabolomics data and a previously generated proteomics data set on the same ULF samples suggests key links between postpartum recovery and subsequent successful embryo development. These include upregulation of VEGFA and downregulation of metabolism, NRF2, T-cell receptor, which appear to improve the ULF's capacity of sustaining normal embryo development, and a putative osmo-protectant role of beta-alanine. These relationships should be further investigated to develop tools to detect and reduce early pregnancy loss in dairy cows., (© 2023 The Authors. Molecular Reproduction and Development published by Wiley Periodicals LLC.)