[Analysis of Reproductive Tract Microecological Changes During the Frozen-Thawed Embryo Transfer Cycle and Clinical Pregnancy Outcomes]. / æ¿€ç´ æ›¿ä»£å†»èƒšç§»æ¤å‘¨æœŸç”Ÿæ®–é“å¾®ç”Ÿæ€å˜åŒ–ä¸Žå¦Šå¨ ç»“å±€åˆ†æž.

Objective: This study aims to analyze the relationship between reproductive tract microecological changes, metabolic differences, and pregnancy outcomes at different time points in the frozen-thawed embryo transfer cycle while patients are undergoing hormone replacement therapy, which will be a breakthrough point for improving outcomes. Methods: A total of 20 women undergoing frozen-thawed single blastocyst transfer for the first time at the Reproductive Medicine Center of Fujian Maternal and Child Health Hospital between July 2022 and January 2023 were recruited for this study. Their vaginal and cervical secretions were collected for 16S rRNA sequencing and non-targeted metabolomics analysis on days 2-5 of menstruation, day 7 after estrogen replacement therapy started, the day when progesterone was added, and the day of transplantation. The subjects were divided into different groups according to their clinical pregnancy status and the sequencing results were analyzed using bioinformatics methods. Results: 1) The alpha-diversity index of the vaginal and cervical microbiota was higher on days 2-5 of menstruation (P<0.01), but did not differ significantly on day 7 after oral estrogen replacement therapy started, the day of progesterone administration, and the day of transplantation (P≥0.1). 2) Both the pregnant group and the non-pregnant group showed a variety of microorganisms and metabolites with significant differences in the lower reproductive tract at different time points. 3) Microbial analysis at different time points showed that there were significant differences in vaginal flora, including Peptoniphilus, Enterocloster, Finegoldia, Klebsiella, Anaerobutyricum, Agathobaculum, Sporanaerobacter, Bilophila, Prevotella, and Anaerococcus in the pregnant group (P<0.05). 4) Metabolite analysis at different time points showed that there were significant differences in 3-hydroxybenzoic acid, linatine, (R)-amphetamine, hydroxychloroquine, and L-altarate in the vaginal secretions of the pregnant group (P<0.05), and that there were significant differences in isocitric acid, quassin, citrinin, and 12(R)-HETE in the cervical secretions (P<0.05). 5) Metabolite analysis at different time points showed that, in the non-pregnant group, there were significant differences in linatine, decanoyl-L-carnitine, aspartame, sphingosine, and hydroxychloroquine in the vaginal secretions (P<0.05), and the isocitric acid, quassin, ctrinin, and 12(R)-HETE in the cervical secretions (P<0.05). 6) Combined microbiome and metabolomics analysis showed that certain metabolites were significantly associated with microbial communities, especially Klebsiella. Conclusions: Significant differences in the microbiota genera and metabolites at different time points were found during the frozen-embryo transfer cycle of hormone replacement therapy, which may be used as potential biomarkers to predict pregnancy outcomes of embryo transfer.

In Vitro Culture of Mammalian Embryos: Is There Room for Improvement?

Preimplantation embryo culture, pivotal in assisted reproductive technology (ART), has lagged in innovation compared to embryo selection advancements. This review examines the persisting gap between in vivo and in vitro embryo development, emphasizing the need for improved culture conditions. While in humans this gap is hardly estimated, animal models, particularly bovines, reveal clear disparities in developmental competence, cryotolerance, pregnancy and live birth rates between in vitro-produced (IVP) and in vivo-derived (IVD) embryos. Molecular analyses unveil distinct differences in morphology, metabolism, and genomic stability, underscoring the need for refining culture conditions for better ART outcomes. To this end, a deeper comprehension of oviduct physiology and embryo transport is crucial for grasping embryo-maternal interactions' mechanisms. Research on autocrine and paracrine factors, and extracellular vesicles in embryo-maternal tract interactions, elucidates vital communication networks for successful implantation and pregnancy. In vitro, confinement, and embryo density are key factors to boost embryo development. Advanced dynamic culture systems mimicking fluid mechanical stimulation in the oviduct, through vibration, tilting, and microfluidic methods, and the use of innovative softer substrates, hold promise for optimizing in vitro embryo development.

Genome Sequence Comparisons between Small and Large Colony Phenotypes of Equine Clinical Isolates of Arcanobacterium hippocoleae.

Arcanobacterium hippocoleae is a Gram-positive fastidious bacterium and is occasionally isolated from the reproductive tract of apparently healthy mares (Equus caballus) or from mares with reproductive tract abnormalities. Apart from a few 16S rRNA gene-based GenBank sequences and one recent report on complete genome assembly, detailed genomic sequence and clinical experimental data are not available on the bacterium. Recently, we observed an unusual increase in the detection of the organism from samples associated with mare reproductive failures in Atlantic Canada. Two colony morphotypes (i.e., small, and large) were detected in culture media, which were identified as A. hippocoleae by MALDI-TOF mass spectrometry and 16S rRNA gene sequencing. Here, we report the whole genome sequencing and characterization of the morphotype variants. The genome length of the large phenotypes was between 2.42 and 2.43, and the small phenotype was 1.99 Mbs. The orthologous nucleotide identity between the large colony phenotypes was ~99%, and the large and small colony phenotypes was between 77.86 and 78.52%, which may warrant the classification of the two morphotypes into different species. Phylogenetic analysis based on 16S rRNA genes or concatenated housekeeping genes grouped the small and large colony variants into two different genotypic clusters. The UvrA protein, which is part of the nucleotide excision repair (NER) system, and 3-isopropoylmalate dehydratase small subunit protein expressed by the leuD gene were identified as potential virulence factors in the large and small colony morphotypes, respectively. However, detailed functional studies will be required to determine the exact roles of these and other identified hypothetical proteins in the cellular metabolism and potential pathogenicity of A. hippocoleae in mares.

Three-dimensional analysis of partial restoration of spermatogenesis in vitamin A-deficient mice.

BACKGROUND: An animal model of the partial restoration of spermatogenesis may be useful in the field of reproductive biology and medicine. Vitamin A deficiency (VAD) induces the restorable arrest of spermatogenesis at the level of spermatogonia and is used as a mouse model of spermatogenesis disorder. OBJECTIVE: We aimed to establish an animal model in which spermatogenesis is partially restored by switching a vitamin A deficiency diet to a normal vitamin A-containing diet and conduct a comprehensive analysis to identify vulnerable sites in the seminiferous tubules that affect the efficient restoration of spermatogenesis in this model. MATERIALS AND METHODS: Mice fed a vitamin A deficiency diet until 12 weeks old and then reared with a normal diet for 15 weeks served as the restoration model. We performed three-dimensional reconstructions of the seminiferous tubules and analyzed the three-dimensional distribution of restored spermatogenesis throughout the testis. RESULTS: Fifteen weeks after the switch to the normal diet, spermatogenesis was restored in 78% of the length of seminiferous tubules. The percentage of restored spermatogenesis was lower in longer seminiferous tubules. An analysis of the distribution of spermatogenesis throughout the testis in this model revealed that it was restored less in portions of seminiferous tubules near the rete testis and hairpin curves and also in those located in the caudal region of the testis. These sites tended to correspond to sites with fewer spermatogonia in the vitamin A deficiency testis. DISCUSSION AND CONCLUSIONS: We established an animal model of the partial restoration of spermatogenesis and examined the three-dimensional distribution of restored spermatogenesis in seminiferous tubules. The results obtained provide insights into the mechanisms underlying spermatogenesis disorders and may contribute to better clinical practices, such as the screening of drugs or therapeutic interventions for human male infertility and improvements in fertility preservation techniques for individuals undergoing chemotherapy.

Myxofibrosarcoma of the penis in an African pygmy hedgehog (Atelerix albiventris) - A clinical case.

A 3-year-old, 420 g, intact male African pygmy hedgehog (Atelerix albiventris) was presented with a sudden appearance of a mass protruding from its preputium. A detailed physical examination revealed the presence of a polyp-like mass, connected to the mucous membrane of the penis and a second, multilobular mass with a larger base. Both masses were surgically removed. While the histopathological examination of the polyp-like mass revealed only a chronic active inflammatory reaction, the histopathological examination of the multilobular mass revealed a tumorous tissue composed of spindle-shaped cells, irregularly oval or polygonal in some places. Focal tumour cells with a myxoid differentiation were observed in the greater part of this tumour. The stroma was made up of sparse fibrous tissue. The surface epithelium was hyperplastic with ulcerations and necrosis. The tumour was classified as a myxofibrosarcoma. Two weeks post-surgery, the patient did not show any clinical signs of the presented disease. According to our knowledge, this is the first published case of the surgical treatment of penile myxofibrosarcoma in an African pygmy hedgehog.

The Role of the Human Microbiome in Epithelial Ovarian Cancer.

Ovarian cancer is the fifth-leading cause of cancer deaths among women due to the absence of available screening methods to identify early disease. Thus, prevention and early disease detection investigations are of high priority, surrounding a critical window of opportunity to better understand important pathogenic mechanisms of disease progression. Microorganisms modulate molecular interactions in humans that can influence states of health and disease, including ovarian cancer. While the mechanisms of infectious microbial invasion that trigger the immune-inflammatory axis are well studied in cancer research, the complex interactions that promote the transition of noninfectious healthy microbes to pathobiont expansion are less understood. As traditional research has focused on the influences of infectious pathogens on ovarian cancer development and progression, the impact of noninfectious microbes has gained scientific attention. The objective of this chapter is to summarize current evidence on the role of microbiota in epithelial ovarian cancer throughout disease.

Impact of COVID-19 on Profession and Health of Female Sex Workers: Apprehension, Acquiescence, and Resilience.

In Surat city of Gujarat, India, female sex workers (FSW)-based targeted interventions (TI) and community-based organizations (CBO) have been functioning since 1998. To document the impact of the COVID-19 lockdown (March-May 2020) on FSWs and STI/RTI/HIV preventive measures provided through TI/CBOs in Surat city, sequential, explanatory mixed-methods design was used. We conducted a desk review of quarterly programmatic data (2018-2020) of four TIs and CBOs and interviewed of 221 FSWs to study pre- and post-lockdown socioeconomic conditions, engagement in sex work, health services during COVID-19 lockdown and coping strategies, followed by five focus group discussions of FSWs and TI/CBO project staff. Study identified four major themes: reasons for working as a FSW during COVID-19 lockdown, entry to sex work during or as a consequence of lockdown, exploitation of FSWs during lockdown, and challenges of TI and CBOs in service provision in pandemic situation. Number of new registrations and STI/RTI detection increased immediately after lockdown. TI/CBO and other NGOs working for women welfare must build financial independence by training them in microeconomics, savings, and entrepreneurship. TI/CBO staff must also include experts in finance or business, trained in emergency response. The presence of strong TI/CBO network facilitated prompt delivery of essential commodities and financial aid to FSWs. However, laboratory and screening services were hampered, which warrants need of introducing self-test kits. In backdrop of decrease in condom distribution, continuation of sex work during lockdown and disruption of routine HIV/STI/RTI screening facilities, our study also recommends intensified HIV/STI/RTI screening among FSWs.

Insights into the Microbial Composition of Intratumoral, Reproductive Tract, and Gut Microbiota in Ovarian Cancer Patients.

According to the latest global cancer data, ovarian cancer is the deadliest among all gynecological malignant tumors and ranks fifth in terms of mortality. Its etiology and pathogenesis are unknown, and the 5-year survival rate of patients with advanced ovarian cancer is only 40% (Sung et al. CA Cancer J Clin 71:209-49, 2021). Recent research has shown that the human microbiota plays a crucial role in the development and progression of tumors, including ovarian cancer. Numerous studies have highlighted the complex connections between the reproductive tract microbiota, intestinal microbiota, and ovarian cancer (Jacobson et al. PeerJ 9:e11574, 2021). Therefore, this chapter will delve into composition, function, and the correlation between microbiota and immunity in the field of ovarian cancer microbiota, as well as the potential of bacteria in therapeutics and diagnostics of ovarian cancer.

Deciphering the role of female reproductive tract microbiome in reproductive health: a review.

Relevant studies increasingly indicate that female reproductive health is confronted with substantial challenges. Emerging research has revealed that the microbiome interacts with the anatomy, histology, and immunity of the female reproductive tract, which are the cornerstone of maintaining female reproductive health and preventing adverse pregnancy outcomes. Currently, the precise mechanisms underlying their interaction and impact on physiological functions of the reproductive tract remain elusive, constituting a prominent area of investigation within the field of female reproductive tract microecology. From this new perspective, we explore the mechanisms of interactions between the microbiome and the anatomy, histology, and immunity of the female reproductive tract, factors that affect the composition of the microbiome in the female reproductive tract, as well as personalized medicine approaches in managing female reproductive tract health based on the microbiome. This study highlights the pivotal role of the female reproductive tract microbiome in maintaining reproductive health and influencing the occurrence of reproductive tract diseases. These findings support the exploration of innovative approaches for the prevention, monitoring and treatment of female reproductive tract diseases based on the microbiome.

Commonality and heterogeneity of pacemaker mechanisms in the male reproductive organs.

During emission, the first phase of ejaculation, smooth muscle in organs of the male reproductive tract (MRT) vigorously contract upon sympathetic nerve excitation to expel semen consisting of sperm and seminal plasma. During inter-ejaculation phases, the epididymis, seminal vesicles and prostate undergo spontaneous phasic contractions (SPCs), this transporting and maintaining the quality of sperm and seminal plasma. Recent studies have revealed platelet-derived growth factor receptor α-expressing (PDGFRα+) subepithelial interstitial cells in seminal vesicles subserve the role of pacemaker cells that electrically drive SPCs in this organ. PDGFRα+ smooth muscle cells in the epididymis also appear to function as pacemaker cells implicating PDGFRα as a potential signature molecule in MRT pacemaking. The dominant mechanism driving pacemaking in these organs is the cytosolic Ca2+ oscillator. This operates through entrainment of the release-refill cycle of Ca2+ stores, the released Ca2+ ions opening Ca2+-activated chloride channels, including in some cases ANO1 (TMEM16A), with the resultant pacemaker potential activating L-type voltage-dependent Ca2+ channels in the smooth muscle causing contraction (viz. SPCs). A second pacemaker mechanism, namely the membrane oscillator also has a role in specific cases. Further investigations into the commonality and heterogeneity of MRT pacemakers will open an avenue for understanding the pathogenesis of male infertility associated with deterioration of seminal plasma.

Reproductive healthcare seeking behaviour of women of the reproductive age group in an urban resettlement area of district Gautam Buddh Nagar in Uttar Pradesh, India.

Background: Reproductive tract infections (RTIs) and gynaecological morbidities constitute a significant proportion of morbidities in women of the reproductive age group. Objective: To find out the proportion of reproductive age group women in an urban resettlement colony having the symptoms of gynaecological morbidities and RTI/sexually transmitted infection (STI) and to explore the healthcare seeking behaviour of the women during such ailments. Materials and Methods: A community-based cross-sectional study was conducted from January to June 2023 among 317 females aged 15 to 49 years in an urban resettlement area of Gautam Buddh Nagar district in Uttar Pradesh. Statistical analysis used included descriptive statistics and Chi-square test. SPSS 23 was used for data analysis. Results: There was a prevalence of 65.3% of at least one self-reported symptom suggestive of RTI/STI or gynaecological morbidity among the respondents. Among the symptomatic respondents, 54.1% were found to seek treatment. Among the reasons given for not seeking treatment in any health facility, the majority (83.1%) responded 'lack of awareness that the problem needed medical treatment' and 'stigma related with the problem' to be the main reasons. Conclusion: The reproductive healthcare seeking behaviour was found to be inadequate, with only 54.1% of symptomatic respondents seeking treatment. Enhanced health awareness sessions can be planned in the short term, and skilled communicators within or outside of the health system in the long term may be deployed to disseminate information in the community regarding sexual and gynaecological morbidities in reproductive age group women and their timely intervention.

Aerobic vaginitis, bacterial vaginosis, and vaginal candidiasis among women of reproductive age in Arba Minch, southern Ethiopia.

Reproductive tract infections (RTIs) are a persistent public health threat worldwide, particularly among women in low-income countries of Africa, including Ethiopia, where drug resistance is also a growing problem. It is crucial to address this problem to ensure women's health and well-being. A cross-sectional study was carried out among a cohort of 398 women of reproductive age who sought medical attention at the Gynecology Department of the Arba Minch General Hospital, southern Ethiopia, from January to June 2020. They were chosen through systematic random sampling, and a pre-tested structured questionnaire was used to collect the data. The collection of vaginal and/or cervical swabs were done to diagnose bacterial vaginosis (BV) and aerobic vaginitis (AV) using Nugent and AV score analyses, respectively. The swabs were subjected to standard microbiological culture techniques to detect the isolates causing AV and vaginal candidiasis (VC). The susceptibility profiles of the causative agents of AV were checked by the Kirby-Bauer disc diffusion technique. Descriptive and inferential statistical analyses were also done. Aerobic vaginitis was the predominantly diagnosed RTI (n = 122, 30.7%), followed by BV (n = 117, 29.4%) and VC (n = 111, 27.9%). The prominent bacteria of AV were Escherichia coli (n = 36, 34.2%) and Klebsiella pneumoniae (n = 30, 28.5%). The overall rate of multidrug-resistant (MDR) bacteria was 65.71% (n = 69). History of abortion (p = 0.01; AOR = 4.0, 95% CI = 2.1, 7.7) and the habit of using vaginal pH-altering contraceptives (p = 0.01; AOR = 4.7, 95% CI = 2.5, 8.8) have the greatest odds of RTI. The high prevalence of RTIs in our study warrants an urgent intervention to minimize the associated morbidities and complications. The overall rate of MDR bacterial isolates necessitates the implementation of an effective surveillance program in the study setting.

Comparison of Siglec-1 protein networks and expression patterns in sperm and male reproductive tracts of mice, rats, and humans.

Background: Sialic acid-binding immunoglobulin-like lectin 1 (Siglec-1) is a transmembrane glycoprotein involved in the sialic acid (Sia)-dependent regulation of the immune system. Siglec-1 expression has recently been identified in the male reproductive tract (MRT) of several species, including humans, cattle, horses, and sheep, and may play a role in modulating fertility in a Sia-dependent manner. Materials and Methods: In this study, protein-protein interaction (PPI) analysis of Siglec-1 was conducted to identify associated network protein conservation, and the expression of Siglec-1 in the MRT of mice and rats, including their accessory sex glands and spermatozoa was determined by immunostaining. Results: Network analysis of proteins with Siglec-1 in mice and rats demonstrated significant similarity to human Siglec-1 networks, suggesting a similar conservation of network proteins between these species and, hence, a potential conservation role in immune modulation and function. Specific immunostaining patterns of mouse and rat testes, epididymis, ductus deferens, accessory sex gland tissues, and sperm were detected using human Siglec-1. These results confirmed that the human Siglec-1 antibody could cross-react with mouse and rat Siglec-1, suggesting that the specific expression patterns of Siglec-1 in the MRT and sperm of both mice and rats are similar to those observed in other species. Conclusions: The conservation of Siglec-1 expression patterns in sperm and within the MRT and the similarity of protein networks for Siglec-1 across species suggest that Siglec-1 may function in a similar manner across species. These results also suggest that rodents may serve as a valuable model system for exploring the function of Siglecs in the reproductive system across species and their potential role in modulating fertility in a Sia-dependent manner.

Urinary and reproductive tract infection symptoms and menstrual hygiene practices in refugee camps in Jordan: A cross-sectional study.

BACKGROUND: Urinary tract infections and reproductive tract infections pose significant health risks, particularly among women living in challenging conditions. Unhygienic menstrual practices can exacerbate these risks, impacting physical and psychological well-being. OBJECTIVES: This study assessed the association between unhygienic menstrual care and self-reported urinary tract infection/reproductive tract infection symptoms among refugee women. In addition, it explored the association between these symptoms and mental health, specifically depressive symptoms. DESIGN: This study adopted a cross-sectional observational design. METHODS: This study was conducted between January and March 2023, involving 387 reproductive-age refugee women. Data collected included sociodemographic information and urinary tract infection/reproductive tract infection symptoms. In addition, we used the Menstrual Practice Needs Scale to evaluate menstrual hygiene practices and the Patient Health Questionnaire-9 for depressive symptoms. Statistical analysis was performed using Python version 3.9.12. RESULTS: Of 387 refugee women, 92.25% reported having urinary or reproductive tract infection symptoms in the previous 3 months. Factors like older age (odds ratio = 1.764, 95% confidence interval = 1.083-2.873, p-value = 0.023), lower family income (odds ratio = 0.327, 95% confidence interval = 0.138-0.775, p-value = 0.011), lower educational level (odds ratio = 0.222, 95% confidence interval = 0.068-0.718, p-value = 0.012), and being married (odds ratio = 0.328, 95% confidence interval = 0.188-0.574, p-value < 0.001) were significantly associated with urinary or reproductive tract infection risk. Difficulties obtaining menstrual products and thus reusing them increased the odds of urinary or reproductive tract infection diagnosis (odds ratio = 2.452, 95% confidence interval = 1.497-4.015, p-value < 0.001). Women with urinary or reproductive tract infection symptoms exhibited higher Patient Health Questionnaire-9 scores than those without (12.14 ± 5.87 vs 9.99 ± 5.86, p-value < 0.001, respectively). CONCLUSION: This study highlights a high prevalence of urinary or reproductive tract infection symptoms among refugee women residing in camps in Jordan, which was associated with poor menstrual hygiene practices and depressive symptoms. To reduce the urinary tract infection/reproductive tract infection burden in marginalized communities, public health initiatives should enhance healthcare accessibility, provide reproductive education, and promote holistic well-being practices for refugee women.

Comparative analysis of reproductive tract microbiomes in modern and slower-growing broiler breeder lines.

Introduction: The reproductive tract microbiome in hens is of interest because bacteria in the reproductive tract could potentially affect fertilization and egg production, as well as integrate into the forming egg and vertically transmit to progeny. Methods: The reproductive tract microbiome of 37-week-old modern commercial Cobb breeding dams was compared with that of dams from a broiler Legacy line which has not undergone selection since 1986. All animals were kept together under the same management protocol from day of hatch to avoid confounders. Results: In regards to reproductive abilities, Cobb dams' eggs weighed more and the magnum section of their reproductive tract was longer. In regards to microbiome composition, it was found that the reproductive tract microbiomes of the two lines had a lot in common but also that the two breeds have unique reproductive tract microbiomes. Specifically, the order Pseudomonadales was higher in the magnum of Legacy dams, while Verrucomicrobiales was lower. In the infundibulum, Lactobacillales were higher in the Legacy dams while Verrucomicrobiales, Bacteroidales, RF32 and YS2 were lower. Discussion: our results show that breeding programs have modified not only the physiology of the reproductive tract but also the reproductive tract microbiome. Additional research is required to understand the implications of these changes in the reproductive tract microbiome on the chicken host.

Case report: Synchronous tumors of the female reproductive tract in systemic lupus erythematosus: report of two cases and review of the literature.

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple systems. Patients with SLE are prone to a variety of malignancies, especially neoplasms of the female reproductive tract. Synchronous tumors, considered to involve multiple sites, are rare in the female reproductive tract. There are hardly any reports of SLE with synchronous reproductive tract tumors. Case presentation: We report the occurrence of two to three reproductive tract tumors in two women with SLE. A 52-year-old woman was diagnosed with vulvar cancer and cervical cancer. Another woman, aged 67, was diagnosed with concurrent vulvar cancer, vaginal cancer, and cervical cancer and also presented with a suspected lung cancer. Conclusion: The presence of synchronous tumors of the reproductive tract in patients with SLE is uncommon and can be easily disregarded. It is crucial to highlight that SLE patients with multiple primary malignancies exhibit notable late-stage presentation at the time of diagnosis, inadequate disease-free survival, poor overall survival, rapid progression rates, and mortality. Consequently, greater awareness must be raised regarding synchronous reproductive tract tumors in patients with SLE. Regular comprehensive cancer screening and management should be implemented for individuals diagnosed with SLE.

How sperm protects itself: A journey in the female reproductive system.

Sperm must pass a complex route in the female reproductive tract (FRT) to reach the fertilization site and join the oocyte. Thus, it should employ several mechanisms to survive against the female immune system, fertilize the oocyte, and successfully transmit paternal genes to the next generation. In addition to self-protection, sperm may be involved in the immune tolerance to the developing embryo and regulating the FRT for embryo implantation and subsequent pregnancy. Hence, this review intends to summarize the mechanisms that protect sperm in the FRT: including immunomodulatory factors that are carried by seminal plasma, cell-to-cell and molecular interaction of sperm with epithelial and immune cells of the FRT, high regulated secretions of inflammatory factors such as cytokines, chemokines, and growth factors, inducing immune tolerance to paternal antigens, and specialized expression of cell receptors and binding proteins. In most of these events sperm induces the FRT to protect itself by modulating immune responses for its own benefit. However, not all sperm in the semen are able to trigger the survival mechanisms and only high-quality sperm will overcome this challenge. A clear understanding of the molecular mechanisms that maintain sperm viability and function in the FRT can lead to new knowledge about infertility etiology and a new approach in assisted reproductive technologies for the preparation and selection of the best sperm based on the criteria that physiologically happen in-vivo.

Health benefits of combined oral contraceptives - a narrative review.

PURPOSE: This review presents an update of the non-contraceptive health benefits of the combined oral contraceptive pill. METHODS: We conducted a literature search for (review) articles that discussed the health benefits of combined oral contraceptives (COCs), in the period from 1980 to 2023. RESULTS: We identified 21 subjective and/or objective health benefits of COCs related to (i) the reproductive tract, (ii) non-gynaecological benign disorders and (iii) malignancies. Reproductive tract benefits are related to menstrual bleeding(including anaemia and toxic shock syndrome), dysmenorrhoea, migraine, premenstrual syndrome (PMS), ovarian cysts, Polycystic Ovary Syndrome (PCOS), androgen related symptoms, ectopic pregnancy, hypoestrogenism, endometriosis and adenomyosis, uterine fibroids and pelvic inflammatory disease (PID). Non-gynaecological benefits are related to benign breast disease, osteoporosis, rheumatoid arthritis, multiple sclerosis, asthma and porphyria. Health benefits of COCs related to cancer are lower risks of endometrial cancer, ovarian cancer and colorectal cancer. CONCLUSIONS: The use of combined oral contraceptives is accompanied with a range of health benefits, to be balanced against its side-effects and risks. Several health benefits of COCs are a reason for non-contraceptive COC prescription.

MAP3K1 regulates female reproductive tract development.

Mitogen-activated protein 3 kinase 1 (MAP3K1) has a plethora of cell type-specific functions not yet fully understood. Herein, we describe a role for MAP3K1 in female reproductive tract (FRT) development. MAP3K1 kinase domain-deficient female mice exhibited an imperforate vagina, labor failure and infertility. These defects corresponded with shunted Müllerian ducts (MDs), the embryonic precursors of FRT, that manifested as a contorted caudal vagina and abrogated vaginal-urogenital sinus fusion in neonates. The MAP3K1 kinase domain is required for optimal activation of the Jun-N-terminal kinase (JNK) and cell polarity in the MD epithelium, and for upregulation of WNT signaling in the mesenchyme surrounding the caudal MD. The MAP3K1-deficient epithelial cells and MD epithelium had reduced expression of WNT7B ligands. Correspondingly, conditioned media derived from MAP3K1-competent, but not -deficient, epithelial cells activated a TCF/Lef-luciferase reporter in fibroblasts. These observations indicate that MAP3K1 regulates MD caudal elongation and FRT development, in part through the induction of paracrine factors in the epithelium that trans-activate WNT signaling in the mesenchyme.