Predicting Infertility: How Genetic Variants in Oocyte Spindle Genes Affect Egg Quality.

Successful reproduction relies on the union of a single chromosomally normal egg and sperm. Chromosomally normal eggs develop from precursor cells, called oocytes, that have undergone accurate chromosome segregation. The process of chromosome segregation is governed by the oocyte spindle, a unique cytoskeletal machine that splits chromatin content of the meiotically dividing oocyte. The oocyte spindle develops and functions in an idiosyncratic process, which is vulnerable to genetic variation in spindle-associated proteins. Human genetic variants in several spindle-associated proteins are associated with poor clinical fertility outcomes, suggesting that heritable etiologies for oocyte dysfunction leading to infertility exist and that the spindle is a crux for female fertility. This chapter examines the mammalian oocyte spindle through the lens of human genetic variation, covering the genes TUBB8, TACC3, CEP120, AURKA, AURKC, AURKB, BUB1B, and CDC20. Specifically, it explores how patient-identified variants perturb spindle development and function, and it links these molecular changes in the oocyte to their cognate clinical consequences, such as oocyte maturation arrest, elevated egg aneuploidy, primary ovarian insufficiency, and recurrent pregnancy loss. This discussion demonstrates that small genetic errors in oocyte meiosis can result in remarkably far-ranging embryonic consequences, and thus reveals the importance of the oocyte's fine machinery in sustaining life.

Secretion of WNT7A by UC-MSCs assist in promoting the endometrial epithelial regeneration.

Stem cell therapy for intrauterine adhesions (IUAs) has been widely used in clinical treatment. However, intravenous injection lacks sufficient targeting capabilities, while in situ injection poses challenges in ensuring the effective survival of stem cells. Furthermore, the mechanism underlying the interaction between stem cells and endometrial cells in vivo remains poorly understood, and there is a lack of suitable in vitro models for studying these problems. Here, we designed an extracellular matrix (ECM)-adhesion mimic hydrogel for intrauterine administration, which was more effective than direct injection in treating IUAs. Additionally, we analyzed the epithelial-mesenchymal transition (EMT) and confirmed that the activation of endometrial epithelial stem cells is pivotal. Our findings demonstrated that umbilical cord mesenchymal stem cells (UC-MSCs) secrete WNT7A to activate endometrial epithelial stem cells, thereby accelerating regeneration of the endometrial epithelium. Concurrently, under transforming growth factor alpha (TGFA) stimulation secreted by the EMT epithelium, UC-MSCs upregulate E-cadherin while partially implanting into the endometrial epithelium.

Influence of state-of-the-art laboratory techniques on the phenotyping of women with polycystic ovary syndrome in the clinical setting.

PURPOSE: Evidence-based guidelines for the management of polycystic ovary syndrome (PCOS) recommend clinical laboratories use liquid chromatography-tandem mass spectrometry (LC-MS/MS) for diagnosing biochemical hyperandrogenism. However, automated immunoassays are still mostly used in routine laboratories worldwide. Another hurdle for PCOS phenotyping in the clinical setting is ultrasound assessment of polycystic ovarian morphology. We address the impact of using state-of-the-art (LC-MS/MS) and of an anti-müllerian hormone (AMH) assay on the diagnosis of PCOS in routine practice. METHODS: In a cross-sectional study, we included 359 premenopausal women consecutively evaluated because of symptoms of functional androgen excess or hyperandrogenemia, and finally diagnosed with PCOS. Patients were submitted to routine phenotyping based on serum androgen measurements by immunoassays and an ovarian ultrasound when necessary. Samples of all patients were also assayed by LC-MS/MS for hyperandrogenemia and for circulating AMH. RESULTS: The observed agreement between immunoassays and LC-MS/MS in identifying hyperandrogenemia was poor [78.0%; k(95%CI): 0.366 (0.283;0.449)]. The observed agreement between ultrasound and increased AMH was 27.3% [(95%CI): 0.060 (0.005; 0.115)]. Using LC-MS/MS changed PCOS phenotypes in 60(15.8%) patients. Fifty-two (18.3%) individuals with hyperandrogenemia by routine immunoassays no longer presented with androgen excess by LC-MS/MS. Overall diagnostic agreement between routine assessment using immunoassays and ultrasound and that derived from LC-MS/MS and the addition of AMH to US was moderate [weighted κ (linear weights): 0.512 (0.416;0.608)]. CONCLUSIONS: Immunoassays used in routine practice are unacceptably inaccurate for phenotyping women with PCOS. Our data cast some doubts upon the interchangeability of serum AMH and ultrasound examination for the diagnosis of PCOS.

Sirenian (manatees and dugongs) reproductive endocrinology.

Reproductive hormones are essential to mating systems, behavior, fertility, gestation, parturition, and lactation in mammals and understanding the role of hormones in these processes is essential for species conservation. Sirenia is a unique order of marine mammals that include manatees, dugongs, and the extinct Steller's sea cow. Extant Sirenian species are all listed as vulnerable due to habitat loss, cold stress, boat strike trauma, harmful algal bloom toxicity, entanglements, and illegal hunting. Therefore, successful reproduction is essential to maintaining and increasing Sirenian populations. Understanding Sirenian reproductive behavior, endocrinology, and mating strategies will aid conservation and management efforts to protect and provide the proper conditions for successful reproduction. The objectives of this review were to synthesize the current knowledge regarding reproductive cycles and endocrinology of Sirenians and identify knowledge gaps for future investigation. The current literature on Sirenian reproductive physiology reports reproductive seasonality, sexual maturation, estrous cyclicity and acyclicity, pregnancy, and sex differences. However, there remain significant knowledge gaps on the cyclicity and pulsatile release of gonadotropins, maturation in females, and characterization of pregnancy hormone profiles throughout gestation. To date, there is no explanation for confirmed pattern for ovarian acyclicity, nor understanding of the function of the numerous accessory corpus luteum described in manatees. Research including a greater number of longitudinal and postmortem studies on a wider variety of wild manatee populations are important first steps. Taken together, understanding the reproductive endocrinology of these vulnerable and threatened species is critical for policy and management decisions to better inform protection initiatives.

Exposure to the reproductive endocrinology subspecialty among obstetrics and gynecology residency programs.

PURPOSE: Prior studies found that Ob-gyn trainees believe they have inadequate experience in the REI subspecialty. We evaluated the amount of time devoted to REI within the 4-year rotation schedule of ACGME-accredited Ob-gyn residency programs. METHODS: A list of current Ob-gyn residency programs, both with and without REI fellowships, was created using ACOG and ACGME databases. The programs' websites were reviewed, or the program coordinator was queried to determine the length and year of REI rotation, and the career or fellowships pursued by alumni. Wilcoxon rank sum test was utilized to assess differences in total REI rotation time between REI-affiliated and non-affiliated programs. Spearman's correlation was utilized to assess the association between total REI exposure and the percentage of alumni pursuing REI fellowships. RESULTS: Cumulative length of REI rotations throughout residency ranged from 0 to 20 weeks. Mean cumulative rotation length was greater in non-REI than in REI-affiliated programs (7.4 weeks vs. 6.1 weeks, p = 0.007). However, REI-affiliated programs had greater exposure to REI rotations during the first 2 years of residency (3.9 weeks vs 3.1 weeks, p = 0.042). Among all programs, 24% had the REI rotation in PGY-1, 61% in PGY-2, 50% in PGY-3, and 16% in PGY-4. The proportion of alumni matching in REI fellowship was significantly greater in REI-affiliated programs than non-REI affiliated programs (9.5% vs. 3.1%, p < 0.001). CONCLUSION: Compared to non-REI affiliated programs, Ob-gyn residencies affiliated with REI fellowships spend less time throughout residency training in REI rotations while sending a greater proportion of residents to REI fellowships.

Cause of fetal growth restriction during high-altitude pregnancy.

High-altitude pregnancy increases the incidence of fetal growth restriction and reduces birth weight. This poses a significant clinical challenge as both are linked to adverse health outcomes, including raised infant mortality and the development of the metabolic syndrome in later life. While this reduction in birth weight is mostly understood to be driven by the hypobaric hypoxia of high altitude, the causative mechanism is unclear. Moreover, it is now recognized that highland ancestry confers protection against this reduction in birth weight. Here, we analyze the evidence that pregnancy at high altitude reduces birth weight and that highland ancestry confers protection, discussing mechanisms contributing to both effects.

Ovulation provides excessive coagulation and hepatocyte growth factor signals to cause postoperative intraabdominal adhesions.

Postoperative adhesions show a higher occurrence in females aged 16-60, especially after pelvic surgeries. This study explores the role of ovulation in adhesion formation in mice. Ovarian surgery in mice with normal- or super-ovulation led to pronounced adhesions, whereas ovulation-defective Pgr-KO mice showed minimal adhesions. Specifically, exposure to ovulatory follicular fluid (FF) markedly increased the adhesion. The hazardous exposure time window was one day before to 2.5 days after the surgery. Mechanistically, early FF exposure triggered adhesions via the blood coagulation cascade, while later exposure relied on the HGF/cMET signaling pathway. Prophylactic administration of a thrombin inhibitor pre-operatively or a cMET inhibitor postoperatively effectively mitigated FF-induced adhesions, while COX inhibitor treatment exhibited no discernible effect. These findings underscore ovulation as a pivotal factor in the development of pelvic wound adhesions and advocate for targeted preventive strategies such as c-MET inhibition, scheduling surgeries outside the ovulatory period, or employing oral contraceptive measures.

Guideline for gynecological practice in Japan: Japan Society of Obstetrics and Gynecology and Japan Association of Obstetricians and Gynecologists 2023 edition.

Twelve years after the first edition of The Guideline for Gynecological Practice, which was jointly edited by The Japan Society of Obstetrics and Gynecology and The Japan Association of Obstetricians and Gynecologists, the 5th Revised Edition was published in 2023. The 2023 Guidelines includes 5 additional clinical questions (CQs), which brings the total to 103 CQ (12 on infectious disease, 30 on oncology and benign tumors, 29 on endocrinology and infertility and 32 on healthcare for women). Currently, a consensus has been reached on the Guidelines, and therefore, the objective of this report is to present the general policies regarding diagnostic and treatment methods used in standard gynecological outpatient care that are considered appropriate. At the end of each answer, the corresponding Recommendation Level (A, B, C) is indicated.

Endometriosis and endometrial cancer: A propensity score-adjusted real-world data study.

Endometriosis is a benign condition characterized by the presence of ectopic endometrial tissue. Our study investigated the effect of endometriosis on the risk of endometrial cancer (EC) and the prognosis of endometriosis-associated EC. In our study, 197,196 patients with endometriosis and without a previous diagnosis of EC were compared with 6,455,556 females encountering health services for examinations, with body mass index (BMI) data, and without endometriosis or EC. A propensity score generated 197,141 matched pairs. In the endometriosis cohort, 875 cases of EC were seen, whereas 558 were in the control group: the hazard ratio (HR) was 1.56 (95% CI 1.40-1.73, p < 0.001). Women with endometriosis were more likely to develop invasive endometrioid (p = 0.005) and clear cell (p < 0.001) EC. There was no difference in overall survival between endometriosis-associated EC and EC without endometriosis. Our epidemiological findings were consistent with the evidence of an association between endometriosis and EC.

Tannic acid alleviates 3-nitropropionic acid-induced ovarian damage in Brandt's vole (Lasiopodomys brandtii).

Tannic acid (TA) is a polyphenol with antioxidant properties present in various plants. In this study, we explored the protective effect of TA against ovarian oxidative stress in Brandt's voles and its underlying mechanism. At various doses, 3-nitropropionic acid (3-NPA) was intraperitoneally injected into Brandt's voles to simulate ovarian oxidative stress. Thereafter, various doses of TA were intragastrically administered to examine the protective effect of TA against 3-NPA-induced ovarian damage. Changes in inflammation, autophagy, apoptosis, and oxidative stress-related factors were investigated through various biochemical and histological techniques. Ovarian oxidative stress was successfully induced by the intraperitoneal administration of 12.5 mg/kg 3-NPA for 18 days. As a result, the ovarian coefficient decreased and ovarian tissue fibrosis was induced. TA treatment effectively alleviated the increase in luteinizing hormone and follicle-stimulating hormone levels; the decrease in estradiol, progesterone, and anti-Müllerian hormone levels; and the decline in fertility induced by 3-NPA. Compared to that in the 3-NPA group, TA decreased the expression of autophagy-related proteins beclin-1 and LC3, as well as the level of apoptosis. It also activated the AKT/mTOR signaling pathway, downregulated PTEN and p-NF-κB expression, and upregulated Nrf2 expression. In conclusion, our findings indicate that TA could inhibit autophagy via the regulation of AKT/mTOR signaling, suppressing oxidative damage and inflammatory responses through Nrf2 to alleviate 3-NPA-induced ovarian damage. Collectively, the current findings highlight the protective effects of TA in Brandt's vole, where it promotes the maintenance of normal ovarian function.

Standardized Reproductive Endocrinology and Infertility Consultation for Pediatric and Adolescent Oncology Patients.

Purpose: To investigate the role of formal reproductive endocrinology and infertility (REI) consultation in fertility preservation counseling in a pediatric/adolescent oncology patient population. Methods: Retrospective chart review was performed at an academic adult hospital from 2021 to 2022. Pre- and postpubertal patients admitted to the pediatric/adolescent oncology service with cancer diagnoses and imminent gonadotoxic chemotherapy plans were included. Baseline characteristics were collected, including patient age, sex, race, language, insurance, and cancer diagnosis. Primary outcomes were formal REI consultation and fertility preservation election. Results: Nineteen of 58 eligible patients received a formal REI consultation. Patients were more likely to elect fertility preservation if they received a consult. Females were more likely to receive a consult than males and more likely to elect fertility preservation. Patients of age ≥16 years were more likely to receive consultation than younger patients. However, all patients of age <16 years who received a consult elected fertility preservation. There was no difference in consultation based on race, language, or insurance. Thirteen of 19 patients who received an REI consultation elected fertility preservation. Ten of 11 female elections were ovarian suppression, an unproven method of fertility preservation. The two male elections were semen cryopreservation. Conclusion: Underutilization of formal REI consults and a relative lack of proven fertility preservation elections may shed light on a need for increased fertility preservation awareness among young oncology patients and the providers who care for them. A streamlined process that automates formal REI consultation for all eligible patients may maximize the potential for comprehensive counseling and improve patient participation in fertility preservation.

Improved Screening for Depression in Patients Initiating Fertility Treatment.

OBJECTIVE: To improve screening for depression in patients who are initiating fertility treatment at a reproductive endocrinology and infertility (REI) center by screening all patients at their initial visit using the Patient Health Questionnaire-9 (PHQ-9). DESIGN: This quality improvement project was conducted using a plan-do-study-act cycle implemented with a postintervention study design. SETTING/LOCAL PROBLEM: A medium-size REI center in a mid-Atlantic U.S. metropolitan area where screening for mental health status in patients initiating fertility treatments was not occurring. PARTICIPANTS: Patients who were scheduled in person with REI providers for a new patient consult regarding fertility were declared eligible. INTERVENTION/MEASUREMENTS: The PHQ-9 was administered by providers at initial consults for patients seeking fertility treatments from October 2022 to February 2023. Three cycles of the plan-do-study-act model were used to execute change. For all patients who scored 5 to 9 (mild depression), conversations regarding counseling referrals occurred. For all patients who scored ≥10 (moderate to severe depression), a referral for counseling and medication management was generated. Data were analyzed via descriptive statistics. RESULTS: A total of 115 participants were included. A screening rate of 84.3% (n = 97) was achieved for patients initiating treatment. Of the 97 screened, 21 patients had a score of ≥5; 19 were given a referral for counseling. However, none of the patients attended a counseling session or started medication prescribed by their primary care provider during the 2-month follow-up period. Barriers identified included costs, personal preferences, and access to services. CONCLUSION: The PHQ-9 screening tool was implemented at an REI clinic to improve the frequency of mental health screenings and provide necessary referrals. However, additional follow-up is needed to ensure patients are receiving appropriate mental health care.

An overview and comprehensive analysis of interdisciplinary clinical research in endometriosis based on trial registry.

Endometriosis is a chronic multisystem disease associated with immunological, genetic, hormonal, psychological, and neuroscientific factors, leading to a significant socioeconomic impact worldwide. Though multidisciplinary management is the ideal approach, there remains a scarcity of published interdisciplinary clinical trials at present. Here, we have conducted a comprehensive analysis of the characteristics and issues of interdisciplinary trials on endometriosis based on the clinical registration database ClinicalTrials.gov. Among all 387 endometriosis trials, 30% (116) were identified as interdisciplinary, mostly conducted in Europe and North America, and fully funded by non-industrial sources. We documented growth in both patient-centered multidisciplinary comprehensive management and collaboration between fundamental biomedical science and applied medicine. However, compared to traditional obstetric-gynecological trials, interdisciplinary studies exhibited negative characteristics such as less likely to be randomized and less likely to report results. Our study provides insights for future trial investigators and may contribute to fostering greater collaboration in medical research.

High paternal homocysteine causes ventricular septal defects in mouse offspring.

Maternal hyperhomocysteinemia is widely considered as an independent risk of congenital heart disease (CHD). However, whether high paternal homocysteine causes CHD remains unknown. Here, we showed that increased homocysteine levels of male mice caused decreased sperm count, sperm motility defect and ventricular septal defect of the offspring. Moreover, high levels of paternal homocysteine decrease sperm DNMT3A/3B, accompanied with changes in DNA methylation levels in the promoter regions of CHD-related genes. Folic acid supplement could decrease the occurrence of VSD in high homocysteine male mice. This study reveals that increased paternal homocysteine level increases VSD risk in the offspring, indicating that decreasing paternal homocysteine may be an intervening target of CHD.

KLF2 controls proliferation and apoptosis of human spermatogonial stem cells via targeting GJA1.

Human spermatogonial stem cells (SSCs) are essential for spermatogenesis and male fertility. However, molecular mechanisms regulating fate determinations of human SSCs remain elusive. In this study, we revealed that KLF2 decreased the proliferation, DNA synthesis, and colonization of human SSCs as well as increased apoptosis of these cells. We identified and demonstrated that GJA1 was a target gene for KLF2 in human SSCs. Notably, KLF2 overexpression rescued the reduction of proliferation of human SSCs caused by GJA1 silencing as well as the enhancement of apoptosis of human SSCs. Abnormalities in the higher level of KLF2 and/or KIF2 mutations might lead to male infertility. Collectively, these results implicate that KLF2 inhibits proliferation of human SSCs and enhances their apoptosis by targeting GJA1. This study thus provides novel genetic mechanisms underlying human spermatogenesis and azoospermia, and it offers new endogenous targets for treating male infertility.

Tilapia, a good model for studying reproductive endocrinology.

The Nile tilapia (Oreochromis niloticus), with a system of XX/XY sex determination, is a worldwide farmed fish with a shorter sexual maturation time than that of most cultured fish. Tilapia show a spawning cycle of approximately 14 days and can be artificially propagated in the laboratory all year round to obtain genetically all female (XX) and all male (XY) fry. Its genome sequence has been opened, and a perfect gene editing platform has been established. With a moderate body size, it is convenient for taking enough blood to measure hormone level. In recent years, using tilapia as animal model, we have confirmed that estrogen is crucial for female development because 1) mutation of star2, cyp17a1 or cyp19a1a (encoding aromatase, the key enzyme for estrogen synthesis) results in sex reversal (SR) due to estrogen deficiency in XX tilapia, while mutation of star1, cyp11a1, cyp17a2, cyp19a1b or cyp11c1 affects fertility due to abnormal androgen, cortisol and DHP levels in XY tilapia; 2) when the estrogen receptors (esr2a/esr2b) are mutated, the sex is reversed from female to male, while when the androgen receptors are mutated, the sex cannot be reversed; 3) the differentiated ovary can be transdifferentiated into functional testis by inhibition of estrogen synthesis, and the differentiated testis can be transdifferentiated into ovary by simultaneous addition of exogenous estrogen and androgen synthase inhibitor; 4) loss of male pathway genes amhy, dmrt1, gsdf causes SR with upregulation of cyp19a1a in XY tilapia. Disruption of estrogen synthesis rescues the male to female SR of amhy and gsdf but not dmrt1 mutants; 5) mutation of female pathway genes foxl2 and sf-1 causes SR with downregulation of cyp19a1a in XX tilapia; 6) the germ cell SR of foxl3 mutants fails to be rescued by estrogen treatment, indicating that estrogen determines female germ cell fate through foxl3. This review also summarized the effects of deficiency of other steroid hormones, such as androgen, DHP and cortisol, on fish reproduction. Overall, these studies demonstrate that tilapia is an excellent animal model for studying reproductive endocrinology of fish.

Subspecialty Faculty in Obstetrics and Gynecology: Distribution, Demographics, and Implications for Training and Clinical Practice.

OBJECTIVE: The objective of this study was to quantify the subspecialist workforce involved in the clinical education of Obstetrics and Gynecology (OBGYN) residents and to provide an overview of the subspecialist faculty workforce geographic distribution and demographics. METHODS: This cross-sectional, observational study used public data collected from July 1, 2022, through August 31, 2022. A list of Obstetrics and Gynecology residency programs, their sponsoring institutions/locations, and affiliated locations was compiled from the American Medical Association's Fellowship and Residency Electronic Interactive Database. Faculty subspecialists' names were collected by manually searching each program's website. Demographics were collected from the National Plan and Provider Enumeration System. Subspecialty faculty who had completed an Obstetrics and Gynecology residency, were fellowship trained, and/or had board certification in the subspecialty were included in the study. RESULTS: A total of 4,659 subspecialist faculty were identified from 278 residency programs, representing 81.5% of the total subspecialist workforce in Obstetrics and Gynecology (n=5,716). Of the subspecialists identified, 2,838 were faculty at sponsoring institutions, representing 49.7% of the entire subspecialist workforce; the remainder worked with residents at affiliate locations. Our results showed 59.9% of subspecialists were female and 40.1% were male; 97.0% were allopathic subspecialists. The largest proportion of subspecialists were in the age group of 40-49 years (36.6%). Subspecialists were present in 45 states, with the exception of Alaska, Idaho, Montana, North Dakota, South Dakota, and Wyoming. CONCLUSION: Most of the Obstetrics and Gynecology subspecialty workforce is involved in the clinical education of OBGYN residents, with half of the workforce on faculty at the residency program sponsor site. The subspecialty faculty workforce is primarily female, has an allopathic degree, is mid-career, and is geographically diverse.

Strengthening the Reproductive Endocrinology and Infertility Curriculum Through Three Interactive Cases.

Introduction: Improved reproductive endocrinology and infertility (REI) curricula are needed to address educational deficiencies both at our institution and on a national level. To improve REI education for OB/GYN residents and medical students, we developed and piloted a curriculum with in-person and virtual flexibility. Methods: We developed three clinical vignettes for a facilitator-led case-based discussion among OB/GYN residents: two office cases and one emergency scenario. Cases were evaluated by content experts and tested before implementation. Pre- and postsurveys included both multiple-choice questions on content and a Likert-scale self-assessment of comfort, satisfaction, and knowledge. Postsurveys were administered immediately postintervention and at a delayed interval. Responses were compared using paired t tests and McNemar tests. Results: Eighteen learners (16 OB/GYN residents and two medical students) participated, the majority in person, of whom 17 (94%) completed a postsurvey. Self-rated proficiency in evaluating and managing irregular menses, infertility, and amenorrhea all improved significantly immediately following the intervention (p < .05 for all). Learners reported significantly more knowledge and comfort with REI compared to other subspecialties following the intervention (p < .05). More learners responded correctly to knowledge questions postintervention (p < .05 for questions 1 and 2, p = .16 for question 3). All learners were satisfied with and enjoyed the curriculum. Eight learners completed the delayed postsurvey and showed sustained improvements in knowledge and competence with REI content. Discussion: Facilitator-guided case-based learning was effective in improving learners' confidence, comfort, and knowledge in managing REI conditions, and improvements were sustained following a delayed interval.

Increased Serum Levels of Phoenixin-14, Nesfatin-1 and Dopamine Are Associated with Positive Pregnancy Rate after Ovarian Stimulation.

BACKGROUND: We study the relationship between phoenixin (PNX-14), nesfatin-1 (NES-1), dopamine (DA) and oxytocin (OT) levels together with pregnancy rates in women after ovarian stimulation (OS). METHODS: In a prospective case-control study, 56 infertile women were enrolled from the Department of Gynecological Endocrinology University Hospital. Infertile women age < 40 years old, with polycystic ovary syndrome (PCOS), confirmed tubal patency and suitable sperm quality were included. Blood samples were drawn twice-before the initiation of OS and before the human chorionic gonadotropin (hCG) administration. Assessments of PNX-14, NES-1, DA and OT serum levels were performed. Pregnancy rates after OS were observed. RESULTS: Pregnant women showed higher baseline NES-1 and OT levels (+29.2% and +44%) but not PNX-14 and DA levels when compared to non-pregnant ones. In pregnant women, positive correlations between OT and prolactin, PRL (r = 0.47, p = 0.04), as well as between OT and NES-1 (r = 0.55, p = 0.02), were observed at baseline. At baseline, an OT level increase was associated with a positive pregnancy rate (per 100 pg/mL, OR = 1.39, 95% CI 1.04-1.74), while after OS, higher PNX-14 was a predictor of pregnancy (by 10 pg/mL, OR = 1.23, 95%CI 1.07-1.39). Post-stimulation PNX-14, NES-1 and DA concentrations were higher in pregnant women compared to non-pregnant ones (+17.4%, +26.1%, and +45.5%, respectively; all p < 0.05). In the pregnant group, OT levels were 2.7-times lower than in the remainder (p = 0.03). Moreover, in pregnant participants, a negative association between NES-1 and PNX (r = -0.53, p = 0.024) was observed. CONCLUSION: Elevated PNX-14, NES-1 and DA along with decreased OT levels were observed in women who achieved pregnancy.

Gonacin: A germ cell-derived hormone with glucogenic, orexigenic, and gonadal activities.

Fish require abundant nutrients to generate a large number of eggs for spawning. Based on the evolutionary conservation of human FBN2 and its C-terminal placensin-like sequences in fish, we identified a peptide hormone gonacin (GONAdal Cell placensIN) and found its high expression in early-stage germ cells in the ovary and testis of zebrafish. We demonstrated that gonacin is essential for food intake, glucose release, and ovarian development in zebrafish. Similar expression patterns and functions of gonacin were also demonstrated in rainbow trout. Gonacin represents the first hormone secreted by germ cells with endocrine functions in vertebrates, bridging the energy homeostasis and reproduction.