General Background: Hormonal contraception is widely used, yet its implications for ovarian reserve markers remain debated. Specific Background: Cross-sectional studies report lower anti-Müllerian hormone (AMH) and antral follicle count (AFC) among users, but lack baseline data to determine temporal dynamics and reversibility. Knowledge Gap: Prospective evidence with serial baseline and follow-up measures comparing contraceptive methods is limited. Aims: This study prospectively evaluated longitudinal changes in AMH, AFC, and follicle-stimulating hormone among women initiating combined oral contraceptives or levonorgestrel-releasing intrauterine devices versus non-users. Results: Mixed-effects models demonstrated significant time-by-group interactions, with early declines in AMH and AFC at three months, followed by partial recovery during continued use, while controls remained stable. Novelty: By integrating baseline and repeated measures, this study delineates functional, time-dependent suppression rather than structural ovarian damage. Implications: Findings support counseling that hormonal contraception induces temporary, reversible alterations in ovarian reserve markers and should not be interpreted as permanent fertility impairment.Keywords : Hormonal Contraception, Anti-Müllerian Hormone, Ovarian Reserve Markers, Longitudinal Cohort Study, Oral ContraceptivesHighlight : AMH levels decreased 25-29% at 3 months, then partially recovered by 12 months Changes reflect temporary ovarian suppression, not permanent structural damage to ovaries Both OCP and LNG-IUD users showed similar suppression and recovery patterns

Premature ovarian insufficiency (POI) is a fertility disorder impacting women under 40, characterized by an early deterioration of ovarian function, and is one of the major side effects caused by chemotherapy. Cyclophosphamide is a powerful chemotherapeutic agent used in various cancers; however, it inflicts substantial harm on other tissues, particularly the gonads, leading to temporary or permanent infertility. Forty female albino rats (Rattus norvegicus) were divided into four groups. Group I (control group) received normal saline, then premature ovarian insufficiency was induced in the remaining groups by intraperitoneal injections of cyclophosphamide (CLP). After that, Group II received no treatment. Group III was administered a daily oral dose of pomegranate (Punica granatum) nanoparticles for one month. Group IV received a daily oral dose of pomegranates, as did group III, plus ovarian stem cell-derived exosomes via intraperitoneal injection twice weekly for one month. Rats were euthanized 30 days post-POI induction; blood was then collected to evaluate hormone levels, and sections of the ovaries were collected for histopathological analysis. Frozen sections were procured for gene expression and oxidative stress studies. The hormonal assessment of groups indicated a notable reduction in estrogen (E2) level and an elevation of follicle-stimulating hormone (FSH) in group II compared to the control and treated groups. Additionally, the ovaries of group II exhibited pronounced degeneration of ovarian follicles, accompanied by the desquamation of granulosa cells. Gene expression study indicated a downregulation of FSHR, CYP19A1, and AMH in the same group. Rats in both groups III and IV exhibited an increased number of follicles, improved ovarian shape, a considerable elevation in blood E2, a marked decrease in serum FSH levels, and an up-regulation of the three examined genes. The study aimed to assess the therapeutic efficacy of pomegranate (Punica granatum) peel extract nanoparticles alone and their synergistic effect with ovarian stem cell exosomes in reversing premature ovarian insufficiency (POI) caused by cyclophosphamide. Treatment with (Punica granatum) nanoparticles and exosomes partially enhanced the structure and function of the ovaries, thereby alleviating the adverse effects of Cyclophosphamide.

Prenatal PFHxS Exposure Alters Ovarian Development in Female Adolescent Mice: Transcriptomic, Hormonal, and Structural Evidence of Disrupted Steroidogenesis.

Objective This study aimed to assess the therapeutic potential of Yangjing Shugan decoction (YJSGD) in D-galactose (D-gal)-induced Premature Ovarian Failure (POF) mice and to elucidate its underlying mechanisms. Methods The main metabolites in YJSGD were characterized. A D-gal-induced POF mouse model was established and intervened with YJSGD at doses of 25, 50, and 100 mg/kg. A comprehensive analysis encompassing ovarian function, oxidative stress, inflammation, the Sirt1/Nrf2 pathway, gut microbiota, short-chain fatty acids (SCFAs), and serum metabolomics was conducted. Results The results demonstrated that YJSGD effectively restored estrous cyclicity, normalized serum estradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels, and improved ovarian follicular development. YJSGD treatment also enhanced systemic antioxidant capacity and attenuated inflammation. Mechanistically, the therapeutic effects were associated with the upregulation of the Sirt1/Nrf2 signaling pathway in the ovary, as evidenced by increased protein expression of Sirt1, Nrf2, and HO-1, and suppressed Keap1. Furthermore, YJSGD ameliorated gut microbiota dysbiosis, promoted beneficial SCFAs production, and rectified serum metabolic disturbances involved in amino acid, lipid, and energy metabolism. Conclusion The results indicate that YJSGD is a promising multi-target agent for POF treatment, and its synergistic effects on reproductive, oxidative, and gut microbiota homeostasis provide a solid basis for its clinical application.

A key objective of the dairy industry is to balance genetic progress with reproductive efficiency. Ovum pick-up followed by in vitro embryo production (OPU-IVP) is a pivotal technology for accelerating genetic gain. However, the relationship between follicle size and oocyte developmental competence in high-producing dairy cows under hormonal stimulation remains to be fully elucidated. This study systematically evaluated the effects of follicle diameter ovum pick-up on OPU-IVP outcomes and the underlying follicular fluid (FF) microenvironment. A total of 109 high-yielding Holstein cows were subjected to ovarian stimulation and OPU. Follicles were categorized as small (2.0–5.9 mm), medium (6.0–9.9 mm), or large (10.0–20.0 mm). Oocyte recovery, quality, and developmental competence were assessed. FF was analyzed for hormonal profiles, including anti-Müllerian hormone (AMH), estradiol (E2), follicle-stimulating hormone (FSH), and progesterone (PROG); oxidative stress markers, including malondialdehyde (MDA), glutathione peroxidase (GPx), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC); and untargeted metabolomics (n = 10 per group). Consistently, oocytes from medium follicles exhibited superior developmental competence, achieving the highest maturation (89.93%), cleavage (72.19%), and blastocyst rates (41.88%). In contrast, large follicles had a low recovery rate (32.64%), a high proportion of degenerated oocytes (32.00%), and reduced embryonic efficiency. Metabolomic profiling revealed distinct microenvironmental differences, with medium follicles enriched in pathways like pyruvate metabolism and arachidonic acid metabolism indicating an optimal metabolic state. Hormonally, AMH decreased while E2 and PROG increased with follicle size. Large follicles exhibited significantly elevated MDA levels, indicating oxidative stress, without a concurrent rise in antioxidant capacity. In conclusion, while small follicles provide an abundant source of morphologically good oocytes, medium follicles (6.0–9.9 mm) represent a distinct “window of competence” for OPU-IVP, characterized by a follicular microenvironment most conducive to embryo production. Excessive reliance on large follicle aspiration should be avoided due to signs of over-maturity and oxidative damage. These findings provide a physiological basis for optimizing OPU strategies to enhance IVP efficiency in high-producing dairy cows.

Gonadotropin-releasing hormone (GnRH) tightly regulates the synthesis and the release of gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), while the intracellular molecular mechanisms following GnRH signal for the regulation of transcription remains incompletely understood. In this study, we used primary culture of rat anterior pituitary cells to investigate the role of NR4A transcription factors (NR4A1, NR4A2, and NR4A3) in GnRH regulation of gonadotropin secretion. GnRH agonist stimulation rapidly and transiently increased Nr4a1, Nr4a2, and Nr4a3 expression within one hour, accompanied by a time-dependent increase in Fshb mRNA levels and the secretion of both FSH and LH. The knockdown of each Nr4a gene using siRNA significantly reduced Fshb expression under GnRH stimulation. Nr4a1 knockdown caused the most pronounced decrease in FSH secretion. Although Lhb and Cga mRNA levels were largely unaffected, LH secretion was consistently reduced following NR4A knockdown. These findings suggest that NR4A transcription factors act downstream of GnRH signaling to promote Fshb transcription and facilitate gonadotropin secretion, thereby modulating GnRH-dependent control of FSH and LH secretion.

Follicle-stimulating hormone (FSH) coordinates ovarian follicle development by aligning mitochondrial biogenesis with increased metabolic demand. Although FSH is known to stimulate glycolysis in granulosa cells (GCs), the mechanism by which glycolytic flux coupled to mitochondrial biogenesis remains unclear. Here, we demonstrate that histone lactylation functions as a lactate-sensitive epigenetic mediator linking FSH-driven metabolic alterations to mitochondrial biogenesis in GCs. Mechanistically, FSH increases intracellular lactate levels through glycolytic activation, thereby promoting P300/CBP-dependent lactylation of histone H4 at lysine 5 (H4K5la). H4K5la directly enhances HDAC4 expression, and HDAC4 subsequently deacetylates PGC-1α at lysine residues 329/330. Deacetylated PGC-1α cooperates with nuclear respiratory factors NRF1/2 to drive transcription of key mitochondrial regulators (TFAM, TFB1M, TFB2M), ultimately promoting mitochondrial biogenesis. Disruption of the H4K5la/HDAC4/PGC-1α axis markedly impaired mitochondrial biogenesis and follicular development, evidenced by reduced ovarian weight, smaller follicle size, decreased antral follicle number, and impaired GC proliferation and estradiol (E2) production in FSH-treated mice. These findings identify a metabolic–epigenetic regulatory pathway in which histone lactylation links glycolysis to mitochondrial adaptation, providing mechanistic insight into FSH-dependent reproductive physiology.

Nonfunctioning pituitary adenomas (NFPAs) have historically been characterized histologically based on hormonal immunostaining. The 2017 World Health Organization guidelines for pituitary neuroendocrine tumors further delineated NFPA classification based on biologically relevant transcription factors (TFs), including T-PIT, PIT-1, and steroidogenic factor 1 (SF-1). We sought to evaluate differences in NFPA immunohistochemistry (IHC) associated with biological sex and age according to new TF immunostaining criteria. A retrospective review of data from a single institution was conducted to identify patients who had undergone NFPA resection from 2012 to 2023. Patients grouped based on their biological sex and then further divided into age categories. Univariable statistics were used to identify associations between patient demographics and NFPA IHC. A total of 416 patients were included in the IHC-hormone analysis, and 154 patients were included in the IHC-TF analysis. Men were significantly less likely to have NFPAs with positive immunostaining for T-PIT (odds ratio [OR] = 0.15, 95% CI: 0.06-0.37) or adrenocorticotropic hormone (OR = 0.38, 95% CI: 0.22-0.64) and significantly more likely to have NFPAs stain positive for SF-1 (OR = 4.87, 95% CI: 2.24-10.6), follicle-stimulating hormone (FSH) (OR = 2.46, 95% CI: 1.64-3.69), luteinizing hormone (OR = 2.28, 95% CI: 1.26-4.13), thyroid-stimulating hormone (OR = 2.56, 95% CI: 1.05-6.26), or the alpha subunit (OR = 2.01, 95% CI: 1.36-2.97). Compared with the youngest age group, women in the oldest age group were more likely to have an NFPA stain positive for SF-1 (OR = 6.88, 95% CI: 1.86-25.4), FSH (OR = 2.32, 95% CI: 1.02-5.27), or the alpha subunit (OR = 2.14, 95% CI: 1.02-4.47). Similarly, men in the oldest age group were more likely to have an NFPA staining positive for FSH (OR = 4.16, 95% CI: 1.90-9.11) and the alpha subunit (OR = 2.36, 95% CI: 1.10-5.05); they were less likely to have positive immunostaining for adrenocorticotropic hormone (OR = 0.19, 95% CI: 0.04-0.79). There were no age-related differences in TF staining for male patients. This study demonstrates that sex and age are important demographic factors associated with immunostaining patterns and TF lineage subtypes for NFPAs. Underlying endocrine factors dictated by age and sex may represent a role in tumorigenesis or progression of NFPAs.

Klinefelter Syndrome (KS) is a genetic disorder which affects 1 out of every 600 males in the United States. Previous studies indicate KS has significant differences in areas such as quality of life, testicular function, and learning, although little research exists to explain the neurodevelopmental implications. The purpose of this literature review was to synthesize existing literature on KS, which was primarily categorized into the impacts on memory, brain volume and activation, and endocrine function. Research focusing on the neurodevelopmental implications of KS were selected, with a preference for studies which performed statistical analysis through an observational or experimental design. Articles were collected from a multitude of countries. Across the existing literature, KS has been shown to produce significant impairments on working memory and explicit memory, with negative neurodevelopmental impacts. KS exhibits reduced gray matter in the brain and limited activation in areas crucial for processes such as learning. In terms of endocrine function, KS produces reduced levels of testosterone, halting growth in parts of the brain essential to neurodevelopment. It has also increased the prevalence of Follicle Stimulating Hormone (FSH) resulting in numerous mental health disorders. Limitations include a lack of statistical significance in some studies, uniformity across multiple countries and research groups, and small sample sizes. Future research must address these concerns and foster collaboration between different specialists in the field of KS. These actions are imperative to improving early diagnosis of KS and create effective intervention strategies, improving quality of life for KS men and their families.

What are the outcomes for prepubertal and pubertal girls with Turner syndrome (TS) in terms of fertility counselling and preservation? Fertility counselling is crucial for prepubertal and pubertal girls with TS, as it can facilitate their pursuit of fertility preservation (FP), primarily through oocyte cryopreservation (OC) and is particularly relevant for patients with blood karyotype abnormality with good prognosis for future fertility. TS is a common genetic condition affecting ∼1 in 2500 live-born girls. One consequence of TS is premature ovarian insufficiency, significantly impacting the quality of life in adulthood. Therefore, appropriate counselling and effective FP or solutions are essential. When OC is proposed, the role of anti-Müllerian hormone (AMH) and FSH in predicting the outcomes of OC has been examined in the literature with controversial data. This retrospective observational study was conducted at the Reproductive Biology Laboratory-CECOS of Rouen University Hospital, evaluating the follow-up of 40 prepubertal and pubertal girls with TS referred for fertility counselling. Clinical and biological data were collected from medical records between January 2008 and December 2022. Prepubertal and pubertal patients with TS attended a fertility counselling consultation, accompanied by their parents or legal guardian if they were under the age of 18years. The impact of TS on future fertility and potential FP procedures, including OC, were explained. An assessment of ovarian reserve was conducted. Based on the results and depending on the patient's pubertal status, FP could be initiated immediately in TS patients with spontaneous menarche or follow-up could continue until spontaneous puberty and menarche occur. In terms of FP, 25% (10/40) of the patients underwent OC. On average, 4.9 ± 3.8 oocytes per controlled ovarian hyperstimulation cycle were cryopreserved. No relationship was found between basal FSH or AMH serum level, karyotype abnormalities, and the number of mature oocytes retrieved. Conversely, a positive correlation was observed between the peak estradiol level at the time of triggering and the number of mature oocytes retrieved. In the multiple linear regression analysis with cross-validation, the peak estradiol level at triggering remained the only variable independently associated with mature oocyte yield. Most patients were aware of the impact of TS on future fertility but were uninformed about available parenthood alternatives. The number of TS patients included in our study is a limitation, as well as the monocentric and retrospective nature of the study. Therefore, our data should be interpreted with caution. Fertility counselling and FP are essential for prepubertal and pubertal TS patients. Regular and systematic follow-up of ovarian reserve and function should be implemented in their medical care. OC is a feasible option for some TS patients and should be considered after menarche but delayed until further pubertal maturation to allow robust patient engagement in the decision-making process. Further studies are needed to evaluate factors influencing the number of mature oocytes retrieved and the optimal number of oocytes necessary to ensure a good chance of pregnancy. This work had institutional financial support from Rouen University Hospital. The authors have no conflicts of interest to declare. N/A.

Differential effects of follicle-stimulating hormone dosage on in vitro embryo production in high- and low-anti-Müllerian hormone Holstein heifers.

IntroductionPituitary apoplexy (PA) is an acute, potentially fatal clinical syndrome resulting from hemorrhage and/or infarction of the pituitary gland, which may require emergency surgery in some cases.The most common clinical complaint is severe headache, often accompanied by nausea, vomiting, visual disturbances, and altered consciousness. Life-threatening hypotension may also occur due to involvement of the anterior pituitary gland. Non-functioning pituitary adenomas (NFPA), specifically macroadenomas, appear to have the higher risk of apoplexy. We present a case of pituitary apoplexy presenting with nausea and vomiting following severe headache.Clinical CaseA 77-year-old male patient presented to an external center with complaints of severe headache, nausea, vomiting, hypotension, and decreased vision for 15 days and was referred to us with a preliminary diagnosis of panhypopituitarism. In his medical history, it was learned that he had been followed up for 13 years due to non-functioning pituitary macroadenoma and that he was examined for a hypertensive attack one week ago and started on olmesartan + hydrochlorothiazide combination therapy. Laboratory tests were as in Table 1. Prednisolone 4*20 mg/day was started due to secondary adrenal insufficiency. Contrast-enhanced pituitary MRI revealed a 14x17x20 mm, hemorrhagic, non-enhancing macroadenoma mass that expanded the sella, extended into the bilateral cavernous sinuses and suprasellar cisterns (Knosp grade I), and compressed the optic chiasm. This was interpreted as apoplexy secondary to hemorrhage (Figure 1). Visual field evaluation revealed bitemporal hemianopsia and optic disc effacement on the left side. Since these changes were evaluated as signs of chronic compression and the patient benefited from steroid treatment, emergency surgical intervention was not considered by the neurosurgeon. Due to the development of central hypothyroidism during follow-up, levothyroxine sodium 1*25 mcg was added to the treatment and the patient was discharged with prednisolone 8 mg/day by decreasing the steroid treatment.ConclusionNo large case series have been reported on the development of PA in the elderly. In this patient group, the frequent presence of comorbidities such as hypertension or diabetes, as in our case, increases the risk of PA. PA development is more common in non-functioning macroadenomas than in microadenomas. An ideal treatment approach for pituitary apoplexy has not been established. While urgent decompression may be necessary in patients with progressive visual field defects and deteriorating consciousness, conservative treatment is also an option in selected patients. It is important to note that the degree of symptoms at presentation and the clinical course of PA vary considerably among patients.Figure 1:Contrast-enhanced pituitary MRIA 14x17x20 mm, hemorrhagic, non-enhancing macroadenoma mass that expanded the sella, extended into the bilateral cavernous sinuses and suprasellar cisterns (Knosp grade I), and compressed the optic chiasm Table 1:Laboratory workup*ACTH:Adrenocorticotropic hormone, TSH: Thyroid Stimulating Hormone, FSH:Follicle stimulating hormone, LH: Luteinizing hormone, IGF-1: Insulin-like growth factor-1

IntroductionPituitary metastasis from a solid tumour is an extremely rare condition and is generally associated with a poor prognosis. Spontaneous regression is not typically expected, which further worsens the outlook. Here, we present a case of a patient with small-cell lung cancer (SCLC) who developed a pituitary mass. The marked regression of the lesion following chemotherapy strongly supported the likelihood of pituitary metastasis in this case.Clinical CaseA 59-year-old female patient, diagnosed with SCLC one month ago, was receiving radiotherapy and she also had a chemotherapy plan. When visual impairment and ptosis developed, cranial MRI was performed. She was referred to our outpatient clinic due to pituitary lesion. On physical examination blood pressure was 130/70 mmHg and a heart rate was 92/min. She was mildly dyspneic, had no signs of endocrine hyperfunction, nor polyuria or polydipsia. Obesity was also noted. Her medical history included hypertension and ischemic heart disease. In laboratory examination;ParameterResultReference RangeNa⁺140 mmol/L135–145 mmol/LK⁺4.9 mmol/L3.5–5.0 mmol/LBasal Cortisol30.3 μg/dL6.2–19.4 μg/dLACTH164 ng/L7.2–63.3 ng/LIGF-1471 μg/L62–186 μg/LTSH1.52 mIU/L0.27–4.8 mIU/LfT41.26 ng/dL0.79–1.59 ng/dLFSH9.6 IU/L3.5–12.6 IU/LLH4.08 IU/L2.4–12.6 IU/LProlactin20.3 μg/L2.8–29.2 μg/L1 mg Dexamethasone Suppression Test (DST)15.7 μg/dL—4 mg Dexamethasone Suppression Test (DST)18 μg/dL—Liver and Renal FunctionsNormal—Pituitary MRI revealed a 17×15×12 mm suprasellar mass lesion compressing the optic chiasm (Figure 1A-B). PET-CT demonstrated intense FDG uptake in the pituitary region, as well as involvement in the right lung’s lower, middle, and upper lobes, the left adrenal gland, and multiple lesions in the skeletal system. The patient was evaluated by a multidisciplinary pituitary board, and no clinical signs of acromegaly or Cushing’s syndrome were identified. Due to the high surgical risk given her condition, chemotherapy was promptly planned. Cisplatin and etoposide chemotherapy protocol was started, and the patient's visual impairment subsided following treatment. At the 3-month follow-up her visual complaints and ptosis completely resolved, basal cortisol decreased to 20 μg/dL, ACTH to 60 ng/L, and IGF-1 normalized. Control pituitary MRI releaved significant regression of the lesion (Figure 1C-D). In the first year of chemotherapy, during the pulmonology and oncology follow-up, she was hospitalized because of confusion following radiotherapy for brain metastases. It was later reported that the patient had passed away.ConclusionThe approach to pituitary metastases is generally palliative. On the other hand, if the primary tumor is expected to respond well to chemotherapy and surgery is considered high-risk, close monitoring may be considered to allow chemotherapy to be effective.Figure 1:A-B: Sagittal and coronal pituitary MRI images of the patient before chemotherapy. C-D: Sagittal and coronal pituitary MRI images of the patient 3 months after chemotherapy. Table 1:The patienteGFR: Estimated glomerular filtration rate, ACTH: Adrenocorticotropic hormone, IGF-1: Insulin-like growth factor 1, TSH: Thyroid stimulating hormone, fT4: Free thyroxine, FSH: Follicle-stimulating hormone, LH: Luteinizing hormone, E2: Estradiol, DST: Dexamethasone suppression test

Objective We aimed to analyze the correlation between the neutrophil-to-lymphocyte ratio (NLR), and the treatment outcomes for infertile women after in vitro fertilization (IVF) using embryo transfer technology. Methods This retrospective study enrolled women with infertility at Huzhou Maternal and Child Health Care Hospital who underwent in vitro IVF procedures. Patient data were collected from a reproductive electronic medical record system. We divided 976 participants into positive and negative groups based on embryo availability after IVF. Age, education level, body mass index, infertility type, etiology, miscarriage history, ovarian stimulation protocols, baseline follicle stimulating hormone levels, anti-Müllerian hormone and NLR were compared in both groups. We investigated the association between NLR and IVF outcomes using logistic regression analysis with multi-model adjustments. The receiver operating characteristic (ROC) curve was used to evaluate the screening efficacy of NLR, The subgroup analysis revealed risk variations among different groups. Finally, we performed sensitivity analysis by modifying control values and conducting logistic regression using NLR quartiles. Results Multimodal adjusted logistic regression analysis revealed a significant association between the second quartile of NLR and negative outcomes of IVF treatment, with an OR value and 95% confidence interval of 0.28 (0.10-0.67). The area under the ROC curve was 0.850 <. We observed an interaction between NLR quartiles and infertility types, particularly positive correlations between primary infertility, female-specific infertility factors, and no history of miscarriage with IVF outcomes at the second quartile. When the second quartile was adjusted as a reference value, the three remaining quartiles exhibited statistically significant differences compared to the second quartile ( p for trend = 0.045). Conclusion We recommended dynamically monitoring NLR during the cycle of ovulation induction and advocating individualized inflammatory management based on the cause of infertility to ensure the effectiveness of IVF treatment and prevent resource wastage.

Leuprorelin-induced perimenopausal syndrome (LIPS) represents a common challenge faced by infertile women undergoing assisted reproductive procedures, characterized primarily by hot flashes, night sweats, and mood swings. Currently, there is a shortage of safe approaches that can effectively alleviate these symptoms without compromising the therapeutic outcomes of pregnancy. In this study, 100 infertile women with LIPS (placebo group, MP group; probiotic group, ML group) and 50 healthy women were enrolled to evaluate the therapeutic effects of Limosilactobacillus reuteri NCU-37 on LIPS. The results showed that, compared to the MP group, NCU-37 significantly reduced the Modified Kupperman Index (MKI) scores (MP vs. ML = 15.00 vs. 8.00, p < 0.01), Hamilton Anxiety Scale (HAMA) scores (11.50 vs. 7.00, p < 0.01), Hamilton Depression Scale (HAMD) scores (9.00 vs. 7.00, p < 0.01), and Athens Insomnia Scale (AIS) scores (7.50 vs. 5.00, p < 0.05). Additionally, NCU-37 significantly increased serum hormone levels, including anti-Müllerian hormone (AMH), estradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH), compared to the placebo group (p < 0.05). These results indicate that NCU-37 effectively improves perimenopausal symptoms, mood disorders, and hormone levels. Meanwhile, NCU-37 altered the composition and diversity of the gut microbiota in LIPS patients, resulting in a significant increase in beneficial bacteria (Blautia) and a reduction in pathogenic bacteria (Bacteroides). Interestingly, NCU-37 increased the pregnancy rate in LIPS patients. In conclusion, this study demonstrates for the first time that the probiotic NCU-37 alleviates LIPS by improving perimenopausal symptoms, mood disorders, hormone levels, and the gut microbiota, thereby providing data to support its clinical application.

Ovarian stimulation medications are critical in assisted reproductive technology (ART), with growing demand for long-acting follicle-stimulating hormone (FSH). Although luteinizing hormone (LH) plays a pivotal role in oocyte maturation, recombinant long-acting LH remains underexplored. Here we develop a novel recombinant protein with an extended in vivo half-life and dual FSH and LH bioactivity to improve ovarian stimulation efficacy. This protein successfully induced ovarian stimulation in both mice and cynomolgus monkeys, confirming robust reproductive hormonal activity. The findings indicate its potential as an ovarian stimulation agent in ART, although further optimization of stimulation protocols is required.

Cryptorchidism is recognized as a significant risk factor for male germ cell tumors and infertility, with a complex and multifaceted mechanism contributing to male infertility. When the testes fail to descend into the scrotum, increased local temperature and pressure lead to increased apoptosis of spermatogenic and Sertoli cells. Additionally, disruptions in the hypothalamic-pituitary-gonadal axis result in decreased testosterone levels within the testes, and abnormal secretion of follicle-stimulating hormone and luteinizing hormone, negatively impacting spermatogenesis. Cryptorchidism also induces increased oxidative stress within the testes, leading to sperm DNA damage and impairment of the sperm plasma membrane, hindering sperm-oocyte fusion. Unilateral cryptorchidism may cause injury to the ipsilateral genitofemoral nerve, further affecting the contralateral testis by increasing oxidative stress and apoptosis. Moreover, the production of antisperm antibodies can trigger autoimmune responses, potentially damaging germ cells and contributing to infertility. Damage to type A dark spermatogonia (type Ad spermatogonia) is also considered a high-risk factor for male infertility. Understanding the mechanisms by which cryptorchidism leads to male infertility may provide new avenues for enhancing fertility in affected patients.

Objective This study aimed to investigate trends of metabolic syndrome (MetS) and its components across the menopausal transition and to identify key metabolic risk factors in Chinese midlife women. Method The longitudinal study included 841 women from the Peking Union Medical College Hospital Aging Longitudinal Cohort of Women in Midlife (PALM cohort, 2005–2024), classified by the Stages of Reproductive Aging Workshop +10 (STRAW +10) criteria. Repeated measures of metabolic indicators, sex hormones and sociodemographic factors were analyzed using generalized estimating equations. Results MetS prevalence rose from 15.0% in the reproductive stage to 43.9% in late postmenopause. All components except reduced high-density lipoprotein cholesterol (HDL-C) increased progressively. After adjustment, perimenopause and postmenopause stages showed higher MetS odds than the reproductive stage (p = 0.008), with the highest observed in the early postmenopause stage (odds ratio = 1.796, 95% confidence interval = 1.224–2.634), primarily driven by central obesity and elevated triglycerides. Age, follicle stimulating hormone (FSH) and estradiol (E2) were independently associated with MetS risk. Lower education and poor self-rated health correlated with higher MetS risk. Vasomotor symptoms were significantly associated with central obesity (p = 0.012) and elevated triglycerides (p < 0.001). Conclusion The menopausal transition is a critical period for metabolic deterioration. Central obesity and elevated triglycerides are key markers. Early identification and targeted intervention are essential during this transition.

This study aimed to reconstruct the hypothalamic-pituitary axis using an organ-on-a-chip (OOC) model and to evaluate the modulatory role of phoenixin-20 (PNX) in the regulation of the gonadotrophic axis in sheep. Sixteen female Polish Merino lambs were used as tissue donors to create microfluidic chips containing paired hypothalamic and pituitary slices connected via perfused channels. This system enabled continuous medium flow and maintenance of functional neuroendocrine interactions under ex vivo conditions. The OOC platform was used to analyze changes in the expression of gonadotropin-releasing hormone (GnRH), kisspeptin (Kiss), neurokinin B (NKB), and prodynorphin (pDYN) in the hypothalamus, as well as luteinizing hormone (LH) and follicle-stimulating hormone (FSH) expression and secretion in the pituitary. PNX treatment significantly increased hypothalamic GnRH expression, while the blockade of neuropeptide Y receptors (NPY1R and NPY5R) diminished this response, suggesting that PNX effects are at least partially mediated through NPY-dependent pathways. Moreover, PNX altered the transcription of Kiss, NKB, and pDYN, key components of the GnRH pulse generator, and modulated LHβ mRNA expression in the pituitary. Changes in the LH and FSH concentrations further supported a receptor-specific mechanism of PNX action. The developed hypothalamo-pituitary OOC model proved valuable for studying neuroendocrine control of reproduction. This system offers a physiologically relevant and ethically sustainable alternative to in vivo experiments, enabling precise investigations of molecular and hormonal mechanisms within the gonadotrophic axis.

AMH levels and diagnosis in PCOS phenotype D.