Diminished ovarian reserve (DOR) presents a formidable challenge for assisted reproduction technology, as affected patients typically exhibit reduced oocytes and embryos during in vitro fertilization and embryo transfer (IVF-ET), which may ultimately lead to compromised clinical pregnancy rate. Although growth hormone (GH) supplementation has shown clinical efficacy in improving the outcomes of IVF-ET, the precise molecular mechanisms underlying its ability to enhance ovarian reserve have remained poorly characterized. In this study, a cisplatin-induced DOR mice model was established via intraperitoneal cisplatin administration. GH was subsequently evaluated at four dose levels over a 21-day intervention period. Comprehensive assessments included quantitative follicular histomorphometry, serum hormone profiling, and whole-transcriptome analysis of ovarian tissue. GH treatment significantly increased the number of primary and secondary follicles in a dose-dependent manner (p < 0.05), while concurrently reducing atretic follicle counts in the medium- and high-dose GH groups compared to the DOR group (p < 0.05). Furthermore, GH treatment restored hormonal balance, characterized by decreased follicle-stimulating hormone (FSH) and increased estradiol (E2) and anti-müllerian hormone (AMH) levels (p < 0.05). Transcriptomic analysis revealed that differentially expressed genes (DEGs) between the DOR and negative control (NC) groups were primarily associated with mitochondrial energy metabolism and the reproductive endocrine system, with functional enrichment in ribosome biogenesis, oxidative phosphorylation, and thermogenesis. In contrast, DEGs between the high-dose GH and DOR groups were predominantly enriched in pathways related to immunity, mitochondrial function, protein synthesis, and extracellular matrix-receptor interactions. In conclusion, GH can restore the ovarian reserve in cisplatin-induced DOR mice in a dose-dependent manner, potentially by modulating the genetic networks involved in energy metabolism, oxidative homeostasis, and protein synthesis.

Postmenopausal metabolic dysfunction is increasingly recognized as a multisystem disorder associated with estrogen deficiency, yet how gut microbial, metabolic, and tissue-level alterations co-occur across organs remains incompletely characterized.

Autism spectrum disorder (ASD) exhibits a profound male biased sex ratio. While numerous genes have been implicated in ASD, the functional basis of this sex difference is unclear. One enticing hypothesis is genome-wide transcriptional regulation through estrogens and androgens. While hormone-mediated transcription is well-studied in reproductive tissues, its role in cortical development is poorly defined. Thus, we profiled androgen (AR) and estrogen (ESR1/ESR2) receptor expression in primary human cortex and developmental stage-matched organoid models by single-cell RNA-seq. AR was primarily expressed in radial glia and intermediate progenitors while ESR1/ESR2 was more broadly distributed across multiple cell types of the developing cortex, although with the highest expression in radial glia. To study their genetic effects, we exposed iNeurons and cortical organoids to physiological levels of dihydro-testosterone (DHT) and estradiol (E2). DHT consistently up-regulated oxidative metabolism programs enriched in progenitor cells and down-regulated neuronal maturation pathways, while E2 exhibited a much more attenuated effect. The presence of DHT reduced NTRK2 (TrkB) expression, correlating with expression in developing cortex where NTRK2 had significantly higher expression in progenitor cells of the female cortex, which is also reflected in the increased expression of AR in radial glia. Together, these data indicate that in developing human cortical lineages, sex hormones act as selective, cell-state-dependent modulators that tune metabolic and maturation programs rather than broadly reprogramming the genome. Thus, the effects of variation in transcriptional regulation through estrogens and androgens are likely to be minor, but not absent, in ASD.

Implications of menopause hormone therapy (MHT) for cognitive aging remain unclear despite decades of research. Potential reasons include insufficient consideration of MHT type, despite notable pharmacokinetic differences across formulations, and limited attention to individual differences that may exacerbate cognitive risk. We examined neurocognitive outcomes as a function of APOEϵ4 status, the strongest genetic predictor of Alzheimers disease, and MHT formulation in a sample of older (>70) females (N=8,741). Results suggest formulation- and domain-specific association between MHT and cognition, with evidence of estradiol-based MHT providing more benefits for APOEϵ4 carriers relative to conjugated equine estrogens use. Neuroimaging analyses available for a subset of participants (N=930) revealed a consistent pattern of more favourable associations (higher volume, cortical thickness; less white matter damage) in APOEϵ4 carriers taking estradiol-based MHT. These results reframe mixed MHT findings as an issue of exposure definition and support formulation- and genetic-risk-aware approaches to menopause care.

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants associated with adverse female reproductive outcomes. However, most prior studies examined individual PFAS, despite that humans are exposed to complex PFAS mixtures. Here, we investigated the ovarian effects of a mixture of five commonly detected long-chain PFAS, including PFOS, PFOA, PFNA, PFDA, and PFHxS, using complementary in vivo mouse and in vitro 3D ovarian follicle culture models. Young adult female mice were exposed to a range of concentrations of the PFAS mixture (PFASmix) through daily drinking water for 8 weeks. PFASmix at high concentrations (PFASmix-high) disrupted mouse estrous cyclicity, decreased circulating estradiol, increased testosterone, and promoted follicular atresia. Antral follicles from exposed mice showed decreased Lhcgr and increased Amh expression. Although the number of ovulated oocytes was unchanged following superovulation, PFASmix-high reduced oocyte size and polar body extrusion and altered oocyte cytoskeletal characteristics. In the 3D follicle culture model, direct PFASmix exposure impaired follicle growth, ovulation, and oocyte maturation in a concentration-dependent manner. PFASmix-high suppressed the periovulatory expression of Areg, Ereg, Tnfaip6, and Adamts1 and impaired corpus luteal (CL) development and function, as evidenced by reduced CL spheroid growth and cell survival, decreased expression of Star, Cyp11a1, Hsd3b1, and Lhcgr, and reduced progesterone secretion. PFASmix-high exposure additionally altered the expression of multiple PPARγ-associated genes in cultured ovarian follicles. Benchmark dose modeling identified estrous cyclicity and follicle rupture as sensitive in vivo and in vitro endpoints, respectively. Together, these findings demonstrated that exposure to the mixture of long-chain PFAS disrupts multiple stages of ovarian function, from follicular development, oocyte maturation to ovulation and luteal development and function and provided mechanistic and quantitative evidence for the reproductive toxicity of PFAS mixtures.

Myfembree, a fixed-dose combination of relugolix, estradiol, and norethindrone acetate, is approved for premenopausal women with heavy menstrual bleeding associated with uterine fibroids and moderate to severe pain associated with endometriosis. Although clinical trials have demonstrated its efficacy and acceptable short-term tolerability, real-world post-marketing safety evidence focused on its approved gynecologic use remains limited. This study aimed to characterize the post-marketing safety profile of Myfembree in approved gynecologic indications using the US Food and Drug Administration Adverse Event Reporting System (FAERS). A retrospective pharmacovigilance study was conducted using FAERS reports from 2021Q2 to 2025Q4. Reports listing Myfembree as the primary suspect drug were identified, and the primary analysis was restricted to approved gynecologic indication terms, including uterine leiomyoma, heavy menstrual bleeding, and endometriosis. Disproportionality analyses were performed at the system organ class and preferred term levels using reporting odds ratio, proportional reporting ratio, information component, and empirical Bayesian geometric mean. Clinically relevant preferred term signals were further prioritized according to report frequency, signal stability, seriousness, and clinical plausibility. Time to onset was assessed in reports with valid treatment initiation and event dates. A total of 1423 unique reports were included. Reporting increased after approval and peaked during 2023-2024. Most reports involved female patients (87.0%), and 10.0% were classified as serious. At the system organ class level, the strongest disproportionality signal was observed for reproductive system and breast disorders. At the preferred term level, the reporting profile was dominated by bleeding- and menstruation-related events, including heavy menstrual bleeding, intermenstrual bleeding, menstruation irregular, dysmenorrhea, and polymenorrhea. Clinically relevant nongynecologic signals included hot flush, alopecia, headache, depression, mood swings, and suicidal ideation. Thromboembolic and cardiovascular signals, particularly deep vein thrombosis, pulmonary embolism, thrombosis, and blood pressure increased, were less frequent but clinically important. Among reports with evaluable dates, the median time to onset was 19 days (interquartile range 8-55), with many major bleeding and vascular events occurring within the first few weeks after treatment initiation. In real-world post-marketing reports, Myfembree was mainly associated with abnormal uterine bleeding and menstrual cycle disturbances, together with clinically important thromboembolic, vasomotor, hair-related, and neuropsychiatric signals. These findings were generally consistent with the known safety profile of the drug and provide additional evidence on adverse event patterns and onset timing in routine gynecologic practice. Continued pharmacovigilance is warranted, particularly for thromboembolic events, blood pressure-related events, mood-related symptoms, and treatment-associated bleeding abnormalities.

A thin endometrium (TE) is associated with reduced reproductive potential, including lower implantation rates and increased obstetric risks. While intrauterine infusion of autologous platelet-rich plasma (PRP) or granulocyte colony-stimulating factor (G-CSF) is commonly used, robust evidence for their efficacy remains lacking. This trial aims to compare the effectiveness of PRP versus G-CSF in women with TE using a sham-controlled, sequential multiple assignment randomised trial (SMART) design.

When vascular tissues are damaged, plants induce site-specific formation of vascular stem cells that proliferate and differentiate into xylem and phloem, restoring vascular continuity. In addition, reactive oxygen species (ROS) are rapidly generated at wound sites in response to damage. However, the role of ROS during vascular regeneration remains largely unknown. Here, we investigated the role of ROS using an Arabidopsis inflorescence stem incision model and the vascular cell induction culture system (VISUAL). During tissue reunion of incised inflorescence stems, scavenging ROS with potassium iodide (KI) suppressed the proliferation of cambial cell layers. Consistently, the expression of cambium- and xylem-related genes, including TDR/PXY and VND7, was significantly reduced by KI treatment. Furthermore, mutation in respiratory burst oxidase homolog D (RBOHD), which encodes an ROS-producing enzyme, suppressed the proliferation of cambial cell layers. In VISUAL, KI treatment inhibited ectopic xylem formation and reduced the expression of vascular stem cell-related genes. Temporal analyses further indicated that ROS functions during the early phase of induction, as the expression of dedifferentiation-related genes such as WAK1 and ACS6 decreased under KI treatment. Notably, the expression of Arabidopsis NAC domain-containing protein 071 (ANAC071) and ANAC096 was not suppressed by KI in incised stems, and estradiol-induced expression of ANAC071 failed to rescue vascular differentiation in VISUAL under KI treatment. These findings demonstrated that ROS act prior to ANAC function during the early phase of vascular regeneration.

The oviduct provides an optimal environment to protect gametes and embryos against oxidative stress, yet its endogenous defenses remain insufficiently characterized. This study examined the expression and the spatial, temporal and hormonal regulation of four major antioxidant enzyme families - peroxiredoxins (PRDX), catalase (CAT), superoxide dismutases (SOD), and glutathione peroxidases (GPX) - in the bovine oviduct. Oviducts from cyclic cows were analyzed in three complementary experiments. In vivo (Experiment 1), mRNA expression of antioxidant enzymes (CAT, GPX1-3, PRDX1-6, SOD1-2) was compared between oviductal regions (ampulla vs. isthmus) and estrous cycle stages (pre-ovulatory, post-ovulatory, luteal). In vitro (Experiment 2), physiological concentrations of progesterone (100 ng/mL) and estradiol (300 pg/mL) were tested on gene expression in ampullary and isthmic epithelial spheroids. In Experiment 3, GPX protein abundance and enzymatic activity were assessed in oviductal fluid. All transcripts were detected in the oviduct epithelium. GPX1-3 and PRDX6 showed region-specific expression, with GPX1-2 enriched in the ampulla and GPX3 and PRDX6 in the isthmus. Stage-dependent variations were observed for CAT, SOD2, PRDX2, PRDX4, and PRDX6 in a region-dependent manner. Progesterone upregulated GPX2 and PRDX6 in both ampullary and isthmic spheroids, while estradiol selectively stimulated PRDX4 expression in isthmic spheroids. GPX3 protein abundance decreased at the post-ovulatory stage, in both regions, and mirrored the GPX activity in the oviduct fluid. These results demonstrate that antioxidant enzyme expression in the bovine oviduct is dynamically regulated by region, cycle stage, and hormonal milieu, highlighting their role in maintaining redox homeostasis during early reproductive events.

To investigate the combined effects of soybean lecithin (SL) with vitamin C (VC) or inositol (INO) on growth, gonadal development, and intestinal microbiota, 2-year-old longsnout catfish (Leiocassis longirostris) were fed four isonitrogenous and isolipidic diets for 12 weeks, including a control diet, a 4% SL diet, a 4% SL + 0.5% VC (SC) diet, and a 4% SL + 0.5% INO (SI) diet. A two-way analysis of variance (ANOVA) revealed a significant diet × sex interaction for weight gain rate (WGR) and specific growth rate (SGR) (p < 0.05). In females, the SI group exhibited the highest WGR and SGR, while both the SC and SI groups showed significantly higher WGR and SGR than both the SL and control groups in males (p < 0.05). All three supplemented groups promoted gonadal development, as reflected by higher gonadosomatic index (GSI) and elevated serum 17β-estradiol (E2) and progesterone (P4) levels. Both SC and SI groups showed significantly increased total antioxidant capacity (T-AOC), superoxide dismutase (SOD), catalase (CAT), and alkaline phosphatase (AKP) activities and significantly decreased malondialdehyde (MDA) and cortisol levels compared with the control group (p < 0.05). Dietary SC enriched potentially beneficial Bacteroides in both sexes. SI enriched potentially beneficial Cetobacterium in males. Furthermore, all three supplemented diets reduced the potentially pathogenic Plesiomonas in females. Gonadal transcriptome analysis suggested that SL combined with VC or INO may modulate pathways such as the peroxisome proliferator-activated receptor (PPAR) signaling pathway, biosynthesis of unsaturated fatty acids, estrogen signaling, and histidine metabolism, implying potential roles in gonadal lipid metabolism, chaperone-mediated protection, and immune homeostasis. Overall, SI was most effective in promoting growth in females, whereas both SC and SI were more effective in promoting gonadal maturation, enhancing antioxidant capacity, and improving intestinal microbiota composition. This study provides theoretical guidance for the development of specialized compound feeds during the gonadal development period in longsnout catfish aquaculture.