Background: The characteristics of polycystic ovary syndrome (PCOS), a common reproductive endocrinal disorder, are high incidence, complicated aetiology and poor therapeutic effects. PCOS patients frequently exhibit gut dysbiosis; however, its roles in the regulation of metabolic and endocrinal balances in PCOS pathophysiology are not clear. Results: In this study, gut dysbiosis was reproduced in dehydroepiandrosterone (DHEA)-induced PCOS-like rats. An antibiotic cocktail was used to eliminate gut microbiota during DHEA treatment; however, depletion of the gut microbiota did not prevent the occurrence of PCOS phenotypes in DHEA-treated rats. DHEA-shaped gut microbiota transplanted to pseudo germ-free recipients trigged disturbances in hepatic glucolipid metabolism and reproductive hormone imbalance. The clinical features of PCOS may be correlated with the relative abundance of gut microbes and the levels of faecal metabolites in faecal microbiota transplantation (FMT) recipient rats. Conclusion: These findings indicate that androgen-induced gut microbiota dysbiosis may aggravate metabolic and endocrinal malfunction in PCOS.

To identify different microbial species in women with polycystic ovary syndrome (PCOS) and reveal a possible relationship between gut dysbiosis and pathological changes. Cross-sectional study. Academic institution. Reproductive-aged women with PCOS (n = 14) and controls (n = 14) from the Centre for Reproductive Medicine. Shotgun metagenomic sequencing on fecal samples from patients, and clinical parameters (including body mass index, endocrine hormone levels, and glycemia level) gathered for correlation analysis. Identification of different gut microbial strains and relativity between microbiota and clinical parameters. We found several microbial strains were statistically significantly more abundant in the PCOS group, including Parabacteroides merdae, Bacteroides fragilis, and strains of Escherichia and Shigella, whereas Faecalibacterium prausnitzii was enriched in the control group. Metagenomic species (MGS) analysis revealed that the microbes of the PCOS group were negatively correlated with those of the control group. Of note, we observed a positive correlation between MGS relevant to PCOS and endocrine disorders, including body mass index and elevated levels of serum testosterone, luteinizing hormone, and antimüllerian hormone. Functional alterations, reflected by Kyoto Encyclopedia of Genes and Genomes orthologues, could imply potential mechanisms of microbial involvement in the developmental progress of PCOS. Our findings suggest an intimate association and potential mechanisms linking microbial dysbiosis and the pathophysiologic changes of PCOS. We address the importance of monitoring and modulating microbial composition and functional shifts in future clinical practice.

To better understand possible effects of bisphenol A (BPA) exposure on ovarian reserve in women with polycystic ovary syndrome (PCOS), we measured creatinine adjusted urinary BPA (BPA_Cre) concentrations and used regression models to evaluate the association between urinary BPA level and antral follicle count (AFC), antimullerian hormone (AMH), day-3 follicle stimulating hormone levels (FSH) and inhibin B (INHB) in 268 infertile women diagnosed with PCOS. BPA was detected in all women with a median concentration of 2.35 ng/mL (the 25th and 75th percentiles of 1.47 ng/mL and 3.95 ng/mL). A unit increase in BPA_Cre was associated with a significant decrease of 0.34 in AFC (β = −0.34, 95% CI = −0.60, −0.08; p = 0.01). Likewise, BPA was negatively associated with AMH and day-3 FSH levels, but neither of them reached statistical significance. No association was observed between BPA and INHB. Our results suggest that in women with PCOS, BPA may affect ovarian follicles and, therefore, reduce ovarian reserve.

Polycystic ovary syndrome (PCOS) is an endocrine-related disease and global cause of infertility that is associated with abnormal folliculogenesis. Inhibited granulosa cell (GC) proliferation is recognized as a key factor that underlies aberrant follicle maturation. Many epigenetic landscape modifications have been characterized in PCOS patients. However, the epigenetic regulation pathways in follicular dysplasia are not completely understood. In this study, we reported a novel mechanism of DNA hypomethylation induced by long non-coding RNAs (lncRNAs) and its function in cell cycle progression. We observed that lnc-MAP3K13-7:1 was highly expressed in GCs from patients with PCOS, with concomitant global DNA hypomethylation, decreased DNA methyltransferase 1 (DNMT1) expression and increased cyclin-dependent kinase inhibitor 1A (CDKN1A, p21) expression. In KGN cells, lnc-MAP3K13-7:1 over-expression resulted in cell cycle arrest in G0/G1 phase, as well as the molecular inhibition and genetic silencing of DNMT1. Mechanistically, lnc-MAP3K13-7:1 inhibited DNMT1 expression by acting as a protein-binding scaffold and inducing ubiquitin-mediated DNMT1 protein degradation. Moreover, DNMT1-dependent CDKN1A promoter hypomethylation increased CDKN1A transcription, resulting in attenuated GC growth. Our work uncovered a novel and essential mechanism through which lnc-MAP3K13-7:1-dependent DNMT1 inhibition regulates CDKN1A expression and inhibits GC proliferation.

Autophagy is a fundamental process that exists in all eukaryotic organisms, with a primary function of catabolizing undesirable components to provide energy and essential materials. Increasing evidence illustrates that autophagy is invovled in a broad range of cellular events within the male reproductive system. In the process of spermatogenesis, autophagy is crucial for the formation of specific structures that guarantee successful spermatogenesis, as well as for the degradation of certain constituents. The underlying connections between autophagy and androgen binding protein, lipid metabolism and testosterone biosynthesis would increase our understanding of male testicular endocrinology. Moreover, cumulative studies reveal that autophagy is a double-edged sword when the organism suffers from endocrine disrupting chemicals. This review contains a collection of the current literature concerning the above aspects of autophagy, which may provide insights for future study and exploration. Abbreviations: 3-MA: 3-methyladenine; ABP: androgen-binding protein; AKT: protein kinase B; AMPK: adenosine monophosphate-activated protein kinase; ART: assisted reproductive technologies; Atg: autophagy-related gene; CE: cholesteryl ester; CL: corpus luteum; CQ: chloroquine; CYP11A1: cholesterol side chain cleavage enzyme; CytC: cytochrome C; DEHP: di-2-ethylhexyl phthalate; DFCP1: double FYVE-containing protein 1; EDCs: endocrine-disrupting chemicals; ERK1/2: extracellular signal-regulated kinase 1/2; ES: ectoplasmic specialization; FC: free cholesterol; FIP2000: focal adhesion kinase family interacting protein of 200kDa; FSH: follicle stimulating hormone; HDL: high-density lipoprotein; IVF: in vitro fertilization; LC3: microtubule-associated protein light chain 3; LD: lipid droplet; LH: luteinising hormone; MC-LR: microcystin-LR; MEFs: mouse embryonic fibroblast cells; MT: microtubule; mtDNA: mitochondrial DNA; mTOR: mammalian target of rapamycin; NHERF2: Na⁺/H⁺ exchanger regulatory factor 2; NMR: naked mole-rat; PCD: programmed cell death; PDLIM1: PDZ and LIM domain 1; PGCs: primordial germ cells; PGF_2α: prostaglandin F_2α; PI3K: phosphatidylinositol-3-kinase; PI3P: phosphatidylinositol-3-phosphate; ROS: reactive oxygen species; SCG10: superior cervical ganglia protein 10; SR-BI: scavenger receptor class B, type I; StAR protein: steroidogenic acute regulatory protein; TC: total cholesterol; TEM: transmission electron microscopy; TUNEL: terminal deoxynucleotidyl transferase mediated dUTP nick end labeling; ULK1: mammalian uncoordinated-51-like kinase 1; WIPI: WD-repeat domain phosphoinositide-interacting.