(Paris, France, Monday, 30 June 2025) — In a groundbreaking study unveiled today at the 41st Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE), researchers have uncovered compelling evidence linking polycystic ovary syndrome (PCOS) with distinctive alterations in gut microbiota and metabolic profiles that are associated with premature ageing of the endometrium and an increased risk of adverse pregnancy outcomes. This pioneering research elucidates previously unexplored biological mechanisms contributing to reproductive challenges faced by millions of women worldwide, potentially reshaping future clinical strategies in reproductive healthcare.
PCOS affects approximately 20% of women of reproductive age globally, representing a significant clinical challenge due to its association with infertility and pregnancy complications. Despite advances in fertility treatments, women with PCOS continue to experience elevated rates of miscarriage, preterm birth, gestational diabetes, and hypertensive disorders during pregnancy. The pathophysiological pathways driving these risks have remained elusive, impeding the development of targeted therapies aimed at mitigating these adverse outcomes.
At the core of this new research is the identification of a marked depletion of the beneficial gut bacterium Parabacteroides merdae (P. merdae) in women with PCOS. The gut microbiome, a complex ecosystem of microorganisms residing primarily within the gastrointestinal tract, plays a critical role in systemic metabolism, immune regulation, and overall health. P. merdae is increasingly recognized for its involvement in maintaining metabolic homeostasis, yet its role in female reproductive health had not been previously clarified until now.
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Concurrently, researchers identified an augmented concentration of branched-chain amino acids (BCAAs), with a particular emphasis on isoleucine, within the serum and endometrial tissue of PCOS patients. BCAAs, comprising isoleucine, leucine, and valine, are essential amino acids integral to protein synthesis, cellular energy metabolism, and signaling pathways. Excessive accumulation of BCAAs has been implicated in metabolic disorders such as insulin resistance and type 2 diabetes; however, their direct impact on endometrial physiology introduces a novel dimension to our understanding of PCOS-related infertility.
The comprehensive study enrolled 220 women under 35 across 44 urban centers in China, balancing an equal distribution between PCOS patients and matched healthy controls. Utilizing advanced metagenomic sequencing techniques alongside sophisticated metabolomic profiling, the research team meticulously characterized both microbial populations and circulating metabolic compounds. This dual approach allowed for an integrative examination of gut-endometrial axis interactions, shedding light on systemic and local tissue-specific alterations.
Findings revealed a significant reduction in gut microbial diversity among PCOS patients, a known hallmark of dysbiosis that impairs metabolic resilience and immune function. Of particular note was the diminished presence of P. merdae, which correlated inversely with elevated serum BCAA levels. The study also documented decreased concentrations of short-chain fatty acids (SCFAs), metabolites derived from microbial fermentation that exert anti-inflammatory and trophic effects on the gut lining and systemic tissues, suggesting a compounded disruption in metabolic regulation.
Clinically, despite comparable conception rates, women diagnosed with PCOS displayed nearly double the likelihood of encountering at least one adverse pregnancy event. These outcomes encompassed miscarriage, preterm deliveries, macrosomia, low birth weight infants, gestational diabetes mellitus, hypertensive complications, and perinatal mortality. Such findings underscore the critical importance of understanding underlying biological perturbations beyond ovulatory dysfunction alone.
Further mechanistic investigations employed laboratory cultures of human endometrial stromal cells (ESCs) exposed to elevated isoleucine levels. This in vitro model revealed induction of cellular senescence markers and a marked impairment in decidualisation, a vital differentiation process whereby the endometrium prepares for embryo implantation. These cellular signatures reflect premature ageing-like changes within endometrial tissue, offering a tangible link between metabolic disturbances and reproductive failure.
Dr. Aixia Liu, the study’s principal investigator and a specialist in reproductive endocrinology at Zhejiang University Women’s Hospital, remarked on the clinical implications: “Our data suggest that metabolic imbalances, specifically elevated isoleucine and loss of beneficial microbes like P. merdae, initiate premature endometrial ageing even in younger women with PCOS. These changes compromise the uterus’s ability to support a healthy pregnancy, explaining the persistent adverse outcomes despite successful conception.”
This research opens promising avenues for biomarker development, positing P. merdae abundance and circulating BCAA concentrations as potential predictive tools for identifying high-risk PCOS patients. Such biomarkers could refine clinical decision-making and facilitate personalized intervention strategies. The authors advocate for future exploration into dietary modulation, probiotic supplementation, or BCAA-restricted nutritional protocols aimed at restoring microbiota balance and metabolic homeostasis to enhance reproductive success.
Professor Dr. Anis Feki, Chair-Elect of ESHRE, accentuated the study’s significance by stating, “This work dramatically advances our grasp of PCOS as a systemic metabolic condition with direct repercussions on endometrial health. Linking gut microbiota dynamics to uterine function redefines the therapeutic landscape and paves the way for more nuanced, holistic treatment paradigms in reproductive medicine.”
The study will be fully accessible in the forthcoming issue of Human Reproduction, a leading journal dedicated to cutting-edge research in reproductive biology and gynecology. As PCOS continues to exert a heavy toll on women’s health globally, these revelations present a critical shift towards integrative care models that consider microbial and metabolic factors alongside hormonal therapies.
The integration of gut microbiome science with reproductive endocrinology exemplifies the expanding frontier of precision medicine, promising enhanced outcomes through novel diagnostics and targeted therapeutics. With further research, interventions tailored to recalibrate the gut-metabolite-endometrial axis may transform the landscape for women suffering from the multifaceted burdens of PCOS, ultimately improving both fertility and maternal-fetal health.
Subject of Research: Metabolic and microbial influences on premature endometrial ageing and pregnancy outcomes in women with polycystic ovary syndrome
Article Title: Unraveling the Interplay of Gut Microbiota, Metabolic Alterations, and Endometrial Senescence in Polycystic Ovary Syndrome and its Implications for Adverse Pregnancy Outcomes
News Publication Date: Monday, 30 June 2025
References:
[1] Liu, A., et al. (2025). Unraveling the interplay of gut microbiota, metabolic alterations, and endometrial senescence in polycystic ovary syndrome and its implications for adverse pregnancy outcomes. Human Reproduction.
[2] Azziz, R., Carmina, E., Chen, Z. et al. (2016). Polycystic ovary syndrome. Nat Rev Dis Primers, 2.
Keywords: Polycystic ovary syndrome, gut microbiota, Parabacteroides merdae, branched-chain amino acids, isoleucine, endometrial ageing, pregnancy complications, metabolomics, cellular senescence, reproductive endocrinology, microbiome, infertility
Tags: adverse pregnancy outcomes in womenamino acids and pregnancy complicationsclinical strategies for reproductive healthcareESHRE annual meeting research findingsgut microbiota and reproductive healthinfertility challenges in women with PCOSmetabolic profiles in PCOSmicrobiome and women’s healthParabacteroides merdae depletionpolycystic ovary syndrome and miscarriage riskpremature ageing of the endometriumtargeted therapies for PCOS
