Microplastics and nanoplastics in follicular fluid are associated with diminished ovarian reserve: clinical and molecular insights.

INTRODUCTION

Ovarian aging is a significant concern, yet the influencing factors remain unclear. Environmental factors are crucial determinants of diminished ovarian reserve (DOR). Microplastics and nanoplastics (MNPs) are widespread in the environment and pose health risks. The effect of MNPs on ovarian function remains uncertain.

OBJECTIVES

The study aims to investigate whether exposure to MNPs negatively affects ovarian function. In particular, the research focuses on elucidating the association between MNPs-especially polyamide 66-and DOR, and validating Parabacteroides goldsteinii (P. goldsteinii) as a potential intervention.

METHODS

We conducted a case-control study analyzing MNPs in follicular fluid from 110 DOR patients and 110 age-matched controls. A mouse MNPs-exposure model assessed ovarian function and intestinal barrier integrity. Gut microbiota alterations were analyzed by metagenomic sequencing of fecal samples from MNPs-exposed mice. P. goldsteinii was identified and selected for microbial intervention, administered via oral gavage. The human granulosa cell line (KGN) was treated with MNPs for 48 h, followed by transcriptomic sequencing to examine PI3K/AKT/mTOR pathway alterations.

RESULTS

Human follicular fluid contained multiple MNPs, with polyamide 66 (PA66) levels significantly linked to DOR. Polystyrene (PS) and polyvinyl chloride (PVC) concentrations were also higher in the DOR group. MNPs induced DOR-like phenotypes in mice, causing hormonal imbalances, disrupted estrous cycles, and increased atretic follicles, alongside intestinal barrier damage and gut microbiota dysbiosis. Notably, the abundance of P. goldsteinii and its key metabolite 7-keto-lithocholic acid was significantly reduced following MNPs exposure. Supplementation with P. goldsteinii effectively reversed MNPs-induced DOR-like phenotypes, restored hormonal homeostasis, normalized estrous cyclicity, reduced follicular atresia, and elevated 7-keto-LCA levels. Mechanistically, MNPs triggered the PI3K/AKT/mTOR pathway, impairing granulosa cell function and ovarian reserve.

CONCLUSION

These findings elucidate how exposure to MNPs may harm female ovarian function and provide potential new strategies for ameliorating reproductive disorders through the environment‒gut‒ovarian axis.