The Effects of Microplastics and Trace Elements on Ovarian Function and Pathology: A Literature Review

The female reproductive system, particularly the ovary, exhibits a high sensitivity to the effects of environmental xenobiotics. This group of substances includes micro- and nanoplastics (MNPs) as well as trace elements. This literature review summarises the current knowledge on the individual and combined effects of MNPs and trace elements-including essential bioelements (zinc (Zn), selenium (Se), copper (Cu), chromium (Cr), manganese (Mn)) and toxic elements (cadmium (Cd), Lead (Pb), arsenic (As), mercury (Hg))-on ovarian physiology and clinical conditions such as polycystic ovary syndrome (PCOS), gonadal dysfunction and infertility. Essential trace elements play irreplaceable roles as enzyme cofactors (e.g., superoxide dismutase (SOD), glutathione peroxidase (GPX)) and transcriptional regulators; however, their biological action is confined to a narrow homeostatic window, within which both deficiency and excess disrupt cellular redox status and the hypothalamic-pituitary -gonadal axis. The effect of toxic heavy metals is different; these exhibit threshold-independent cytotoxic, genotoxic and endocrine-disrupting effects, inducing apoptosis of granulosa cells, endoplasmic reticulum stress and the silencing of steroidogenic genes (e.g., Steroidogenic acute regulatory protein (StAR), CYP11A1, CYP19A1) via epigenetic modifications, which accelerates the depletion of the ovarian reserve (measured by a decline in anti-Müllerian hormone (AMH)). Concurrently, MNPs overcome biological barriers and accumulate within the ovarian microenvironment, thereby inducing reactive oxygen species (ROS)-dependent apoptosis, NLR family pyrin domain-containing 3 (NLRP3) inflammasome-mediated pyroptosis, cytoskeletal disruption, and tissue fibrosis. A key element of this review is the identification of mechanistic convergence and potential toxic synergism between MNPs and heavy metals. Co-exposure enhances toxin retention within cells by inhibiting ATP-binding cassette (ABC) transporters, potentiates mitochondrial depolarisation, and activates protein kinase RNA-like endoplasmic reticulum kinase-eukaryotic translation initiation factor 2 alpha (PERK/eIF2α) stress signalling. Understanding these shared molecular pathways forms the basis for assessing multi-component risk in female reproductive toxicology and for developing targeted protective strategies.