Living in a chemical cocktail: real-world mixture exposures and their impact on ovarian function

Poor reproductive health is related to ovarian function, which may manifest as early/late puberty, premature ovarian insufficiency, and/or early menopause, and is increasingly observed worldwide. Mounting evidence implicates exposure to endocrine disrupting chemicals (EDCs) in these outcomes. EDCs are now ubiquitous in the environment, resulting in chronic low-level exposure of humans and animals to many chemicals. These compounds perturb endogenous hormone signaling, leading to both local and systemic endocrine disruption. Consequently, the hypothalamic-pituitary-ovarian (HPO) axis represents a primary target, with downstream consequences for ovarian function. Traditional toxicological approaches often rely on acute, high-dose exposures to single compounds, which fail to capture the complex reality of low-dose exposure to diverse chemical mixtures. Recognizing this gap, recent research has started to leverage more "real-life" exposure models that better represent these environmental conditions. This review summarizes current evidence on the impact of EDCs on reproductive health with a focus on ovarian function, highlights existing animal models that capitalize on more real-life exposure scenarios, and explores critical research considerations and future directions to advance our understanding of how real-world EDC mixtures disrupt ovarian function and female reproductive health.