Evaluation of the reproductive toxicity of endocrine disruptors during early embryo development

Abstract Because the blastocyst is a critical stage of early embryonic development, developmental abnormalities can serve as sensitive biomarkers of reproductive toxicity. This review focuses on the impact of various endocrine disrupting chemicals (EDCs) including phthalates, bisphenols, parabens and per- and polyfluoroalkyl substances on blastocyst formation, structure, and function. Murine blastocyst development models offer a controlled and reproducible platform to study cell differentiation, implantation potential, and epigenetic regulation. In vitro systems allow simulation of internal EDC concentrations found in human biological fluids, enabling dose-response relationships that reflect real world exposure. EDCs present in reproductive fluids such as follicular, oviductal, and endometrial fluid can impair oocyte quality and compromise embryonic development, even in morphologically normal embryos. Blastocysts exposed to EDCs during development show alterations in lineage specification markers (e.g., OCT4, SOX2, CDX2), cytoskeletal organization, and nuclear integrity, suggesting disruption of key developmental pathways. This review systematically reviews in vitro and in vivo evidence, along with proposed mechanisms of action, for each group of EDCs. Importantly, only studies reporting blastocyst formation rates were included to ensure relevance and comparability. The synthesis identifies common toxicity patterns, potential synergistic effects, and transgenerational consequences. The findings have direct implications for human fertility, particularly in the context of assisted reproductive technologies (ART), and highlight the need for improved regulatory frameworks and biomarker validation. Overall, the blastocyst emerges as a powerful tool for understanding and mitigating the reproductive risks associated with environmental chemical exposure.