Impact of fine particulate matter on blastocyst development in women undergoing In Vitro fertilization

Fine particulate matter (PM_2.5) has increasingly been implicated in adverse reproductive outcomes. It is associated with irregular periods, reduced fertility, problems with egg production, and decreased embryo quality. However, its effects on the earliest stages of human embryogenesis remain poorly defined. In this study, we analyzed a real-world cohort of 885 first-cycle in-vitro fertilization (IVF) patients using high-resolution geocoded exposure data to evaluate the effects of primary ambient pollutants and identify those most strongly associated with blastocyst development. Higher maternal exposure to combustion-derived pollutants (especially PM_2.5) was consistently associated with reduced blastocyst formation and lower rates of high-quality blastocyst in both primary and secondary infertility groups. To further investigate these findings, we conducted a litter-controlled mouse experiment in which the mice were exposed to long-term ambient PM_2.5 (mean 29.71 µg/m³). Blastocysts from exposed females exhibited a pronounced glycolytic shift, characterized by increased expression of glycolytic enzymes. We also observed activation of Hypoxia-inducible factor 1-alpha (HIF-1α), increased oxidative stress, suppressed mitochondrial function and tricarboxylic acid-cycle activity, and disrupted proteostasis. These alterations were confirmed by proteomics, quantitative PCR, and functional imaging. Collectively, this finding demonstrates that PM_2.5 exposure compromises early blastocyst development through metabolic reprogramming, mitochondrial impairment, and proteotoxic stress. The cross-species convergence of epidemiologic and molecular evidence indicates pollutant-specific reproductive toxicity and highlights actionable opportunities for exposure mitigation in IVF care. The graphical abstract is presented in Fig. 1.