Impairment of zebrafish (Danio rerio) oogenesis and F1 embryonic development by maternal methylparaben exposure:...

Methylparaben (MP) is a commonly utilized preservative that has been associated with potential toxic effects on the reproductive, nervous, and endocrine systems. However, research on the intergenerational toxic impacts of MP exposure, particularly in zebrafish, remains limited. To address this gap and to elucidate the underlying mechanisms, this study aimed to investigate the effects of MP exposure on female reproductive impairment and embryonic developmental toxicity. Maternal zebrafish were subjected to environmentally relevant concentrations of MP (1 and 100 μg/L) for 4 weeks. Following this exposure, the exposed female zebrafish (F0♀+) were paired with unexposed male zebrafish (F0♂-), and their fertilized F1 progeny were reared in uncontaminated water for 120 h. Compared with the control group (F0♀-), F0♀+ exhibited a diminished proportion of mature oocytes and reduced egg production, alongside decreased estrogen levels and activation of the focal adhesion signaling pathway. Moreover, maternal exposure to MP was associated with developmental anomalies in the F1 offspring, including yolk sac and pericardial edema, an increased heart rate, and reduced body length. Additionally, there was an enhancement in spontaneous movement and an inhibition of motor behavior in the F1 larvae. Corroborating these phenotypic observations, maternal MP exposure induced global transcriptomic alterations related to growth and development processes, cardiac development, nervous system processes, and metabolic signaling pathways in the unexposed F1 offspring. Notably, the focal adhesion, extracellular matrix (ECM)-receptor interaction, and phosphoinositide 3-kinase (PI3K)-Akt signaling pathways were significantly enriched in these unexposed F1 offspring. Collectively, this study reveals that subchronic MP exposure impairs oogenesis and reduces fertility in adult female zebrafish, while also causing embryonic developmental toxicity in their F1 progeny. As the investigation into the intergenerational effects of maternal MP exposure in zebrafish, it establishes a crucial foundation for assessing the ecotoxicological impacts of MP.