Impact of prenatal Di(2-ethylhexyl) phthalate exposure on pubertal development in female offspring rats: A focus on ERα-Mediated IGF-1/NKB crosstalk in the hypothalamus.

Di(2-ethylhexyl) phthalate (DEHP), renowned for its efficacy in enhancing the pliability of plastic products, serves predominantly as a plasticizer and additive in the plastics industry. A growing body of research in both animal models and human populations has elucidated that the maternal environment prior to birth exerts a significant influence on the growth and development of offspring. Consequently, our research is designed to investigate the effects of prenatal DEHP exposure on the pubertal reproductive development of female rat offspring and to decipher the underlying mechanisms. This study utilized Wistar rats as the experimental animal model, with exposure to varying doses of DEHP during pregnancy for group allocation and treatment. Transmission electron microscopy was used to examine ultrastructural changes in the hypothalamus of DEHP-exposed female offspring rats. High-performance liquid chromatography (HPLC) was employed to quantitatively analyze the amino acid levels in the hypothalamus of the female offspring. Enzyme-linked immunosorbent assay (ELISA) was used to quantitatively measure hormone levels in both the hypothalamus and peripheral blood. Immunohistochemistry was applied to quantify the expression of ERα and GnRH in the hypothalamus. Additionally, precise immunofluorescence analysis was conducted to assess the expression levels of IGF-1 and NKB in the rat hypothalamus. Spearman correlation analysis was employed to elucidate the associations between key factors in the hypothalamus. Our findings reveal that prenatal exposure to Di(2-ethylhexyl) phthalate (DEHP) precipitates the onset of puberty in female rat offspring, concurrently altering the expression of key puberty-regulating genes in the hypothalamus. This elucidation sheds light on the molecular mechanisms underpinning the role of hypothalamic ERα in modulating the IGF-1 and NKB pathways, contributing to DEHP-induced precocious puberty in females, and underscores the critical regulatory function of IGF-1/NKB crosstalk in this phenomenon. Consequently, our research posits that prenatal exposure to DEHP is likely transmitted from the mother to the embryo, precipitating developmental anomalies and the onset of precocious puberty in offspring. This underscores the significance of pregnancy as a pivotal period for endocrine disruption, offering a novel theoretical foundation for the prophylaxis and management of precocious puberty in female children.