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Updated: Dec 27, 2025

Long-term Behavioral and Reproductive Consequences of Embryonic Exposure to Low-dose Toxicants
Published on: March 6, 2018
Neonatal exposure to bisphenol A advances pubertal development in female rats
Jing Qiu1, Yanyan Sun1, Wen Sun1
1Department of Integrative Medicine, Children's Hospital of Fudan University, Shanghai, China.
Insights
Neonatal exposure to Bisphenol A (BPA) significantly advanced pubertal development in female rats. Higher BPA doses led to increased hormone levels and gene expression, suggesting a dose-dependent effect on puberty onset.
Area of Science:
- Endocrinology
- Developmental Biology
- Toxicology
Background:
- Neonatal exposure to endocrine-disrupting chemicals like Bisphenol A (BPA) is a growing concern.
- The precise impact of early-life BPA exposure on the timing of pubertal development requires further elucidation.
Purpose of the Study:
- To investigate the effects of neonatal Bisphenol A (BPA) exposure on the pubertal development of female Sprague-Dawley rats.
- To determine if BPA exposure influences vaginal opening, hormone levels, and key hypothalamic gene expression related to puberty.
Main Methods:
- Female Sprague-Dawley rats received daily subcutaneous injections of varying BPA doses (0.05-10 mg·kg⁻¹·day⁻¹) or vehicle from postnatal day 1 to 10.
- Evaluations at postnatal day 35 included day of vaginal opening (DVO), ovarian morphology, serum hormone assays, and quantitative analysis of hypothalamic Gnrh1 and Kiss1 mRNA and protein levels.
Main Results:
- Significant advancement in DVO was observed in rats exposed to 5 and 10 mg·kg⁻¹·day⁻¹ BPA.
- Serum hormone concentrations and hypothalamic expression of Gnrh1 and Kiss1 (both mRNA and protein) were dose-dependently increased with BPA exposure.
- The 10 mg·kg⁻¹·day⁻¹ BPA dose group exhibited significantly upregulated hypothalamic Gnrh1 and Kiss1.
Conclusions:
- Neonatal exposure to Bisphenol A (BPA) can significantly advance pubertal development in female rats.
- The effects of BPA on pubertal timing appear to be dose-dependent within the tested range.
- BPA exposure during the neonatal period may disrupt normal pubertal maturation through hormonal and neuroendocrine pathways.
Abstract:
Neonatal exposure to bisphenol A (BPA) is hypothesized to advance pubertal development. However, the effects of neonatal BPA exposure on pubertal development has not been described. In this study, female Sprague-Dawley rats were exposed to 0.05, 0.5, 5, or 10 mg·kg-1 ·day-1 BPA, or corn oil vehicle alone from postnatal day 1 (PND1) to PND10 via subcutaneous injection. We evaluated day of vaginal opening (DVO), ovarian morphology, serum hormone concentrations, and hypothalamic expression of Gnrh1 and Kiss1 in female rats at PND35. DVO was significantly advanced in rats exposed to 5 and 10 mg·kg-1 ·day-1 BPA. Serum hormone concentrations increased as BPA dose increased. Additionally, hypothalamic Gnrh1 and Kiss1 expression were increased with BPA exposure; rats exposed to 10 mg·kg-1 ·day-1 BPA had significantly upregulated hypothalamic Gnrh1 and Kiss1 expressions in terms of both messenger RNA and protein levels. Our results suggest that exposure to a 10 mg·kg-1 ·day-1 dose of BPA might advance pubertal development significantly. In addition, within the range of 0 to 10 mg·kg-1 ·day-1 , neonatal exposure to BPA may affect pubertal development in a dose-dependent manner.

