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Updated: May 27, 2026
Long-term Behavioral and Reproductive Consequences of Embryonic Exposure to Low-dose Toxicants
Published on: March 6, 2018
Neonatal Bisphenol A exposure alters sexually dimorphic gene expression in the postnatal rat hypothalamus
Jinyan Cao1, Jillian A Mickens, Katherine A McCaffrey
1Department of Biology, North Carolina State University, Raleigh, NC 27695, USA.
Insights
Neonatal exposure to Bisphenol A (BPA) disrupts key gene expression in the rat hypothalamus, potentially affecting reproductive development. BPA alters estrogen receptor and Kiss1 expression differently than estradiol benzoate, suggesting a unique mechanism of action.
Area of Science:
- Endocrinology
- Neuroscience
- Toxicology
Background:
- Neonatal exposure to Bisphenol A (BPA) may disrupt reproductive function in female rodents.
- The neonatal period is critical for organizing the hypothalamic-pituitary-gonadal (HPG) axis.
- Understanding BPA's effects on gene expression in the hypothalamus is crucial for assessing reproductive health risks.
Purpose of the Study:
- To investigate if neonatal BPA exposure alters sex-specific gene expression of estrogen receptors (ERα, ERβ) and kisspeptin (Kiss1) in the rat hypothalamus.
- To compare the effects of BPA with estradiol benzoate (EB) on hypothalamic gene expression.
Main Methods:
- Neonatal Long Evans rats were exposed to vehicle, EB, or BPA from postnatal day 0 to 2.
- Gene expression of ERα, ERβ, and Kiss1 in the anterior and mediobasal hypothalamus was assessed using in situ hybridization on postnatal days 4 and 10.
Main Results:
- BPA augmented ERα expression in PND 4 females, which normalized by PND 10.
- BPA significantly decreased or eliminated ERβ expression in both sexes by PND 10.
- BPA diminished Kiss1 expression in the anterior hypothalamus, particularly in females.
- BPA did not significantly impact gene expression in the mediobasal hypothalamus.
- BPA's effects differed from those of EB.
Conclusions:
- Neonatal BPA exposure alters hypothalamic expression of ERα, ERβ, and Kiss1.
- These disruptions may interfere with the sexual dimorphic organization of the hypothalamus.
- BPA likely disrupts hypothalamic organization via a mechanism distinct from estrogen mimicry.
Abstract:
Developmental exposure to Bisphenol A (BPA), a component of polycarbonate and epoxy resins, has been purported to adversely impact reproductive function in female rodents. Because neonatal life is a critical window for the sexual dimorphic organization of the hypothalamic-pituitary-gonadal (HPG) axis, interference with this process could underlie compromised adult reproductive physiology. The goal of the present study was to determine if neonatal BPA exposure interferes with sex specific gene expression of estrogen receptor alpha (ERα), ER beta (ERβ) and kisspeptin (Kiss1) in the anterior and mediobasal hypothalamus. Long Evans (LE) neonatal rats were exposed to vehicle, 10microg estradiol benzoate (EB), 50mg/kg BPA or 50microg/kg BPA by subcutaneous injection daily from postnatal day 0 (PND 0) to PND 2. Gene expression was assessed by in situ hybridization on PNDs 4 and 10. Within the anterior hypothalamus ERα expression was augmented by BPA in PND 4 females, then fell to male-typical levels by PND 10. ERβ expression was not altered by BPA on PND 4, but significantly decreased or eliminated in both sexes by PND 10. Kiss1 expression was diminished by BPA in the anterior hypothalamus, especially in females. There were no significant impacts of BPA in the mediobasal hypothalamus. Collectively, BPA effects did not mirror those of EB. The results show that neonatal hypothalamic ER and Kiss1 expression is sensitive to BPA exposure. This disruption may alter sexually dimorphic hypothalamic organization and underlie adult reproductive deficiencies. Additionally, the discordant effects of EB and BPA indicate that BPA likely disrupts hypothalamic organization by a mechanism other than simply acting as an estrogen mimic.
