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Updated: Jun 8, 2026
Long-term Behavioral and Reproductive Consequences of Embryonic Exposure to Low-dose Toxicants
Published on: March 6, 2018
Exposure of neonatal female rats to bisphenol A disrupts hypothalamic LHRH pre-mRNA processing and estrogen receptor
L Monje1, J Varayoud, M Muñoz-de-Toro
1Laboratorio de Endocrinología y Tumores Hormonodependientes, School of Biochemistry and Biological Sciences, Universidad Nacional del Litoral, Santa Fe, Argentina.
Insights
Neonatal exposure to bisphenol A (BPA) permanently disrupts the neural control of estrous cyclicity in rats. BPA alters luteinizing hormone-releasing hormone (LHRH) processing and estrogen receptor expression, impacting reproductive function.
Area of Science:
- Endocrinology
- Neuroscience
- Reproductive Biology
Background:
- Neonatal exposure to endocrine disruptors can have long-lasting effects on reproductive health.
- Bisphenol A (BPA) is an endocrine-disrupting chemical with known impacts on the reproductive system.
Purpose of the Study:
- To investigate the long-term effects of neonatal bisphenol A (BPA) exposure on the hypothalamic neural network controlling estrous cyclicity.
- To determine the impact of BPA on luteinizing hormone-releasing hormone (LHRH) processing and estrogen receptor expression in adult female rats.
Main Methods:
- Neonatal female rats were exposed to vehicle, BPA.05 (0.05mg/kg/d), or BPA20 (20mg/kg/d) from postnatal day 1 to 7.
- Estrous cyclicity was assessed at postnatal day 100.
- Hypothalamic LHRH mRNA and RNA processing were analyzed using real-time PCR.
- Estrogen receptor alpha protein expression was evaluated via immunohistochemistry.
Main Results:
- BPA exposure altered estrous cyclicity and impaired the estradiol-induced LH surge in a dose-dependent manner.
- Hypothalamic expression of mature LHRH mRNA was increased in BPA.05 and decreased in BPA20-exposed rats.
- Unprocessed LHRH RNA decreased in both BPA-exposed groups, indicating disrupted pre-mRNA processing.
- Estrogen receptor alpha was differentially regulated in specific hypothalamic nuclei.
Conclusions:
- Neonatal BPA exposure causes permanent disruptions in hypothalamic LHRH pre-mRNA processing.
- BPA alters steroid receptor expression in key brain regions controlling reproductive cycles.
- These disruptions contribute to the observed long-term effects on estrous cyclicity and reproductive neuroendocrine function.
Abstract:
This study examines the effects of neonatal exposure to the endocrine disruptor bisphenol A (BPA) on the neural network that controls estrous cyclicity. From postnatal day 1 (PND1) to PND7, female pups were injected with vehicle (control) or BPA (BPA.05: 0.05mg/kg-d, BPA20: 20mg/kg-d). At PND100 BPA.05-females showed alterations in estrous cyclicity and BPA20-females were incapable of producing an estradiol-induced LH surge. By real-time PCR we determined that hypothalamic expression of mature LH-releasing hormone (LHRH) mRNA was increased in BPA.05 and decreased in BPA20-females. Furthermore, unprocessed intron A-containing LHRH RNA was decreased in the cytoplasm of hypothalamic cells of both groups. Immunohistochemistry revealed that estrogen receptor alpha protein was up-regulated in anteroventral periventricular and down-regulated in arcuate nucleus of both groups. Our results show that BPA permanently disrupts hypothalamic LHRH pre-mRNA processing and steroid receptors expression in nuclei that control estrous cyclicity in adult rats.
