Neonatal exposure to bisphenol a alters reproductive parameters and gonadotropin releasing hormone signaling in female rats.
BACKGROUND
Bisphenol A (BPA) is a component of polycarbonate plastics, epoxy resins, and polystyrene and is found in many products. Several reports have revealed potent in vivo effects, because BPA acts as an estrogen agonist and/or antagonist and as an androgen and thyroid hormone antagonist.


OBJECTIVE
We analyzed the effects of neonatal exposure to BPA on the reproductive axis of female Sprague-Dawley rats.


METHODS
Female rats were injected subcutaneously, daily, from postnatal day 1 (PND1) to PND10 with BPA [500 microg/50 microL (high) or 50 microg/50 microL (low)] in castor oil or with castor oil vehicle alone. We studied body weight and age at vaginal opening, estrous cycles, and pituitary hormone release in vivo and in vitro, as well as gonadotropin-releasing hormone (GnRH) pulsatility at PND13 and in adults. We also analyzed two GnRH-activated signaling pathways in the adults: inositol-triphosphate (IP(3)), and extracellular signal-regulated kinase(1/2) (ERK(1/2)).


RESULTS
Exposure to BPA altered pituitary function in infantile rats, lowering basal and GnRH-induced luteinizing hormone (LH) and increasing GnRH pulsatility. BPA dose-dependently accelerated puberty onset and altered estrous cyclicity, with the high dose causing permanent estrus. In adults treated neonatally with BPA, GnRH-induced LH secretion in vivo was decreased and GnRH pulsatility remained disrupted. In vitro, pituitary cells from animals treated with BPA showed lower basal LH and dose-dependently affected GnRH-induced IP(3) formation; the high dose also impaired GnRH-induced LH secretion. Both doses altered ERK(1/2) activation.


CONCLUSIONS
Neonatal exposure to BPA altered reproductive parameters and hypothalamic-pituitary function in female rats. To our knowledge, these results demonstrate for the first time that neonatal in vivo BPA permanently affects GnRH pulsatility and pituitary GnRH signaling.
Fernández
Marina
M
Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.
Bianchi
Maria
M
Lux-Lantos
Victoria
V
Libertun
Carlos
C
D000818:Animals; D000831:Animals, Newborn; D001559:Benzhydryl Compounds; D030762:Estrous Cycle / Q000187:drug effects; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D010636:Phenols / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D007987:Gonadotropin-Releasing Hormone; D010636:Phenols; D014874:Water Pollutants, Chemical; C006780:bisphenol A; D000098826:Bisphenol A Compounds