Neonatal Bisphenol-A Exposure Alters Rat Reproductive Development and Ovarian Morphology Without Impairing Activation of Gonadotropin-Releasing Hormone Neurons

Department of Biology, North Carolina State University, Raleigh, North Carolina, USA.
Biology of Reproduction (Impact Factor: 3.45). 07/2009; 81(4):690-9. DOI: 10.1095/biolreprod.109.078261
Source: PubMed

ABSTRACT Developmental exposure to endocrine-disrupting compounds is hypothesized to adversely affect female reproductive physiology by interfering with the organization of the hypothalamic-pituitary-gonadal axis. Here, we compared the effects of neonatal exposure to two environmentally relevant doses of the plastics component bisphenol-A (BPA; 50 microg/kg and 50 mg/kg) with the ESR1 (formerly known as ERalpha)-selective agonist 4,4',4''-(4-propyl-[(1)H]pyrazole-1,3,5-triyl)trisphenol (PPT; 1 mg/kg) on the development of the female rat hypothalamus and ovary. An oil vehicle and estradiol benzoate (EB; 25 microg) were used as negative and positive controls. Exposure to EB, PPT, or the low dose of BPA advanced pubertal onset. A total of 67% of females exposed to the high BPA dose were acyclic by 15 wk after vaginal opening compared with 14% of those exposed to the low BPA dose, all of the EB- and PPT-treated females, and none of the control animals. Ovaries from the EB-treated females were undersized and showed no evidence of folliculogenesis, whereas ovaries from the PPT-treated females were characterized by large antral-like follicles, which did not appear to support ovulation. Severity of deficits within the BPA-treated groups increased with dose and included large antral-like follicles and lower numbers of corpora lutea. Sexual receptivity, examined after ovariectomy and hormone replacement, was normal in all groups except those neonatally exposed to EB. FOS induction in hypothalamic gonadotropic (GnRH) neurons after hormone priming was impaired in the EB- and PPT-treated groups but neither of the BPA-treated groups. Our data suggest that BPA disrupts ovarian development but not the ability of GnRH neurons to respond to steroid-positive feedback.

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    ABSTRACT: The study was conduct to determine the effect of exposure to Bisphenol A (BPA) during gestation on serum reproductive hormones levels (Estradiol" E2", Luteinizing Hormone "LH" and follicle-stimulating Hormone" FSH"), age and weight at vaginal opening onset as well as reproductive efficacy in F1 female offspring. Thirty six pregnant female rats (F0) were gavage three doses of BPA suspended in corn oil (50 µg, 50 mg, 250 mg/kg/BW) or corn oil only as control group from gestational day (GD) 6 till gestation day (GD) 21. After delivery, twelve female pups of each group were hold for three months; However, Female rats' offspring, after weaning, were weighed and checked for vaginal opening (VO) every day until completion, then at postnatal day (PND) 90, blood samples were collected from six F1 female of each group to perform hormonal tests and other six females were mated with untreated male rat in a separate cage for 14 days in order to evaluate fertility efficacy. The results showed significant increased (P<0.05) in serum E2 levels, and decrease in LH level, but FSH levels were unchanged in all treated groups compared with control group. The results also revealed significant decrease age at VO onset in all treated groups compared with control group , while body weight at age of VO onset was non-significantly differ between all groups. Fertility rate, number of birth and implantation sites were reduced and resorption sites were elevated in F1 female rats that gestationally exposed to deferent levels of BPA in comparison with control group. From the present study it has been revealed that the BPA exposures during pregnancy adversely affect F1 female reproduction and caused early puberty onset.
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    ABSTRACT: Bisphenol-A (BPA) is a monomer used in the production of polycarbonate plastics, epoxies and resins and is present in many common household objects ranging from water bottles, can linings, baby bottles, and dental resins. BPA exposure has been linked to numerous negative health effects throughout the body, although the mechanisms of BPA action on the developing brain are still poorly understood. In this study, we sought to investigate whether low dose BPA exposure during a developmental phase when brain connectivity is being organized can cause long-term deleterious effects on brain function and plasticity that outlast the BPA exposure. Lactating dams were orally exposed to 25 μg/kg/day of BPA (one half the U.S. Environmental Protection Agency's 50 μg/kg/day rodent dose reference) or vehicle alone from postnatal day (P)5 to P21. Pups exposed to BPA in their mother's milk exhibited deficits in activity-dependent plasticity in the visual cortex during the visual critical period (P28). To determine the possible mechanisms underlying BPA action, we used immunohistochemistry to examine histological markers known to impact cortical maturity and developmental plasticity and quantified cortical dendritic spine density, morphology, and dynamics. While we saw no changes in parvalbumin neuron density, myelin basic protein expression or microglial density in BPA-exposed animals, we observed increases in spine density on apical dendrites in cortical layer five neurons but no significant alterations in other morphological parameters. Taken together our results suggest that exposure to very low levels of BPA during a critical period of brain development can have profound consequences for the normal wiring of sensory circuits and their plasticity later in life.
    Frontiers in Neuroanatomy 10/2014; 8:117. DOI:10.3389/fnana.2014.00117 · 4.18 Impact Factor
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    ABSTRACT: To investigate the potential protective effects of Tualang honey against the toxicity effects induced by Bisphenol A (BPA) on pubertal development of ovaries. This study was conducted on pre-pubertal female Sprague Dawley rats. Animals were divided into four groups (n = 8 in each group). Group I was administered with vehicle 0.2 ml of corn oil (Sigma-Aldrich, USA) using oral gavage daily for six weeks; these animals served as negative control (CO group), Group II was administered with BPA suspended in corn oil at 10 mg/kg body weight and served as positive control (PC group), Group III was administered with 200 mg/kg body weight of Tualang honey 30 min before the administration of BPA at 10 mg/kg (TH group) while Group IV was administered with 200 mg/kg body weight of Tualang honey 30 min before the administration of corn oil (THC group). Body weight of all animals were monitored weekly. The BPA-exposed animals exhibited disruption of their estrus cycle, while those animals treated with BPA together with Tualang honey, exhibited an improvement in percentage of normal estrous cycle. Their ovaries had lower numbers of atretic follicles compared to the PC group but higher than the CO group. Tualang honey has a potential role in reducing BPA-induced ovarian toxicity by reducing the morphological abnormalities of the ovarian follicles and improving the normal estrous cycle.
    BMC Complementary and Alternative Medicine 12/2014; 14(1):509. DOI:10.1186/1472-6882-14-509 · 1.88 Impact Factor

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