Bisphenol A Exposure during Adulthood Causes Augmentation of Follicular Atresia and Luteal Regression by Decreasing 17β-Estradiol Synthesis via Downregulation of Aromatase in Rat Ovary

Abstract

Materials and Methods Materials. Monoclonal anti-actin (mouse IgG2a isotype), anti-β-tubulin, BPA, Bouin's solution, corn oil, dimethyl sulfoxide (DMSO), hematoxylin, HEPES, medium 199, trypan blue, and Tween-20 were purchased from Sigma Chemical Co. (St. Louis, MO, USA). We purchased anti-aromatase from Acris Antibodies (San Diego, CA, USA); anticalbindin-D9k from Swant Swiss Antibodies (Bellinzona, Switzerland); antibody specific for cleaved (active form) caspase-3 antibody from Cell Signaling (Beverly, MA, USA); anti-FSH (follicle-stimulating hormone) antibody from AbD Serotec (Kidlington, UK); anti-3β-HSD, anti-CYP17A1, proliferating cell nuclear antigen (PCNA), and rabbit IgG anti bodies from Santa Cruz Biotech (Delaware, CA, USA); anti-P450scc antibody from Chemicon (Temecula, CA, USA); and anti-StAR and anti-LH (luteinizing hormone) anti bodies from Abcam (Cambridge, UK). Animals and BPA exposure. Adult female Sprague-Dawley rats [8 weeks of age, 200-250 g body weight (BW)

Bisphenol A: an emerging threat to female fertility

“…Conversely, in further studies conducted on female adult mice and rats treated with low BPA doses by oral and gavage administration, no changes in circulating E2 levels have been reported during proestrus and diestrus [87,88]. Moreover, in female adult rats exposed in adulthood to low BPA doses by gavage administration decreased circulating E2 levels have been found during estrus [30]; the decrease in circulating E2 levels in female adult rats exposed to low BPA doses have been associated to a down-regulation of StAR and aromatase protein synthesis, as confirmed by immunohistochemical studies on ovary [30]. In female adult rats postnatally exposed to subcutaneous administration of low and high BPA doses an increase of circulating T levels and a decrease of circulating P levels has been detected in adulthood [80].…”

“…Oral administration of low BPA doses in female adult mice and rats increased serum FSH and LH levels during proestrus [78,86], while increased only serum LH levels during proestrus when exposed to subcutaneous administration of low BPA doses [78]. Moreover, female adult rats exposed to gavage of low BPA doses showed increased serum LH levels and LH protein content in the pituitary gland, with no change in FSH levels and FSH protein content, during estrus [30]. In rat female offspring perinatally and postnatally exposed, from GD 1 to PND21, to oral administration of low BPA doses increased serum LH levels were observed during prepubertal period [31], while higher BPA doses, although still in the range of low doses, precluded the production of an E2-induced LH surge, during estrus, in rat female pups postnatally exposed, from PND1 to PND7, by subcutaneous administration [82].…”

“…Several experimental in vivo studies have investigated the effects of BPA exposure on HPO axis regulation [29][30][31][78][79][80][81][82][83][84][85][86][87][88][89][90].…”

“…Moreover, BPA is also able to inhibit androgen function by binding AR [27]. Particularly, BPA is able to influence ovarian morphology [6] and function, especially steroidogenesis [28][29][30][31][32][33][34] and folliculogenesis [32,[34][35][36], and, as well as uterine morphology [37] and function, especially uterine receptivity, consisting of the uterine ability to accommodate embryo attachment [38][39][40], and embryo implantation [37][38][39][40]. The impairment of endocrine function, and the consequent impairment of ovarian and uterine morphology and function, may lead to the development of several diseases involving reproductive system, especially ovary and uterus [19,41,42].…”

Differentiation of PC12 cells expressing estrogen receptor alpha: A new bioassay for endocrine-disrupting chemicals evaluation

“…are generally defined as estrogenic compounds. Concentration of BPA was found in several biological samples such as blood, milk and urine (Lee et al, 2013). BPA mimics E2 in numerous in vivo and in vitro studies in a concentration range of 10 -9 M to 10 -5 M. For example, BPA induced cell proliferation in the uterus of ovariectomized rats in vivo,and its effects were nearly identical to those induced by E2 (Steinmetz et al, 1998).…”