During the first 2 wk of gestation in rats, gonadotropin levels are low [52, 53] and the cyclic phase of folliculogenesis is silenced, to resume during the last week of gestation concomitant with a rise in FSH in preparation for a postpartum estrus [5254]

During the first 2 wk of gestation in rats, gonadotropin levels are low [52, 53] and the cyclic phase of folliculogenesis is silenced, to resume during the last week of gestation concomitant with a rise in FSH in preparation for a postpartum estrus [5254]. A significant reduction in the expression of catalase, an antioxidant enzyme, and downregulation of the expression of insulin-like factor 3 (Insl3) and 17alpha-hydroxylase (Cyp17a1) were observed in the ovary. In addition , BFR exposure affected steroidogenesis; we observed a significant decrease in circulating 17-hydroxypregnenolone and an increase in testosterone concentrations in BFR-exposed dams. Thus, BFRs target ovarian function in the rat, adversely affecting both folliculogenesis and steroidogenesis. Keywords: androgens, brominated flame retardants, catalase, endocrine disrupters, folliculogenesis, HBCDD, insulin-like factor 3, ovary, oxidative stress, PBDE, steroidogenesis, toxicology == INTRODUCTION == Flame retardant chemicals are produced in high volumes, widespread in the environment, and detected in each of us, and they bioaccumulate [1]. These chemicals are incorporated into numerous products that typically are highly flammable, such as plastics, textiles, and foams; they contribute up to 30% of the weight of the components in office and home electronics, synthetic building materials, and furniture or motor vehicles [1]. A major class of flame retardants is represented by brominated flame retardants (BFRs), including A-1165442 polybrominated A-1165442 diphenyl ethers (PBDEs) and hexabromocyclododecane (HBCDD) [1]. With time, these flame retardants leach out into domestic environments, resulting in repetitive exposure through inhalation and ingestion [2, 3]. Because the BFRs are lipophilic and persistent [4], they bioaccumulate in human breast milk, serum, and corpulence tissues [5] and biomagnify through food chains [3]. A number of the PBDEs that have been banned in North America for more than 10 years are still detected in human body fluids as well as in domestic dust [6, 7]. Evidence is increasing that the BFRs are endocrine disruptors, affecting androgenic, estrogenic, and thyroid hormone activities [8]. In humans, adverse effects on male reproduction are associated with exposure to BFRs and include changes A-1165442 in the levels of steroid hormones [911] and a decrease in sperm count and quality [1214]. In utero and lactational exposure to PBDEs is associated with an increased incidence of cryptorchidism [15, 16]. In adolescent girls, high serum levels of BFRs are associated with an earlier age of menarche [1719]. Previous investigations have reported that the detection of A-1165442 high levels of PBDEs in follicular fluid or in serum is associated with a longer time to conceive [20] and with failure of embryo implantation after in vitro fertilization [21]. Most studies on the effects of the BFRs in pet models have focused on the consequences of exposure to individual congeners or commercial mixtures. These studies show that BFRs disrupt the endocrine system [8, 22] and are associated with diabetes, cancer, and neurobehavioral and developmental disorders [23]. The window of exposure is important because perinatal exposure to BFRs results in clear disruptions in the timing of puberty and in gametogenesis in male and female rats [2427]. One of the difficulties in relating the animal experiments to human health is that human exposure is to the complex mixtures of BFRs found in the environment rather than to specific, individual congeners. We have shown that chronic exposure of adult male rats to an environmentally relevant BFR mixture, mimicking the relative congener levels in house dust, resulted in an enlargement of the liver and kidney and altered thyroid hormone parameters in the absence of effects on the reproductive system [28]. No changes in estrous cyclicity or pregnancy outcomes, such as mating and fecundity indices or numbers of live fetuses, are observed in female rats fed this same BFR mixture before mating and during gestation [29]. However , in vitro studies with porcine antral follicles have shown that steroid hormone production and the expression of steroidogenic enzymes are affected by single PBDE congeners [30], their metabolites [31], or a mixture reflecting the PBDEs detected in human serum [32]. There may be multiple explanations for a divergence in findings in epidemiological studies, in festn animal experiments, and in vitro studies. One possibility is that species differences exist; however , the BFRs have similar endocrine-disrupting activities in a wide range of species [8]. A second possibility is that the standard testing procedures to assess the effects of such chemicals on female reproduction may not detect important effects on ovarian function. The objective of the present study is to determine whether BFRs target the ovary in the rat. To accomplish this goal, ovarian function was assessed in female Sprague-Dawley rats fed an environmentally relevant BFR mixture before mating and during gestation in IGFBP6 which no significant changes in estrous cyclicity, mating, or fecundity were observed [29]. == MATERIALS AND METHODS ==.