Bisphenol (BP) A is a common manufacturing chemical in polycarbonate plastics and has been widely used in plastics, epoxy resin liners of canned foods, dental materials, and thermal receipts. Human exposure to BPA is associated with a negative impact on human health including the development and function of the reproductive system due to its action as an endocrine-disrupting chemical (EDC). Numerous experimental studies have demonstrated that BPA impairs both male and female reproductive function, despite the variation in study paradigms such as dose, exposure route, timing, and outcomes measured. Due to the toxicological effects of BPA, BPA analogues such as BPS have been used as alternatives for BPA. However, recent evidence has suggested these BPA analogues can induce similar or even more severe toxic effects as BPA, and health risks of exposure to replacement bisphenols need to be considered. Therefore, my study was designed to examine whether prenatal exposure to BPE and BPS negatively impacts on male and female reproductive function in mice. Pregnant females were orally administrated corn oil (control), BPA, BPE, and BPS (0.5, 20, or 50mg/kg/day) from gestational day 11 (the presence of vaginal plug=1) to birth, and reproductive tissues in F1 mice were collected and analyzed in both neonatal and adult mice. In males, I observed reduced sperm counts and quality, disrupted stages of spermatogenesis in adults and increased germ cell apoptosis in neonatal testis following prenatal BPA, BPE or BPS exposure. Particularly, I found the expression of methyltransferases for DNA methylation and histone modification was also affected by prenatal exposure to BPA, BPE, or BPS in neonatal testis, suggesting a potential of epigenetic alterations in F1 males. In females, prenatal exposure to BPE and BPS accelerated the onset of puberty, disrupted estrous cyclicity, and caused several fertility problems especially in aged mice. In the neonatal ovaries, I also observed that BPE and BPS inhibit germ cell nest breakdown comparable to BPA. These results suggest that prenatal exposure to BPE and BPS with physiologically relevant doses affects male and female reproductive function probably due to germ cell development defects in the developing gonads. Finally, to understand their complete impact on male and female fertility, a study of transgenerational effects of BPE and BPS is performed to examine the transgenerational effects of prenatal exposure to BPA, BPE and BPS on reproductive function in F3 offspring. To be called transgenerational, expression of the specific phenotype will be continued at least across three generations. As described in previous studies, the direct exposure of a pregnant female (F0 generation) results in the exposure of the embryos (F1 generation) and the germline that will generate the next generation (F2 generation). Thus, I orally exposed to control treatment (corn oil), BPA, BPE or BPS (0.5 or 50 μg/kg/day) from gestational day 7 to birth in pregnant females (F0). Mice from F1 and F2 offspring were used to generate the F3 generation. In F3 males, prenatal exposure to BPA, BPE, and BPS induces persistence and even more severe phenotypes in sperm counts and motility in the F3 generation than in the F1 offspring. The expression of DNA and histone methyltransferases were transgenerationally increased by BPA, BPE and BPS exposure in both neonatal and adult testis. In F3 females, prenatal exposure to BPA, BPE, and BPS accelerated the onset of puberty and exhibited abnormal estrous cyclicity, and those females exhibited similar fertility problems as those in the F1 generation. However, BPA, BPE and BPS exposure did not affect neonatal follicular development such as germ cell nest breakdown or follicle numbers in the ovary on postnatal day 4. Taken together, our results suggest that prenatal exposure to BPA analogues, BPE and BPS, have transgenerational effects on male and female reproductive function in mice. Our findings suggest the hypothesis that transgenerational epigenetic alterations in germ cells may lead to reproductive disorders/dysfunction in the F3 generation.

Bisphenol A (BPA) is one of the highest volume chemicals produced worldwide and, as a result, is universally found in environmental and human matrixes. Bisphenol A is a known endocrine disruptor that acts as an estrogen agonist and an androgen antagonist. Due to health concerns, BPA is being phased out and replaced by other bisphenol analogues structurally similar to BPA. To date, there have been little to no studies showing the effects of BP analogues on the reproductive organ development of male mice. Thus, this study aimed to compare the effects of BPA and selected analogues (including BPB, BPE, and BPS) on the reproductive organ development in male mice, and determine preliminary toxicity threshold levels, such as the lowest-observed-effect-dose (LOED) and no-observed-effect-dose (NOED). Exposure to BPA, BPB and BPE via subcutaneous injection at a dose of 10 μg/g body weight (bw)/day each significantly caused a decrease in anogenital distance and glans penis length in male mice. Testis weight was also significantly reduced by BPA and BPE. Although BPS did not cause an effect on the glans penis length, anogenital distance or testis weight, histology work indicated that the spines on the glans penis were at a different developmental stage than the control. A similar result was seen with BPA on the glans penis spines. The LOED and NOED of BPA affecting anogenital distance, penis length, or testis weight were determined to be 10 and 5 μg/g bw/day, respectively. These LOED and NOED values are preliminary for BPA, because only five dose levels are used. Further research is needed to estimate more accurate threshold levels for the studied endpoints for BPA as well as other bisphenol analogues. The results indicated that some bisphenol analogues (BPB and BPE) showed comparable effects to BPA on the reproductive organ development of male mice, including anogenital distance and penis length. This could be indicative of more severe reproductive issues later in life and raised a concern on the safety of using these analogues to replace BPA in consumer products. More research is needed to investigate the mechanisms of the observed effects on genetic or molecular levels, determine what the long-term adverse effects of bisphenol analogues are to the reproductive system of male mice, and determine whether similar effects will be seen at dose levels comparable to human exposure rates.

No description available.

No description available.

Bisphenol A is a widely used chemical in the manufacture of plastics. The presence of BPA in the environment adversely affects human health due to contamination of air, drinking water and food. Growing concerns about the effects of BPA have led to its regulation in production and development of alternative chemicals to BPA, such as bisphenol S (BPS). However, the effects of BPS were not properly tested before its introduction to production and the effects on human reproduction are still unknown. For this reason, it is desirable to test the effect of BPS on mammalian oocyte development. This study hypothesizes that BPS exposure causes inhibition of meiotic maturation of porcine oocytes in vitro. This study aims to investigate the potency of BPS at low concentrations corresponding to normal human exposures to selected porcine oocyte proteins. The results of this study demonstrate the negative effect of BPS on the progression of meiotic maturation and reaching the mature oocyte stage. In addition, the results show an increase in the formation of defective meiotic spindles and a disruption of mitochondrial integrity after exposure to BPS concentrations. However, the effect of BPS on double-strand breaks was not demonstrated in this study, in contrast to the case of BPA. Taken together, the results show...

Thousands of synthetic chemicals have been released into the environment, causing widespread exposures of wildlife and humans alike. Some of these chemicals are known to disrupt aspects of hormone action thus inducing abnormalities in endocrine tissues and organs. Bisphenol S (BPS) and tetrabromobisphenol A (TBBPA), two largely unstudied chemicals commonly used in consumer products, are suspected to have endocrine disrupting properties based on their similar chemical structures to known endocrine disrupting chemicals (EDCs). To determine whether developmental exposure to BPS or TBBPA induced abnormalities in the ovary, mice were administered oil, BPS or TBBPA during pregnancy and lactation. The ovaries of female offspring were examined for gross morphological, immunohistological and gene expression differences at postnatal day (PND) 22 and week 16. To determine whether these exposures alter responses to hormones, two females from each litter were administered either oil or ethinyl estradiol (EE2) from PND 19-21. Our study identified significant differences in ovarian follicular formation and gene expression after developmental TBBPA and BPS exposures. Most effects were observed at PND22 (pre-puberty), and were apparent after the EE2 challenge, suggesting that changes induced by BPS and TBBPA are age- and hormone- dependent. Our results are consistent with the hypothesis that TBBPA and BPS are EDCs; that these compounds can disrupt development of the ovary; and that the observed effects of TBBPA and BPS exposure are similar to risk factors for ovarian diseases including cancer. These findings may indicate that widespread exposures to BPS and TBBPA could have implications for public health.

No description available.

Humans experience ubiquitous exposures to estrogenic environmental chemicals from food, personal care products, and other industrial and consumer goods. Bisphenol A (BPA), a well-studied xenoestrogen, is known to alter development of estrogen-sensitive organs including the brain, reproductive tract, and mammary gland. Bisphenol S (BPS), which has a similar chemical structure to BPA, is also used in many consumer products, but its effects on estrogen-sensitive organs in mammals has not been thoroughly examined. In our study, pregnant CD-1 mice were orally exposed to BPS or ethinyl estradiol (EE2, a positive control for estrogenicity) from gestational day 9 through postnatal day (PND) 2, the period when many estrogen-sensitive organs are developing. After weaning, the offspring were administered either oil (vehicle) or an estrogen challenge (1 μg EE2/kg/day) for ten days starting at PND21 (prior to puberty), PND80 (early adulthood), or PND260 (later adulthood). Timing of puberty was evaluated in females by noting the date on which vaginal opening occurred. After the 10 day estrogen challenge, we evaluated the response of endocrine sensitive organs through measurements of organ weight, tissue morphology, and gene expression in both males and females. We observed dose- and sex-specific effects of BPS and EE2 treatment, as well as alterations in the responses of males and females to the estrogen challenge. This study sheds light on the effects of low dose xenoestrogen exposures on estrogen-sensitive organs including the reproductive tract and mammary gland. Furthermore, it improves our understanding of the influence of environmental chemicals on secular trends of earlier age of puberty in girls reported over the past few decades.

Bisphenol S (BPS) is an industrial chemical used in the process of polymerization of polycarbonate plastics and epoxy resins and thus can be found in various plastic products and thermal papers. The microbiota disrupting effect of BPS on the community structure of the microbiome has already been reported, but little is known on how BPS affects bacterial activity and function. To analyze these effects, we cultivated the simplified human intestinal microbiota (SIHUMIx) in bioreactors at a concentration of 45 µM BPS. By determining biomass, growth of SIHUMIx was followed but no differences during BPS exposure were observed. To validate if the membrane composition was affected, fatty acid methyl esters (FAMEs) profiles were compared. Changes in the individual membrane fatty acid composition could not been described; however, the saturation level of the membranes slightly increased during BPS exposure. By applying targeted metabolomics to quantify short-chain fatty acids (SCFA), it was shown that the activity of SIHUMIx was unaffected. Metaproteomics revealed temporal effect on the community structure and function, showing that BPS has minor effects on the structure or functionality of SIHUMIx.

No description available.