Gestational Exposure to Bisphenol A Affects Testicular Morphology,Germ Cell Associations,and Functions of Spermatogonial Stem Cells in Male Offspring |
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Authors: | Polash Chandra Karmakar Jin Seop Ahn Yong-Hee Kim Sang-Eun Jung Bang-Jin Kim Hee-Seok Lee Buom-Yong Ryu |
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Affiliation: | 1.Department of Animal Science and Technology and BET Research Institute, Chung-Ang University, Anseong 17546, Korea; (P.C.K.); (J.S.A.); (Y.-H.K.); (S.-E.J.);2.Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; ;3.Department of Food Science & Technology, Chung-Ang University, Anseong 17546, Korea; |
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Abstract: | Exposure to bisphenol A (BPA) in the gestational period damages the reproductive health of offspring; detailed evidence regarding BPA-induced damage in testicular germ cells of offspring is still limited. In this study, pregnant mice (F0) were gavaged with three BPA doses (50 μg, 5 mg, and 50 mg/kg body weight (bw)/day; tolerable daily intake (TDI), no-observed-adverse-effect-level (NOAEL), and lowest-observed-adverse-effect level (LOAEL), respectively) on embryonic days 7 to 14, followed by investigation of the transgenerational effects of such exposure in male offspring. We observed that the NOAEL- and LOAEL-exposed F1 offspring had abnormalities in anogenital distance, nipple retention, and pubertal onset (days), together with differences in seminiferous epithelial stages and testis morphology. These effects were eradicated in the next F2 and F3 generations. Moreover, there was an alteration in the ratio of germ cell population and the apoptosis rate in germ cells increased in F1 offspring at the LOAEL dose. However, the total number of spermatogonia remained unchanged. Finally, a reduction in the stemness properties of spermatogonial stem cells in F1 offspring was observed upon LOAEL exposure. Therefore, we provide evidence of BPA-induced disruption of physiology and functions in male germ cells during the gestational period. This may lead to several reproductive health issues and infertility in offspring. |
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Keywords: | bisphenol A testis morphology male germ cell apoptosis spermatogonial stem cell function |
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