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Paternal Exposure to Bisphenol-A Transgenerationally Impairs Testis Morphology, Germ Cell Associations, and Stemness Properties of Mouse Spermatogonial Stem Cells.

ABSTRACT: Bisphenol-A (BPA) exposure in an adult male can affect the reproductive system, which may also adversely affect the next generation. However, there is a lack of comprehensive data on the BPA-induced disruption of the association and functional characteristics of the testicular germ cells, which the present study sought to investigate. Adult male mice were administered BPA doses by gavage for six consecutive weeks and allowed to breed, producing generations F1-F4. Testis samples from each generation were evaluated for several parameters, including abnormal structure, alterations in germ cell proportions, apoptosis, and loss of functional properties of spermatogonial stem cells (SSCs). We observed that at the lowest-observed-adverse-effect level (LOAEL) dose, the testicular abnormalities and alterations in seminiferous epithelium staging persisted in F0-F2 generations, although a reduced total spermatogonia count was found only in F0. However, abnormalities in the proportions of germ cells were observed until F2. Exposure of the male mice (F0) to BPA alters the morphology of the testis along with the association of germ cells and stemness properties of SSCs, with the effects persisting up to F2. Therefore, we conclude that BPA induces physiological and functional disruption in male germ cells, which may lead to reproductive health issues in the next generation.

SUBMITTER: Karmakar PC

PROVIDER: S-EPMC7432732 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Paternal Exposure to Bisphenol-A Transgenerationally Impairs Testis Morphology, Germ Cell Associations, and Stemness Properties of Mouse Spermatogonial Stem Cells.

Karmakar Polash Chandra PC Ahn Jin Seop JS Kim Yong-Hee YH Jung Sang-Eun SE Kim Bang-Jin BJ Lee Hee-Seok HS Kim Sun-Uk SU Rahman Md Saidur MS Pang Myung-Geol MG Ryu Buom-Yong BY

International journal of molecular sciences 20200729 15

Bisphenol-A (BPA) exposure in an adult male can affect the reproductive system, which may also adversely affect the next generation. However, there is a lack of comprehensive data on the BPA-induced disruption of the association and functional characteristics of the testicular germ cells, which the present study sought to investigate. Adult male mice were administered BPA doses by gavage for six consecutive weeks and allowed to breed, producing generations F1-F4. Testis samples from each generat ...[more]

PMID: 32751382

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Project description:BackgroundUsing an organotypic culture system termed human Fetal Testis Assay (hFeTA) we previously showed that 0.01 μM BPA decreases basal, but not LH-stimulated, testosterone secreted by the first trimester human fetal testis. The present study was conducted to determine the potential for a long-term antiandrogenic effect of BPA using a xenograft model, and also to study the effect of BPA on germ cell development using both the hFETA and xenograft models.MethodsUsing the hFeTA system, first trimester testes were cultured for 3 days with 0.01 to 10 μM BPA. For xenografts, adult castrate male nude mice were injected with hCG and grafted with first trimester testes. Host mice received 10 μM BPA (~ 500 μg/kg/day) in their drinking water for 5 weeks. Plasma levels of total and unconjugated BPA were 0.10 μM and 0.038 μM respectively. Mice grafted with second trimester testes received 0.5 and 50 μg/kg/day BPA by oral gavage for 5 weeks.ResultsWith first trimester human testes, using the hFeTA model, 10 μM BPA increased germ cell apoptosis. In xenografts, germ cell density was also reduced by BPA exposure. Importantly, BPA exposure significantly decreased the percentage of germ cells expressing the pluripotency marker AP-2γ, whilst the percentage of those expressing the pre-spermatogonial marker MAGE-A4 significantly increased. BPA exposure did not affect hCG-stimulated androgen production in first and second trimester xenografts as evaluated by both plasma testosterone level and seminal vesicle weight in host mice.ConclusionsExposure to BPA at environmentally relevant concentrations impairs germ cell development in first trimester human fetal testis, whilst gonadotrophin-stimulated testosterone production was unaffected in both first and second trimester testis. Studies using first trimester human fetal testis demonstrate the complementarity of the FeTA and xenograft models for determining the respective short-term and long term effects of environmental exposures.

Dataset Information

Paternal Exposure to Bisphenol-A Transgenerationally Impairs Testis Morphology, Germ Cell Associations, and Stemness Properties of Mouse Spermatogonial Stem Cells.

Publications

Paternal Exposure to Bisphenol-A Transgenerationally Impairs Testis Morphology, Germ Cell Associations, and Stemness Properties of Mouse Spermatogonial Stem Cells.

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