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.
Highlights
Bisphenol-A (2,2-bis(4-hydroxyphenyl)propane; BPA) is one of the most commonly used endocrine disruptors worldwide, with widespread industrial applications in the manufacture of plastics and epoxy resins [1,2]
We investigated the transgenerational effects of BPA exposure on the physiology, health, and stemness characteristics of testicular germ cells, and testicular morphology in adult mice
With the relatively long period of exposure in adult age, we anticipated that the effects would be prevalent mostly in F0 generation, with the possibility of transgenerational transmission
Summary
Bisphenol-A (2,2-bis(4-hydroxyphenyl)propane; BPA) is one of the most commonly used endocrine disruptors worldwide, with widespread industrial applications in the manufacture of plastics and epoxy resins [1,2]. It is chemically stable and has been shown to exhibit environmental persistence after leaching from BPA-enriched products at normal or elevated temperature [3,4]. BPA can exert widespread effects on several endocrine-related biological pathways and reproductive organs [11,12] and exhibit cellular toxicity toward many cell types, including male germ cells [13,14,15,16]
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