Gestational Exposure to Bisphenol A Affects Testicular Morphology, Germ Cell Associations, and Functions of Spermatogonial Stem Cells in Male Offspring.

Polash Chandra Karmakar,Hee-Seok Lee,Sang-Eun Jung,Jin Seop Ahn,Yong-Hee Kim,Buom-Yong Ryu,Bang-Jin Kim

doi:10.3390/ijms21228644

Polash Chandra Karmakar, Hee-Seok Lee + Show 5 more

Open Access

https://doi.org/10.3390/ijms21228644

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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.

Highlights

Bisphenol A (2,2-bis(4-hydroxyphenyl)propane; bisphenol A (BPA)) is a ubiquitous endocrine disruptor (ED) with widespread industrial applications, especially to make plastics and epoxy resins used by consumers [1,2]
As BPA has the ability to promote several diseases and health hazards, this xenoestrogenic compound has become a crucial topic of research over the last 50 years
Some studies have reported the vicious effects of BPA on reproduction and sexual dysfunction in males and females upon exposure in childhood or even in adulthood [38,39,40]

Summary

Introduction

Bisphenol A (2,2-bis(4-hydroxyphenyl)propane; BPA) is a ubiquitous endocrine disruptor (ED) with widespread industrial applications, especially to make plastics and epoxy resins used by consumers [1,2]. Previous studies have established that BPA has estrogenic and anti-androgenic properties both in vivo and in vitro [7,8]. BPA is a xenoestrogenic compound that possibly hinders hormonal signals by reacting with estrogen receptors on testicular germ cells [17]. BPA-related in vitro effects on the characteristics of spermatozoa [18], low sperm count [19], increased DNA damage in sperm [20], and protein alteration in sperm [21] have been studied well. Other studies demonstrating BPA-related disruption in the meiotic process [22] and reduction in the crossover of chromosomes [23] have been conducted. BPA-induced effects on oxidative stress [24] and DNA methylation [25] have been proven. Laws have been made that define ranges for BPA exposure: tolerable daily intake (TDI; 50 μg/kg body weight (bw)/day), no-observed-adverse-effect-level (NOAEL; 5 mg/kg bw/day), and lowest-observed-adverse-effect level (LOAEL; 50 mg/kg bw/day) [26,27]

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