Xie Meina, Bu Pengli, Li Fengjie, Lan Shijian, Wu Hongjuan, Yuan Lu, Wang Ying
Medicine Experiment Center, Weifang Medical University, Wei Fang 261053, P. R. China.
School of Bioscience and Technology, Weifang Medical University, Wei Fang 261053, P. R. China.
Oncotarget. 2016 Mar 1;7(9):10606-15. doi: 10.18632/oncotarget.7218.
Bisphenol A (BPA) is a widely used industrial plasticizer, which is ubiquitously present in the environment and organisms. As an endocrine disruptor, BPA has caused significant concerns regarding its interference with reproductive function. However, little is known about the impact of BPA exposure on early testicular development. The aim of the present study was to investigate the influence of neonatal BPA exposure on the first wave of spermatogenesis. Newborn male mice were subcutaneously injected with BPA (0.01, 0.1 and 5 mg/kg body weight) daily from postnatal day (PND) 1 to 21. Histological analysis of testes at PND 22 revealed that BPA-treated testes contained mostly spermatogonia and spermatocytes with markedly less round spermatids, indicating signs of meiotic arrest. Terminal dUTP nick-end labeling (TUNEL) assay showed that BPA treatment significantly increased the number of apoptotic germ cells per tubule, which corroborated the observation of meiotic arrest. In addition, BPA caused abnormal proliferation of germ cells as revealed by Proliferating Cell Nuclear Antigen (PCNA) immunohistochemical staining. Mechanistically, BPA-treated testes displayed a complete lack of BOULE expression, which is a conserved key regulator for spermatogenesis. Moreover, BPA significantly increased the expression of estrogen receptor (ER) α and β in the developing testis. The present study demonstrated that neonatal BPA exposure disrupted meiosis progression during the first wave of spermatogenesis, which may be, at least in part, due to inhibition of BOULE expression and/or up-regulation of ERα/β expression in BPA-exposed developing testis.
双酚A（BPA）是一种广泛使用的工业增塑剂，在环境和生物体内普遍存在。作为一种内分泌干扰物，BPA对生殖功能的干扰引起了人们的极大关注。然而，关于BPA暴露对早期睾丸发育的影响知之甚少。本研究的目的是探讨新生小鼠暴露于BPA对第一波精子发生的影响。从出生后第1天（PND）至21天，每天给新生雄性小鼠皮下注射BPA（0.01、0.1和5mg/kg体重）。对PND 22的睾丸进行组织学分析发现，经BPA处理的睾丸主要含有精原细胞和精母细胞，圆形精子细胞明显较少，表明存在减数分裂停滞的迹象。末端脱氧核苷酸转移酶介导的缺口末端标记（TUNEL）分析表明，BPA处理显著增加了每个曲细精管中凋亡生殖细胞的数量，这证实了减数分裂停滞的观察结果。此外，增殖细胞核抗原（PCNA）免疫组化染色显示，BPA导致生殖细胞异常增殖。从机制上讲，经BPA处理的睾丸完全缺乏BOULE表达，而BOULE是精子发生的一个保守关键调节因子。此外，BPA显著增加了发育中睾丸中雌激素受体（ER）α和β的表达。本研究表明，新生小鼠暴露于BPA会破坏第一波精子发生过程中的减数分裂进程，这可能至少部分是由于BPA暴露的发育中睾丸中BOULE表达受到抑制和/或ERα/β表达上调所致。
