Background

Bisphenol A (BPA) is a well-known endocrine disruptor that affects male fertility. However, the main biological events through which BPA affects spermatogenesis remain to be identified.

Methods

Adult male mice were treated by feeding with drinking water containing BPA (0.2 μg/ml, 20 μg/ml, 200 μg/ml, respectively) for two months. Testes were collected for protein extraction or for immunohistochemical analysis. Epididymal spermatozoa were collected for sperm quality evaluation and male fertility assay by in vitro fertility (IVF). Serums were collected for detection of testosterone levels. Proteins associated with germ cell proliferation, meiosis, blood-testis barrier, and steroidogenesis production were examined in BPA-treated and control mice testes. CCK8 assay was used to detect the effect of BPA on the proliferation of GC-1 and GC-2 cells.

Results

The BPA-treated mice were characterized by decreased sperm quality, serum testosterone levels and, sub-fertile phenotype characterizing with low pregnancy rates and reduced fertilization efficiency. In lower BPA (0.2 μg/ml) treatment, PCNA and PLZF were down-expressed that indicated impaired germ cell proliferation. SYCP3 was down-expressed in BPA-treated mice, but expressions of other proteins associated with meiosis and blood-testis barrier were not significantly altered. CYP11A1 and HSD3B1 were down-expressed in BPA-treated mice that demonstrated reduced steroidogenesis activity. BPA has a concentration-dependent inhibition effect on the proliferation of GC-1 and GC-2 cells. Conclusively, low doses BPA exposure reduced mice sperm quality mainly by impairing germ cell proliferation, leading to reduced male fertility. The study would provide relevant information for investigation on molecular mechanisms and protective strategy on male production.

中文翻译：

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BPA的长期暴露会损害雄性生殖细胞的增殖，并导致雄性小鼠的精子质量降低。

背景

双酚A（BPA）是一种众所周知的内分泌干扰物，会影响男性的生育能力。然而，BPA通过其影响精子发生的主要生物学事件仍有待确定。

方法

成年雄性小鼠接受含BPA（分别为0.2μg/ ml，20μg/ ml，200μg/ ml）的饮用水喂养两个月。收集睾丸用于蛋白质提取或用于免疫组织化学分析。收集附睾精子用于精子质量评估和通过体外受精（IVF）进行雄性受精测定。收集血清以检测睾丸激素水平。在BPA处理和对照小鼠的睾丸中检查了与生殖细胞增殖，减数分裂，血液睾丸屏障和类固醇生成相关的蛋白质。CCK8法用于检测双酚A对GC-1和GC-2细胞增殖的影响。

结果

用BPA治疗的小鼠的特征是精子质量下降，血清睾丸激素水平下降，亚可育表型，低妊娠率和受精效率降低。在较低的BPA（0.2μg/ ml）处理中，PCNA和PLZF的表达降低，表明生殖细胞增殖受损。SYCP3在BPA治疗的小鼠中表达降低，但与减数分裂和血液-睾丸屏障相关的其他蛋白的表达没有明显改变。CYP11A1和HSD3B1在BPA治疗的小鼠中表达降低，表明类固醇生成活性降低。BPA对GC-1和GC-2细胞的增殖具有浓度依赖性的抑制作用。总之，低剂量的BPA暴露主要是通过削弱生殖细胞增殖来降低小鼠的精子质量，从而导致雄性生育力降低。