Bisphenol AF blocks Leydig cell regeneration from stem cells in male rats.
Bisphenol AF blocks Leydig cell regeneration from stem cells in male rats.
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DOI：
10.1016/j.envpol.2022.118825
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发表时间：
2022-01
影响因子：
8.9
通讯作者：
Yige Yu;Xiu Xin;Feifei Ma;Xiaoheng Li;Yiyan Wang;Qiqi Zhu;Haiqiong Chen;Huitao Li;R. Ge
中科院分区：
文献类型：
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作者：
Yige Yu;Xiu Xin;Feifei Ma;Xiaoheng Li;Yiyan Wang;Qiqi Zhu;Haiqiong Chen;Huitao Li;R. Ge
双酚A（BPA）是一种普遍存在的环境污染物，主要来自塑料的生产和使用。双酚A的使用受到限制，新的双酚A类似物（包括双酚AF，BPAF）正在被生产出来以取代它，但BPAF对男性生殖系统的影响尚不清楚。在这里，我们报告BPAF对大鼠睾丸间质细胞再生的影响。通过乙烷二甲烷磺酸盐（EDS，i. p.，75 mg/kg）处理后14 d开始再生。在EDS后第7-28天，我们对大鼠灌胃0、10、100和200 mg/kg BPAF。BPAF显著降低血清睾酮和孕酮水平在10 mg/kg。在100和200 mg/kg剂量下，它显著降低了雌二醇、促黄体生成素和促卵泡激素的血清水平。BPAF在200 mg/kg时显著减少Leydig细胞数量。BPAF在10 mg/kg及以上剂量组显著下调Leydig细胞Cyp 17 a1的表达，100和200 mg/kg剂量组显著下调Insl 3、星星、Hsd 17 b3、Hsd 11 b1的表达，200 mg/kg剂量组显著上调Sertoli细胞Fshr、Dhh和Sox 9的表达。200 mg/kg的BPAF诱导氧化应激并降低SOD 2水平。在100和200 mg/kg剂量下，它通过增加BAX、LC 3B和BECLIN 1的水平并降低BCL 2和p62的水平来诱导细胞凋亡和自噬。可能通过降低AKT 1和mTOR的磷酸化水平诱导自噬。BPAF在10 μM浓度下还显着诱导大鼠R2 C Leydig细胞的活性氧产生和细胞凋亡，并在10 μ M浓度下减少大鼠R2 C Leydig细胞的睾酮合成，但处理24小时后不影响细胞活力。总之，BPAF是一种新的内分泌干扰物，抑制Leydig细胞的再生。
Bisphenol A (BPA) is a ubiquitous environmental pollutant, mainly from the manufacture and use of plastics. The use of BPA is restricted, and its new analogs (including bisphenol AF, BPAF) are being produced to replace it. However, the effect of BPAF on the male reproductive system remains unclear. Here, we report the effect of BPAF on Leydig cell regeneration in rats. Leydig cells were eliminated by ethane dimethane sulfonate (EDS, i.p., 75 mg/kg) and the regeneration began 14 days after its treatment. We gavaged 0, 10, 100, and 200 mg/kg BPAF to rats on post-EDS day 7–28. BPAF significantly reduced serum testosterone and progesterone levels at ≧10 mg/kg. It markedly reduced serum levels of estradiol, luteinizing hormone, and follicle-stimulating hormone at 100 and 200 mg/kg. BPAF significantly reduced Leydig cell number at 200 mg/kg. BPAF significantly down-regulated the expression ofCyp17a1at doses of 10 mg/kg and higher and the expression ofInsl3,Star,Hsd17b3,Hsd11b1in Leydig cells at 100 and 200 mg/kg, while it induced a significant up-regulation ofFshr,Dhh, andSox9in Sertoli cells at 200 mg/kg. BPAF induced oxidative stress and reduced the level of SOD2 at 200 mg/kg. It induced apoptosis and autophagy by increasing the levels of BAX, LC3B, and BECLIN1 and lowering the levels of BCL2 and p62 at 100 and 200 mg/kg. It induced autophagy possibly via decreasing the phosphorylation of AKT1 and mTOR. BPAF also significantly induced ROS production and apoptosis at a concentration of 10 μM, and reduced testosterone synthesis in rat R2C Leydig cells at a concentration of 10 μMin vitro, but did not affect cell viability after 24 h of treatment. In conclusion, BPAF is a novel endocrine disruptor, inhibiting the regeneration of Leydig cells.