Effects of perfluorooctanoic acid on stem Leydig cell functions in the rat

Effects of perfluorooctanoic acid on stem Leydig cell functions in the rat
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全氟辛酸对大鼠干间质细胞功能的影响

DOI:
10.1016/j.envpol.2019.03.120
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发表时间:
2019-07-01
影响因子:
8.9
通讯作者:
Ye, Leping
Ye, Leping
中科院分区:
环境科学与生态学2区
文献类型:
--
作者:
Lu, Hemin;Zhang, Huishan;Ye, Leping

文献摘要

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全氟辛酸(PFOA)和全氟辛烷磺酸(PFOS)是广泛存在于环境中的两种全氟化学品。有证据表明,PFOA可能与大鼠和人类的雄性生殖功能障碍有关。PFOA暴露抑制Leydig细胞的功能。然而,PFOA是否影响干Leydig细胞(SLC)仍然是未知的。在本研究中,我们研究了短期暴露于PFOA对Leydig细胞再生的影响,并探讨了可能的机制。将36只成年SD大鼠随机分为3组,分别腹腔注射75 mg/kg乙烷二甲基磺酸钠(EDS)清除睾丸间质细胞。从EDS后第7天开始,3组大鼠连续9天接受0、25或50 mg/kg/天的PFOA(每组n = 12)。暴露于PFOA显着降低血清睾酮水平的第21天和第56天后EDS治疗。Leydig细胞特异性基因(Lhcgr、Scarb 1、星星、Cyp 11 a1、Hsd 3b 1、Hsd 11 b1和Cyp 17 a1)的表达水平和蛋白水平均下调。PFOA暴露也可能影响SLC或其后代的增殖,因为EDS后第21天PCNA阳性Leydig细胞的数量减少。这些体内观察结果也得到了体外研究的证实,在体外研究中,通过培养生精小管测试了全氟辛酸的影响。总之,PFOA暴露可能通过影响SLC或其后代的增殖和分化来抑制Leydig细胞的发育。(C)2019爱思唯尔有限公司版权所有。
Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic (PFOS) are two perfluorinated chemical products widely existing in the environment. Evidence suggested that PFOA might relate to male reproductive dysfunction in rats and humans. PFOA exposure inhibited the function of Leydig cells. However, it is still unknown whether PFOA affects stem Leydig cells (SLCs). In the present study, we examined the effects of a short-term exposure to PFOA on Leydig cell regeneration and also explored the possible mechanism involved. Thirty-six adult Sprague-Dawley rats were randomly divided into three groups and intraperitoneally injected with a single dose of 75 mg/kg ethane dimethyl sulfonate (EDS) to eliminate all Leydig cells. From post-EDS day 7, the 3 group rats received 0, 25 or 50 mg/kg/day PFOA (n = 12 per group) for 9 consecutive days. Exposure to PFOA significantly decreased serum testosterone levels by day 21 and day 56 post-EDS treatment. Also, the expression levels of Leydig cell specific genes (Lhcgr, Scarb1, Star, Cyp11a1, Hsd3b1, Hsd11b1 and Cyp17a1) and their protein levels were all downregulated. PFOA exposure may also affect proliferation of SLCs or their progeny since the numbers of PCNA-positive Leydig cells were reduced by post-EDS day 21. These in vivo observations were also confirmed by in vitro studies where the effects of PFOA were tested by culture of seminiferous tubules. In summary, PFOA exposure inhibits the development of Leydig cells, possibly by affecting both the proliferation and differentiation of SLCs or their progeny. (C) 2019 Elsevier Ltd. All rights reserved.