Effects of gestational Perfluorooctane Sulfonate exposure on the developments of fetal and adult Leydig cells in F1 males.
Effects of gestational Perfluorooctane Sulfonate exposure on the developments of fetal and adult Leydig cells in F1 males.
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DOI：
10.1016/j.envpol.2020.114241
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发表时间：
2020-02
影响因子：
8.9
通讯作者：
Huishan Zhang;Hemin Lu;Panpan Chen;Xi-Ping Chen;Chengcheng Sun;R. Ge;Zhijian Su;Leping Ye
中科院分区：
文献类型：
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作者：
Huishan Zhang;Hemin Lu;Panpan Chen;Xi-Ping Chen;Chengcheng Sun;R. Ge;Zhijian Su;Leping Ye
研究表明，成人生活中一些最常见的男性生殖障碍可能源于胎儿。全氟辛烷磺酸(PFOS)是一种主要的环境污染物，如果在胎儿或青春期暴露，可能会影响男性生殖系统的发育。然而，胎儿期接触全氟辛烷磺酸是否会影响成人的睾丸功能仍不清楚。在此，我们研究了孕期短暂暴露于全氟辛烷磺酸对雄性后代成年间质细胞和支持细胞发育的影响。18只孕鼠随机分为3组，分别于妊娠第5~20天给予全氟辛烷磺酸0、1、5 mg/kg/d。于出生后第1、35、90天对F1雄性大鼠的睾丸功能进行评估。全氟辛烷磺酸处理显著降低了所有三个年龄组动物的血清睾酮水平。LeyDig1、Cyp11a1、CyP17a1和Hsd17b3细胞和Sertoli细胞(DHH和Sox9)多种mRNAs和蛋白的表达水平也在第1天和第90天下调。全氟辛烷磺酸暴露也可能抑制间质细胞的增殖，因为在出生后35天，增殖细胞核抗原阳性的间质细胞的数量显著减少。在间质细胞增殖和分化发生变化的同时，全氟辛烷磺酸还显著降低糖原合成酶-3β的磷酸化，而增加β-连环蛋白的磷酸化。总之，孕期全氟辛烷磺酸暴露可能对F1后代的成年睾丸功能有显著的长期影响。Wnt信号的改变可能在这一过程中发挥作用。
Studies have showed that some of the most common male reproductive disorders present in adult life might have a fetal origin. Perfluorooctane sulfonic (PFOS) is one of the major environmental pollutants that may affect the development of male reproductive system if exposed during fetal or pubertal periods. However, whether PFOS exposure during fetal period affects testicular functions in the adult is still unclear. Herein, we investigated the effects of a brief gestational exposure to PFOS on the development of adult Leydig- and Sertoli-cells in the male offspring. Eighteen pregnant Sprague-Dawley rats were randomly divided into three groups and each received 0, 1 or 5 mg/kg/day PFOS from gestational day 5–20. The testicular functions of F1 males were evaluated on day 1, 35 and 90 after birth. PFOS treatment significantly decreased serum testosterone levels of animals by all three ages examined. The expression level of multiple mRNAs and proteins of Leydig (Scarb1, Cyp11a1, Cyp17a1 and Hsd17b3) and Sertoli (Dhh and Sox9) cells were also down-regulated by day 1 and 90. PFOS exposure might also inhibit Leydig cell proliferation since the number of PCNA-positive Leydig cells were significantly reduced by postnatal day 35. Accompanied by changes in Leydig cell proliferation and differentiation, PFOS also significantly reduced phosphorylation of glycogen synthase kinase-3β while increased phosphorylation of β-catenin. In conclusion, gestational PFOS exposure may have significant long-term effects on adult testicular functions of the F1 offspring. Changes in Wnt signaling may play a role in the process.