College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China.
Biol Trace Elem Res. 2020 Jun;195(2):472-480. doi: 10.1007/s12011-019-01852-x. Epub 2019 Aug 23.
Chronic copper exposure impaired spermatogenesis in adult male mice. The aim of this study was to determine whether chronic copper exposure can induce apoptosis of testicular cell and hypospermatogenesis via disturbing testosterone synthesis in adult male mice. In the present study, sixty CD-1 male mice were randomly divided into four groups, and were continuously administered for 8 weeks by oral gavage with copper sulfate at a dose of 0, 25, 100, and 150 mg/kg/day, respectively. We determined the content of serum and testicular copper, testicular coefficient, testicular histopathology, sperm count and motility, the mRNA and protein levels of Caspase-3, Bax, and Bcl-2, Leydig cell count, testosterone content, testosterone synthetase, and testosterone synthesis-related genes. The results showed that the copper levels in serum increased in a dose-dependent manner, and the copper levels in testes were significantly related to serum copper levels. Male mice given copper sulfate 100 and 150 dosage groups showed significant decreased in sperm motility and sperm number as well as increased in testes damage, and there was no significant change in testicular coefficient in the four groups. The mRNA levels of Bcl-2 decreased and Caspase-3 increased in 150 dosage group, and Bax increased in two higher dosage groups. Meanwhile, Caspase-3 and Bax proteins increased in 150 dosage group, and Bcl-2 protein decreased in three copper treatment groups. Nevertheless, there were no differences on the levels of testosterone content and testosterone synthetase of 3β-HSD, 17β-HSD, 17α-Hyd, and 20α-Hyd, mRNA levels of Cyp11a1, Cyp17a1, and Star, and quantity of Leydig cells in four groups. Overall, these data showed that chronic copper exposure led to copper residues in the testes, and the doses of 100 and 150 mg/kg/day copper sulfate may induce hypospermatogenesis by increasing apoptosis without affecting testosterone secretion.
慢性铜暴露损害成年雄性小鼠的精子发生。本研究旨在确定慢性铜暴露是否通过干扰成年雄性小鼠的睾酮合成来诱导睾丸细胞凋亡和少精子症。在本研究中，将 60 只 CD-1 雄性小鼠随机分为 4 组，分别连续 8 周经口灌胃给予硫酸铜，剂量为 0、25、100 和 150mg/kg/天。我们测定了血清和睾丸铜含量、睾丸系数、睾丸组织病理学、精子计数和活力、Caspase-3、Bax 和 Bcl-2 的 mRNA 和蛋白水平、Leydig 细胞计数、睾酮含量、睾酮合成酶和睾酮合成相关基因。结果表明，血清铜水平呈剂量依赖性增加，睾丸铜水平与血清铜水平显著相关。给予硫酸铜 100 和 150 剂量组的雄性小鼠精子活力和精子数明显下降，睾丸损伤明显增加，而四组睾丸系数无明显变化。150 剂量组 Bcl-2 mRNA 水平降低，Caspase-3 升高，两个高剂量组 Bax 升高。同时，150 剂量组 Caspase-3 和 Bax 蛋白增加，三个铜处理组 Bcl-2 蛋白减少。然而，四组 3β-HSD、17β-HSD、17α-Hyd 和 20α-Hyd 的睾酮含量和睾酮合成酶水平、Cyp11a1、Cyp17a1 和 Star 的 mRNA 水平以及 Leydig 细胞数量均无差异。总之，这些数据表明，慢性铜暴露导致睾丸内铜残留，100 和 150mg/kg/天硫酸铜剂量可能通过增加凋亡而不影响睾酮分泌导致少精子症。
