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Chronic Copper Exposure Induces Hypospermatogenesis in Mice by Increasing Apoptosis Without Affecting Testosterone Secretion

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Abstract

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.

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Funding

This research was supported by the National Key R & D Program of China [grant nos. 2016YFD0501205 and 2017YFD0502200], the National Science Foundation for Young Scientists of China [grant no. 31502131], and the Youth Teacher Award Foundation of South China Agricultural University [Provided by Guangdong Wens Dahuanong Biotechnology Co., Ltd.; grant no. 5500-A17003].

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  1. College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China

    Hanming Chen, Zhenlong Kang, Na Qiao, Gaoyang Liu, Kebin Huang, Xi Wang, Congying Pang, Qiwen Zeng, Zhaoxin Tang & Ying Li

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  1. Hanming Chen
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Correspondence to Zhaoxin Tang or Ying Li.

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Chen, H., Kang, Z., Qiao, N. et al. Chronic Copper Exposure Induces Hypospermatogenesis in Mice by Increasing Apoptosis Without Affecting Testosterone Secretion. Biol Trace Elem Res 195, 472–480 (2020). https://doi.org/10.1007/s12011-019-01852-x

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