Hypomethylation of LINE-1 retrotransposons is associated with cadmium-induced testicular injury
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RESEARCH ARTICLE
Hypomethylation of LINE-1 retrotransposons is associated with cadmium-induced testicular injury Xiaofei Wang 1
&
Mei Wang 2 & Ling Zeng 1 & Ping Su 1
Received: 14 January 2020 / Accepted: 13 July 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Retrotransposons, as vital regulator of male fertility, are essential for spermatogenesis. Cadmium (Cd) is an environmental toxicant and endocrine disruptor, targeting the reproductive system. Growing evidence shows that Cd exposure can induce male infertility in mammals. In this study, we generated a male C57BL/6 J mice model with consecutive 35 days cadmium chloride (CdCl2) in different concentrations of 0, 0.25, 0.5, 1.0, and 2.0 mg/kg. The results indicated that 1.0 and 2.0 mg/kg CdCl2 significantly affected the body weight. Meanwhile, the highest dose group with 2.0 mg/kg CdCl2 presented low fertility. Furthermore, the expression of retrotransposon mRNA was markedly increased in the higher doses group. We examined methylcytosine (mC) levels of the three active LINE-1 subfamilies TfI, A, and GfII in testis. Conclusively, Cd exposure probably undermines the male mice fertility by disrupting DNA methylation to regulate the retrotransposons. Further studies are required for identifying whether retrotransposon activation has any significant impacts on genome structure, stability, and expression in Cd-induced testicular injury, laying foundation for the treatment for male infertility. Keywords Retrotransposons . LINE-1 . Cadmium . Testis . DNA methylation
Introduction With the advancement of industrialization, heavy metal pollution has become a major environmental issue in modern times. Cd is a nonessential cumulative toxic metal that harms human health through contaminated foods, water, and air (Hossain et al. 2012). Once absorbed, Cd efficiently accumulates in the human body, mainly in the kidneys, where it is retained with a biological halftime around 10–30 years (Jarup and Akesson 2009). The low-level lifetime exposure to this metal may lead to damage to the kidneys, liver, skeletal system, and cardiovascular system, as well as to the deterioration of the sight and hearing (Mezynska and Brzoska 2018; Nan et al. Responsible Editor: Mohamed M. Abdel-Daim * Ping Su [email protected] 1
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People’s Republic of China
2
Department of Obstetrics and Gynecology/Reproduction Medicine Center, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei, People’s Republic of China
2020). Moreover, environmental exposure to this xenobiotic may contribute to the development of cancer of the lung, breast, prostate, pancreas, urinary bladder, and nasopharynx (Daud et al. 2009; Li et al. 2020). Increasing research indicates that environmental exposure to Cd is related to poor semen quality and male infertility (Saygi et al. 1991). The testicles are particularly susceptible to Cd, and testicular damage can be
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