Reproductive toxicity of cadmium in pubertal male rats induced by cell apoptosis

Yi, Lingna; Dai, Juan; Chen, Yong; Tong, Yeqing; You, Li; Fu, Guoqing; Teng, Zengguang; Huang, Jufeng; Quan, Chao; Zhang, Zhibing; Zhou, Ting; Zhang, Ling; Shi, Yuqin

doi:10.1177/07482337211022615

Cited by 9 publications

(4 citation statements)

References 70 publications

(74 reference statements)

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“…Common environmental toxins include organic chemicals (such as herbicides, pesticides), metals and ionizing radiation. Numerous studies have found that Long-term exposure to environmental toxins can cause dysfunctions such as lung diseases ( 193 ), cancer ( 194 ), hepatic damage ( 195 ), especially the male reproductive disorders ( 196 ). For example, Bisphenol A (BPA) and formaldehyde are the widespread environmental pollutants, both of which can cause male reproductive injuries including testicular histopathological changes (decreased spermatogenic cells ( 144 ) or testicular tissue necrosis and edema ( 145 )), testicular oxidative stress damage(reducing testicular antioxidant enzyme activity ( 197 )) and cells apoptosis(up-regulating Bax apoptotic protein expression ( 145 )).…”

Section: The Protective Effects Of Taurine Against Male Reproductive ...mentioning

confidence: 99%

The role of taurine in male reproduction: Physiology, pathology and toxicology

Peng²,

Shang³

et al. 2023

Front. Endocrinol.

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Taurine, a sulfur-containing amino acid, has a wide range of biological effects, such as bile salt formation, osmotic regulation, oxidative stress inhibition, immunomodulation and neuromodulation. Taurine has been proved to be synthesized and abundant in male reproductive organs. Recently, accumulating data showed that taurine has a potential protective effect on reproductive function of male animals. In physiology, taurine can promote the endocrine function of the hypothalamus-pituitary-testis (HPT) axis, testicular tissue development, spermatogenesis and maturation, delay the aging of testicular structure and function, maintain the homeostasis of the testicular environment, and enhance sexual ability. In pathology, taurine supplement may be beneficial to alleviate pathological damage of male reproductive system, including oxidative damage of sperm preservation in vitro, testicular reperfusion injury and diabetes -induced reproductive complications. In addition, taurine acts as a protective agent against toxic damage to the male reproductive system by exogenous substances (e.g., therapeutic drugs, environmental pollutants, radiation). Related mechanisms include reduced oxidative stress, increased antioxidant capacity, inhibited inflammation and apoptosis, restored the secretory activity of the HPT axis, reduced chromosomal variation, enhanced sperm mitochondrial energy metabolism, cell membrane stabilization effect, etc. Therefore, this article reviewed the protective effect of taurine on male reproductive function and its detailed mechanism, in order to provide reference for further research and clinical application.

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Section: The Protective Effects Of Taurine Against Male Reproductive ...mentioning

confidence: 99%

The role of taurine in male reproduction: Physiology, pathology and toxicology

Peng²,

Shang³

et al. 2023

Front. Endocrinol.

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“…It has been reported that plasma testosterone levels and testosterone synthase activity decreased after pubertal cadmium exposure, leading to defects in development of adolescent testes and reproductive dysfunction in adult mice [ 12 ]. Animal studies demonstrated that cadmium exposure resulted in testicular toxicity including abscission of epithelial cells, apoptosis of testicular germ cells and lower level of testosterone, eventually leading to spermatogenesis defects and declined sperm quality [ 13 , 14 ]. Nonetheless, the implications of cadmium-related damage to Leydig cells have received scant attention [ 15 , 16 ], and the underlying mechanism of cytotoxicity and apoptosis remains to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Cadmium-induced apoptosis of Leydig cells is mediated by excessive mitochondrial fission and inhibition of mitophagy

Shang

et al. 2022

Cell Death Dis

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Cadmium is one of the environmental and occupational pollutants and its potential adverse effects on human health have given rise to substantial concern. Cadmium causes damage to the male reproductive system via induction of germ-cell apoptosis; however, the underlying mechanism of cadmium-induced reproductive toxicity in Leydig cells remains unclear. In this study, twenty mice were divided randomly into four groups and exposed to CdCl2 at concentrations of 0, 0.5, 1.0 and 2.0 mg/kg/day for four consecutive weeks. Testicular injury, abnormal spermatogenesis and apoptosis of Leydig cells were observed in mice. In order to investigate the mechanism of cadmium-induced apoptosis of Leydig cells, a model of mouse Leydig cell line (i.e. TM3 cells) was subjected to treatment with various concentrations of CdCl2. It was found that mitochondrial function was disrupted by cadmium, which also caused a significant elevation in levels of mitochondrial superoxide and cellular ROS. Furthermore, while cadmium increased the expression of mitochondrial fission proteins (DRP1 and FIS1), it reduced the expression of mitochondrial fusion proteins (OPA1 and MFN1). This led to excessive mitochondrial fission, the release of cytochrome c and apoptosis. Conversely, cadmium-induced accumulation of mitochondrial superoxide was decreased by the inhibition of mitochondrial fission through the use of Mdivi-1 (an inhibitor of DRP1). Mdivi-1 also partially prevented the release of cytochrome c from mitochondria to cytosol and attenuated cell apoptosis. Finally, given the accumulation of LC3II and SQSTM1/p62 and the obstruction of Parkin recruitment into damaged mitochondria in TM3 cells, the autophagosome-lysosome fusion was probably inhibited by cadmium. Overall, these findings suggest that cadmium induces apoptosis of mouse Leydig cells via the induction of excessive mitochondrial fission and inhibition of mitophagy.

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“…Recently, Cd-induced male reproductive toxicity has drawn the attention from many researchers [11,12].…”

Section: Introductionmentioning

confidence: 99%

Cadmium exposure causes mouse spermatogonia apoptosis via inducing endoplasmic reticulum stress

Wu,

Yin,

Wang

et al. 2024

Preprint

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Cadmium (Cd), which can cause testicular germ cell apoptosis, is a well-recognized male reproductive toxicant, but the underlying mechanism still needs investigation. To detect Cd toxicity on testicular germ cell, we treated mouse spermatogonia with CdCl2 in vitro and investigated the responses from cells at both RNA and protein levels. After treating mouse-derived spermatogonia cell line GC-1 spg cells with 20 µM CdCl2 for 24h, cell apoptosis was measured by TUNEL and flow cytometry assay. After then, the expressions of key genes and protein biomarkers involved in endoplasmic reticulum (ER) stress were detected by qPCR and western blot, respectively. Finally, untargeted metabolomics was performed to compare metabolic differences, and Illumina RNA sequencing was conducted to screen differentially expressed genes (DEGs). Our results indicated that Cd exposure caused cell apoptosis, DEGs were involved in several apoptosis-related pathways. Cd exposure apparently elevated the mRNA and protein expressions levels of both GRP78 and ATF6α, and disrupted the expression of many types of metabolites, especially for amino acids. Taken together, our study uncovers the pathway of Cd toxicity on mouse spermatogonia, provides deep understanding on Cd-induced testicular toxicity.

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Reproductive toxicity of cadmium in pubertal male rats induced by cell apoptosis

Cited by 9 publications

References 70 publications

The role of taurine in male reproduction: Physiology, pathology and toxicology

The role of taurine in male reproduction: Physiology, pathology and toxicology

Cadmium-induced apoptosis of Leydig cells is mediated by excessive mitochondrial fission and inhibition of mitophagy

Cadmium exposure causes mouse spermatogonia apoptosis via inducing endoplasmic reticulum stress

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