Bisphenol A Exposure Induces Apoptosis and Upregulation of Fas/FasL and Caspase-3 Expression in the Testes of Mice

Li, Yuan-Jie; Song, Tianbao; Cai, Yanyan; Zhou, Jinsong; Xiao, Song; Zhao, Xuan; Wu, Xiaolin

doi:10.1093/toxsci/kfp024

Cited by 177 publications

(123 citation statements)

References 39 publications

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“…The apoptosis of the cells, identified as caspase-3-immunopositive cells was found in testes of pubertal mice exposed to different dose of bisphenol A (BPA). The effect resulted from decreased expression of steroidogenic enzymes in Leydig cells induced by the xenoestrogen [69]. Peritubular myoid cells maintain the morphology of the seminiferous tubules participating in the formation of the basement membrane.…”

Section: Discussionmentioning

confidence: 99%

The immunoexpression of androgen receptor, estrogen receptors alpha and beta, vanilloid type 1 receptor and cytochrome p450 aromatase in rats testis chronically treated with letrozole, an aromatase inhibitor

Pilutin

Misiakiewicz-Has²,

Kolasa³

et al. 2014

Folia Histochem Cytobiol.

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Abstract:The function of testis is under hormonal control and any disturbance of hormonal homeostasis can lead to morphological and physiological changes. Therefore the aim of the study was to investigate the expression of androgen and estrogen receptors (AR, ERs), vanilloid receptor (TRPV1), cytochrome P450 aromatase (P450arom), as well as apoptosis of cells in testis of adult rats chronically treated with letrozole (LT), a non-steroidal aromatase inhibitor, for 6 months. The testicular tissues were fixed in Bouin's fixative and embedded in paraffin. Immunohistochemistry with monoclonal antibodies (abs) against AR, ERa, P450arom, and polyclonal abs against ERb, TRPV1, caspase-3 was applied. Long-lasting estradiol deficiency, as an effect of LT treatment, produced changes in the morphology of testis and altered the expression of the studied receptors in cells of the seminiferous tubules and rate of cell apoptosis. The immunostaining for AR was found in the nuclei of Sertoli cells and the cytoplasm of spermatogonia and spermatocytes in III-IV stages of the seminiferous epithelium cycle. The intensity of staining for P450arom was lower in the testis of LT-treated rats as compared to control animals. The immunofluorescence of ERa and ERb was observed exclusively in the nuclei of Leydig cells of LT-treated rats. There were no changes in localization of TRPV1, however, the intensity of reaction was stronger in germ cells of the seminiferous epithelium after LT treatment. The apoptosis in both groups of animals was observed within the population of spermatocytes and spermatids in II and III stages of the seminiferous epithelium cycle. In testis of LT-treated rats the immunoexpression of caspase-3 was additionally found in the germ cells in I and IV stages, and Sertoli, myoid and Leydig cells. In conclusion, our results underline the important role of letrozole treatment in the proper function of male reproductive system, and additionally demonstrate that hormonal imbalance can produce the morphological abnormalities in testis.

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Section: Discussionmentioning

confidence: 99%

The immunoexpression of androgen receptor, estrogen receptors alpha and beta, vanilloid type 1 receptor and cytochrome p450 aromatase in rats testis chronically treated with letrozole, an aromatase inhibitor

Pilutin

Misiakiewicz-Has²,

Kolasa³

et al. 2014

Folia Histochem Cytobiol.

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“…BPA can also induce free radical generation with oxidative stress, thereby reducing epididymal or testicular sperm counts, and increasing DNA damage and cell apoptosis. This has been considered an important factor in testicular structural damage and dysfunction [Anjum et al 2011;Korkmaz et al 2010;Li et al 2009;Meeker et al 2010].…”

Section: Introductionmentioning

confidence: 99%

Protective effect of Cordyceps militaris extract against bisphenol A induced reproductive damage

Wang

Chen

Jiang

et al. 2016

Systems Biology in Reproductive Medicine

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“…Selective deletion of damaged germ cells is clearly a critical component of the mechanisms used to safeguard the genome of a given species. The range of stimuli that will trigger this activity is impressively broad including various forms of electromagnetic radiation, environmental toxicants, heavy metals and chemotherapeutic agents (Xu et al, 1999;Wang et al, 2007;Li et al, 2009;Alam et al, 2010;Shaha et al, 2010). In addition, genetic perturbance of the germ line through, for example, overexpression of SPATA 17 266 R.J. Aitken and M.A.…”

mentioning

confidence: 99%

Causes and consequences of apoptosis in spermatozoa; contributions to infertility and impacts on development

Aitken¹,

Baker²

2013

Int. J. Dev. Biol.

169

108

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During early development, apoptosis plays a major role in the ontogeny of the germ line as a means of regulating the germ cell:Sertoli cell ratio. In the adult, apoptosis fulfils another function in removing damaged germ cells from the seminiferous epithelium in response to a wide range of physiological and environmental triggers. These include various forms of electromagnetic radiation, chemotherapeutic agents and commonly encountered toxicants such as phthalate esters, bisphenol A and cadmium. This form of apoptosis can lead to spermatogenic arrest and is predominantly mediated by the Fas/FasL system. In addition, senescent mature spermatozoa can undergo a truncated form of apoptosis in order to ensure their efficient phagocytosis within the male and female reproductive tracts. This apoptotic cascade appears to be triggered by oxidative stress and lipid peroxidation, which leads to activation of mitochondrial reactive oxygen species (ROS) generation in a self-perpetuating redox cycle. The electrophilic aldehydes generated as a result of lipid peroxidation also lead to a rapid loss of sperm motility followed some hours later by caspase activation and phosphatidylserine exposure on the sperm surface. The nuclear DNA suffers oxidative damage during this process but there is no immediate DNA cleavage by endonucleases as there is in somatic cells. The reasons for this deviation from the normal pattern of apoptosis involve the unusual physical architecture of spermatozoa and the limited capacity these cells possess for base-excision repair. These findings have practical implications for the approaches that might be used to detect and prevent DNA damage in spermatozoa. KEY WORDS: spermatozoa, apoptosis, reactive oxygen species, mitochondria DNA damage Apoptosis and male germ cell developmentApoptosis is a major feature of male germ cell development that orchestrates the production and function of these cells from the early stages of gonadal differentiation to the moment of fertilization. Towards the end of embryogenesis a major wave of germ cell apoptosis occurs in prospermatogonia/gonocytes when the testes are differentiating and adjustments have to be introduced to achieve the optimal germ cell:Sertoli cell ratio. During this developmental process, excess premeiotic spermatogonia are removed by apoptosis during the first round of spermatogenesis in the testis. Impairment of apoptosis through the functional deletion of key mediators of this process generates a male infertility phenotype due to an imbalance in germ-and Sertoli-cell numbers (Rodriguez et al., 1997). This regulatory role for apoptosis in the male germ cell development is very similar to the situation in the differentiating female gonad where there is also a wave of apoptosis in the ovary Int. J. Dev. Biol. 57: 265-272 (2013) as germ cells are eliminated that have not found somatic cells with which to form primordial follicles .In adulthood, apoptosis again plays a significant role in regulating germ cell development. For example, apoptosis ...

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Bisphenol A Exposure Induces Apoptosis and Upregulation of Fas/FasL and Caspase-3 Expression in the Testes of Mice

Cited by 177 publications

References 39 publications

The immunoexpression of androgen receptor, estrogen receptors alpha and beta, vanilloid type 1 receptor and cytochrome p450 aromatase in rats testis chronically treated with letrozole, an aromatase inhibitor

The immunoexpression of androgen receptor, estrogen receptors alpha and beta, vanilloid type 1 receptor and cytochrome p450 aromatase in rats testis chronically treated with letrozole, an aromatase inhibitor

Protective effect of Cordyceps militaris extract against bisphenol A induced reproductive damage

Causes and consequences of apoptosis in spermatozoa; contributions to infertility and impacts on development

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