Hypoxia induces apoptosis of mouse spermatocyte GC‐2 cells through activation of autophagy

Zhou, Jian; Qian, Chun-Ya; Tong, Ruiqing; Wang, Bin; Chen, Xuelei; Zhuang, Yanyan; Xia, Fei; He, Qian; Lv, Jinxing

doi:10.1002/cbin.10971

Cited by 14 publications

(6 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…GC-2spd cells are immortalized cells derived from mouse spermatocytes that have been applied in research on the reproductive effects of toxicants, such as cigarette smoke ( Esakky et al, 2014 ), cadmium ( Seong et al, 2019 ), and di (2-ethylhexyl) phthalate (DEHP; ( Fu et al, 2017 )), and environmental factors, such as hypoxia ( Zhou et al, 2018 ), fine particulate matter (PM 2.5 ; ( Zhang Y. et al, 2018 )), and silica nanoparticles (SiNPs; ( Ren et al, 2019 )). Both the GC-2spd cell line and the spermatocytes isolated from mouse testes could be used to study early spermatogenesis.…”

Section: Discussionmentioning

confidence: 99%

Alterations of RNA Modification in Mouse Germ Cell-2 Spermatids Under Hypoxic Stress

Guo

Xia

et al. 2022

Front. Mol. Biosci.

View full text Add to dashboard Cite

Hypoxia is a known stress factor in mammals and has been shown to potentially impair male fertility, which manifests as spermatogenic dysfunction and decreased semen quality. Studies have shown that RNA modifications, the novel post-transcriptional regulators, are involved in spermatogenesis, and hypoxia-induced alterations in RNA modification in testes and sperm cells may be associated with impaired spermatogenesis in mice. However, the molecular mechanisms via which RNA modifications influence spermatogenesis under hypoxic stress conditions are unclear. In this study, we generated a mouse Germ Cell-2 spermatid (GC-2spd) hypoxia model by culturing cells in a 1% O2 incubator for 48 h or treating them with CoCl2 for 24 h. The hypoxia treatment significantly inhibited proliferation and induced apoptosis in GC-2spd cells. The RNA modification signatures of total RNAs (2 types) and differentially sized RNA fragments (7 types of approximately 80 nt-sized tRNAs; 9 types of 17–50 nt-sized sncRNAs) were altered, and tRNA stability was partially affected. Moreover, the expression profiles of sncRNAs, such as microRNAs, tsRNAs, rsRNAs, and ysRNAs, were significantly regulated, and this might be related to the alterations in RNA modification and subsequent transcriptomic changes. We comprehensively analyzed alterations in RNA modification signatures in total RNAs, tRNAs (approximately 80 nt), and small RNAs (17–50 nt) as well as the expression profiles of sncRNAs and transcriptomes in hypoxia-treated GC-2spd cells; our data suggested that RNA modifications may be involved in cellular responses under hypoxic stress conditions and could provide a basis for a better understanding of the molecular mechanisms underlying male infertility.

show abstract

Section: Discussionmentioning

confidence: 99%

Alterations of RNA Modification in Mouse Germ Cell-2 Spermatids Under Hypoxic Stress

Guo

Xia

et al. 2022

Front. Mol. Biosci.

View full text Add to dashboard Cite

show abstract

“…Inhibiting the expression of autophagy-related proteins reduced ischemia/reperfusion induced proximal and distal tubular apoptosis and autophagy and renal failure (Chien et al, 2007). Hypoxia could also induce apoptosis of mouse spermatocyte GC-2 cells by activating autophagy (Zhou et al, 2018). The hyperactivation of autophagy is considered an important pathogenic mechanism for hypoxic-ischemic lung injury (Ye et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Hypoxia induced apoptosis of rat gastric mucosal cells by activating autophagy through HIF-1α/TERT/mTORC1 pathway

WANG¹,

Xue²,

Zhao³

et al. 2022

Biocell

View full text Add to dashboard Cite

The pathogenesis of high altitude-related gastric mucosal injury remains poorly understood, this study aimed to investigate the role of autophagy in hypoxia-induced apoptosis of rat gastric mucosal cells. Rats were randomized into four groups which were maintained at an altitude of 400 m (P) or received no treatment (H), autophagy inducer rapamycin (H+AI) or autophagy inhibitor 3-MA (H+AB) at an altitude of 4,300 m for 1, 7, 14 and 21 days, respectively, and the morphology, ultrastructure, autophagy, and apoptosis of gastric mucosal tissues were examined. Gastric mucosal epithelial cells CC-R039 were cultured under conditions of normoxia, 2% O 2 (hypoxia), or 2% O 2 +anti-mTORC1 for 0, 24, 48, and 72 h, respectively, and the autophagy and apoptosis were analyzed. CC-R039 cells were transfected with siHIF-1α, siTERT, or siRNA and the autophagy was examined. The results showed that the exposure to hypoxia increased the autophagy and apoptosis of gastric mucosal cells in rats, and apoptosis was aggravated by rapamycin treatment but alleviated by 3-MA treatment. Increased duration of hypoxia from 0 to 72 h could increase the autophagy and apoptosis but decrease the proliferation of gastric mucosal cells. Inhibition of mTORC1 with rapamycin led to further increase in apoptosis and even substantial cell death, and inhibition of HIF-1α and TERT increased mTORC1 expression and reduced autophagy. Moreover, the inhibition of HIF-1α reduced TERT expression. In conclusion, hypoxia could induce apoptosis of rat gastric mucosal cells by activating autophagy through HIF-1α/TERT/mTORC1 pathway. Abbreviations 3-MA:3-methyladenine HIF-1α:Hypoxia-inducible factor 1α LC3-II:Microtubule-associated protein light chain 3-II mTORC1: Mammalian target of rapamycin complex 1 TERT:Telomerase reverse transcriptase

show abstract

“…Ideal in vitro models for spermatocyte meiosis research are still lacking ( Ibtisham et al, 2017 ; Lei et al, 2020 ). GC-2spd cells, as the cell line closest to spermatocytes, are often used to perform basic spermatocyte research ( Zhou et al, 2018 ; Liang et al, 2020 ). Disappointingly, the morphology of GC-2spd cells is quite different from that of spermatocytes, and these cells do not express some of the marker proteins of spermatocytes, complicating acquisition of convincing results on spermatocyte meiosis from GC-2spd cells ( Hofmann et al, 1994 ; Wolkowicz et al, 1996 ).…”

Section: Discussionmentioning

confidence: 99%

A Novel Meiosis-Related lncRNA, Rbakdn, Contributes to Spermatogenesis by Stabilizing Ptbp2

et al. 2021

View full text Add to dashboard Cite

Spermatocyte meiosis is the cornerstone of mammalian production. Thousands of long noncoding RNAs (lncRNAs) have been reported to be functional in various cellular processes, but the function of lncRNAs in meiosis remains largely unknown. Here, we profiled lncRNAs in spermatocytes at stage I of meiosis and identified a testis-specific lncRNA, Rbakdn, as a vital regulator of meiosis. Rbakdn is dynamically expressed during meiosis I, and Rbakdn knockdown inhibits meiosis in vitro. Furthermore, Rbakdn knockdown in testes in mice by intratesticular injection disturbs meiosis, reduces testicular volume, and increases apoptosis of spermatocytes, resulting in vacuolation of the seminiferous tubules. Rbakdn can bind to Ptbp2, an RNA-binding protein that is important in the regulation of the alternative splicing of many genes in spermatogenesis. Rbakdn knockdown leads to a decrease in Ptbp2 through the ubiquitination degradation pathway, indicating that Rbakdn maintains the stability of Ptbp2. In conclusion, our study identified an lncRNA, Rbakdn, with a crucial role in meiosis.

show abstract

Hypoxia induces apoptosis of mouse spermatocyte GC‐2 cells through activation of autophagy

Cited by 14 publications

References 39 publications

Alterations of RNA Modification in Mouse Germ Cell-2 Spermatids Under Hypoxic Stress

Alterations of RNA Modification in Mouse Germ Cell-2 Spermatids Under Hypoxic Stress

Hypoxia induced apoptosis of rat gastric mucosal cells by activating autophagy through HIF-1α/TERT/mTORC1 pathway

A Novel Meiosis-Related lncRNA, Rbakdn, Contributes to Spermatogenesis by Stabilizing Ptbp2

Contact Info

Product

Resources

About