Autophagy Contributes to Oxidative Stress-Induced Apoptosis in Porcine Granulosa Cells
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REPRODUCTIVE BIOLOGY: ORIGINAL ARTICLE
Autophagy Contributes to Oxidative Stress-Induced Apoptosis in Porcine Granulosa Cells Jia-Qing Zhang 1,2 & Qiao-Ling Ren 1,2 & Jun-Feng Chen 1,2 & Bin-Wen Gao 1,2 & Xian-Wei Wang 3 & Zi-Jing Zhang 1,2 & Jing Wang 1,2 & Ze-Jun Xu 3 & Bao-Song Xing 1,2 Received: 5 June 2020 / Accepted: 1 October 2020 # Society for Reproductive Investigation 2020
Abstract Oxidative stress-induced granulosa cell (GC) death is a major cause of follicular atresia. As the major types of programmed cell death, autophagy and apoptosis have been observed in response to H2O2-mediated oxidative stress and have been demonstrated to be responsible for porcine GC death. To date, however, the cellular reactions linking autophagy to the apoptosis of porcine GC under oxidative stress are still poorly understood. Porcine GC were treated with H2O2, and autophagic flux was examined by western blotting. Cell viability and cell death assays were performed after cotreatment of porcine GC with autophagy activator (rapamycin) or inhibitor (3-methyladenine, 3-MA) together with H2O2. We revealed that short exposure (1–3 h) of porcine GC to H2O2 dramatically increased autophagic flux (1.8- to 2.5-fold over that in the control), whereas 6–12 h prolonged treatment decreased autophagy but elevated the caspase-3 activity and GC apoptotic rate. Furthermore, we showed that pretreatment with rapamycin exacerbated H2O2-mediated cytotoxicity and caspase-3 activation but that 3-MA or siRNAs specific for Beclin 1 and Atg7 genes ameliorated H2O2-mediated GC apoptosis. Together, our results indicate that autophagy plays a pivotal role in H2O2mediated porcine GC apoptosis. Importantly, we show that the early induction of autophagic flux contributes to oxidative stressinduced apoptosis in porcine GC. The results also suggest that regulating the autophagy response in porcine GC under oxidative stress might be a new strategy for abnormal follicular atresia. Keywords Autophagy . Apoptosis . Porcine granulosa cells . Oxidative stress
Introduction Approximately 5 million primordial follicles are present in both ovaries 10 days after birth in sows, whereas the overwhelming majority of follicles undergo atresia during growth Electronic supplementary material The online version of this article (https://doi.org/10.1007/s43032-020-00340-1) contains supplementary material, which is available to authorized users. * Jia-Qing Zhang [email protected] Bao-Song Xing [email protected] 1
Institute of Animal Husbandry and Veterinary Science, Henan Academy of Agricultural Sciences, Zhengzhou 450002, China
2
Henan Key Laboratory of Farm Animal Breeding and Nutritional Regulation, Zhengzhou 450002, China
3
Henan Provincial Animal Husbandry General Station, Zhengzhou 450008, China
and development [25]. Abnormal follicular atresia may accelerate the depletion of the ovarian follicular reserve, resulting in reproductive dysfunction [6]. Many studies have indicated that granulosa cell (GC) apoptosis plays a key role in follicular atresia [11, 48,
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