Observation of Parthanatos Involvement in Diminished Ovarian Reserve Patients and Melatonin's Protective Function Through Inhibiting ADP-Ribose (PAR) Expression and Preventing AIF Translocation into the Nucleus
Observation of Parthanatos Involvement in Diminished Ovarian Reserve Patients and Melatonin's Protective Function Through Inhibiting ADP-Ribose (PAR) Expression and Preventing AIF Translocation into the Nucleus
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DOI：
10.1007/s43032-019-00005-8
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发表时间：
2020-01-01
影响因子：
2.9
通讯作者：
Li, Yanping
中科院分区：
文献类型：
--
作者：
Batnasan, Enkhzaya;Kie, Shi;Li, Yanping
卵巢储备减少(DOR)的特征是卵巢池的耗尽，导致卵母细胞质量和数量的减少。研究表明，卵巢储备或卵巢老化与细胞凋亡密切相关。然而，对细胞死亡机制的认识还不够全面。甲状旁腺激素是一种依赖多聚[ADP-核糖]聚合酶1(PARP1)的凋亡诱导因子(AIF)介导的细胞死亡，在多种疾病中起重要作用。在目前的研究中，我们的目的是调查副死神是否参与了DOR的发病机制。我们招募了40名患者(20名DOR患者和20名正常卵巢储备(NOR)患者)，并在荧光显微镜下检测了他们分离的卵丘GC(颗粒细胞)中PAR的表达和AIF移位。我们的结果表明，DOR患者卵丘GCs中PAR的表达和AIF核转位显著增加，提示PARP1依赖性细胞死亡可能与DOR的病理生理有关。此外，我们还检测了褪黑素对过氧化氢(H_2O_2)诱导的人卵巢癌细胞(IGROV_1)甲胎蛋白的保护作用。我们的结果表明，过氧化氢处理IGROV1细胞会导致过度的蛋白质PAR化和AIF移位到细胞核内。褪黑素有效地抑制PAR化，阻止AIF移位到细胞核内，从而降低卵丘GC发生副死胎的风险。
Diminished ovarian reserve (DOR) is characterized by the depletion of the ovarian pool, which leads to reductions in oocyte quality and quantity. Studies have suggested that ovarian reserve or ovarian aging is tightly related to apoptosis. However, the cell death mechanism is not comprehensively understood. Parthanatos, a type of poly [ADP-ribose] polymerase 1(PARP1)-dependent and apoptosis-inducing factor (AIF)-mediated cell death, plays a crucial role in various disorders. In the present study, we aimed to investigate whether parthanatos is involved in the pathogenesis of DOR. We recruited 40 patients (20 DOR patients and 20 normal ovarian reserve (NOR) patients) and examined PAR expression and AIF translocation in their isolated cumulus GCs (granulosa cells) by fluorescence microscopy. Our results demonstrated that PAR expression and AIF nuclear translocation were significantly higher in cumulus GCs of DOR patients, suggesting that PARP1-dependent cell death may be associated with DOR pathophysiology. Moreover, we tested the protective function of melatonin on hydrogen peroxide (H2O2)-induced parthanatos in human ovarian cancer (IGROV1) cells. Our results demonstrated that H2O2 treatment of IGROV1 cells led to excessive protein PARylation and AIF translocation into the nuclei. Melatonin effectively inhibits PARylation, blocks translocation of AIF into the nucleus, and consequently decreases the risk of parthanatos in cumulus GCs.