Tang Zonghao, Huang Yuxiu, Zhang Zhenghong, Tang Yedong, Chen Jiajie, Sun Fengqi, Yang Hongqin, Wang Zhengchao
Provincial Key Laboratory for Developmental Biology and Neurosciences, College of Life Sciences, Fujian Normal University Fuzhou, China.
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Fujian Medical University Fuzhou, China.
Int J Clin Exp Pathol. 2017 Dec 1;10(12):11384-11392. eCollection 2017.
Autophagy plays an important role in the regression of pseudopregnant corpus luteum, whereas the involvement of autophagy in the pregnant luteolysis still remains unknown. Therefore, the present study was designed to investigate the levels and effects of accumulated autophagosomes on excessive apoptosis during the luteal development of pregnant rats. Ovaries were obtained from the female rats at the early, middle or late phase of the pregnancy, which correspondingly had three groups; including the early (ELP), middle (MLP) and late luteal phase (LLP). The results of autophagy-associated protein LC-3 clearly showed that autophagy expressed during the pregnant CL and significantly increased at LLP, while the expression changes of apoptosis related proteins cleaved caspase-3 and Bax were similar with LC-3 expression changes, indicating autophagy may be involved in the initiation of pregnant luteolysis through the induction of cellular apoptosis at LLP of pregnant ovaries. The present study was further examined the expressions of other two autophagy-associated proteins p62 and LAMP-2, since the degradation failure of autophagosomes contributed to cellular apoptosis. The results demonstrated p62 protein was accumulated at LLP while its mRNA was maintained during the whole luteal development of pregnant rats. Interestingly, the expressions of LAMP-2 mRNA and premature protein were significantly increased at MLP and LLP, while the expression of mature LAMP-2 increased at MLP and then decreased at LLP, implying autophagosomes were accumulated at LLP. Together, to our knowledge, the present study firstly demonstrated that the insufficient of lysosomal functions contributed to the impaired degradation of autophagosomes and then activated caspase-3 dependent apoptotic pathway during the pregnant luteolysis of rat ovaries, which will provide a new insight into the important mechanism regulating the luteolysis of the pregnant ovaries in mammals.
自噬在假孕黄体的消退过程中发挥重要作用，而自噬在妊娠黄体溶解中的作用仍不清楚。因此，本研究旨在探讨妊娠大鼠黄体发育过程中积累的自噬体对过度凋亡的水平及影响。从处于妊娠早期、中期或晚期的雌性大鼠获取卵巢，相应地分为三组，即早期黄体期（ELP）、中期黄体期（MLP）和晚期黄体期（LLP）。自噬相关蛋白LC-3的结果清楚显示，自噬在妊娠黄体中表达，并在LLP时显著增加，而凋亡相关蛋白裂解的caspase-3和Bax的表达变化与LC-3表达变化相似，表明自噬可能通过诱导妊娠卵巢LLP时的细胞凋亡参与妊娠黄体溶解的起始。由于自噬体降解失败会导致细胞凋亡，本研究进一步检测了另外两种自噬相关蛋白p62和LAMP-2的表达。结果表明，p62蛋白在LLP时积累，而其mRNA在妊娠大鼠整个黄体发育过程中保持稳定。有趣的是，LAMP-2 mRNA和前体蛋白的表达在MLP和LLP时显著增加，而成熟LAMP-2的表达在MLP时增加，然后在LLP时下降，这意味着自噬体在LLP时积累。总之，据我们所知，本研究首次证明溶酶体功能不足导致自噬体降解受损，进而在大鼠卵巢妊娠黄体溶解过程中激活caspase-3依赖性凋亡途径，这将为调控哺乳动物妊娠卵巢黄体溶解的重要机制提供新的见解。
