Accumulated autophagosomes and excessive apoptosis during the luteal development of pregnant rats.

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.