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The contribution of autophagy to catabolic balance has been well-established in various types of cells, whereas the involvement of autophagy in progesterone synthesis during rat pregnancy still remains unknown. Therefore, the present study was designed to evaluate the role of autophagy in progesterone production during the luteal development of pregnant rats. The results showed autophagy-related proteins was maintained at a low level on day 10 after pregnancy, significantly induced on day 16 and subsided to a relative low level on day 21, which was consistent with the changes of serum progesterone levels. The findings further indicated the contribution of autophagy to progesterone production was regulated by inactivation of Akt/mTOR signaling during the luteal development of pregnant rats in in vivo and in vitro experiments. Further investigations revealed autophagy may be involved in the surge of progesterone production in pregnant rats, as inhibition of autophagy by 3-MA compromised serum progesterone levels. Furthermore, 3-MA treatment also leveled down the number of lipid droplets in luteal cells, implying that autophagy may affect the production of progesterone by manipulating the formation of lipid droplets in luteal cells. In addition, the results suggested that mitophagy was mobilized during the primary stage of luteolysis and inhibition of autophagy promoted the increase of redundant mitochondrial and cytoplasmic cytochrome C in luteal cells of pregnant rats. Taken together, the present study indicated that autophagy-related proteins were induced by the inactivation of Akt/mTOR signaling and then contributed to the progesterone production possibly by affecting the formation of intracellular lipid droplets during the luteal development of pregnant rats. To our knowledge, this will provide a new insight into the important mechanism of autophagy regulating progesterone production in ovaries of pregnant mammals.

Autophagy Attenuation Hampers Progesterone Synthesis during the Development of Pregnant Corpus Luteum