RAB37-mediated autophagy guards ovarian homeostasis and function

ABSTRACT

Loss of ovarian homeostasis is associated with ovary dysfunction and female diseases; however, the underlying mechanisms responsible for the establishment of homeostasis and its function in the ovary have not been fully elucidated. Here, we showed that conditional knockout of Rab37 in oocytes impaired macroautophagy/autophagy proficiency in the ovary and interfered with follicular homeostasis and ovary development in mice. Flunarizine treatment upregulated autophagy, thus rescuing the impairment of follicular homeostasis and ovarian dysfunction in rab37 knockout mice by reprogramming of homeostasis. Notably, both the E2F1 and EGR2 transcription factors synergistically activated Rab37 transcription and promoted autophagy. Thus, RAB37-mediated autophagy ensures ovary function by maintaining ovarian homeostasis.

KEYWORDS:

• Gene knockout
• homeostasis
• mice
• ovary
• RAB37
• transcription regulation

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Acknowledgments

The authors would like to thank to professor Shuiqiao Yuan of Huazhong University of Science and Technology for providing Zp3-Cre mice and professor Yiliang Miao of Huazhong Agricultural University for mice breeding.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (32370655) and the National Key Technologies R&D Program (2019YFA0802500).