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Cell Biosci. 2017 Jul 25;7:36. doi: 10.1186/s13578-017-0163-5. eCollection 2017.

Stromal Senp1 promotes mouse early folliculogenesis by regulating BMP4 expression.

Author information

1
Department of Pathology and the Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT 06519 USA.
2
Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080 China.
3
Department of Gynecology Oncology, The Tumor Affiliated Hospital of Harbin Medical University, Harbin, China.
4
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
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Contributed equally

Abstract

BACKGROUND:

Mammalian folliculogenesis, maturation of the ovarian follicles, require both growth factors derived from oocyte and surrounding cells, including stromal cells. However, the mechanism by which stromal cells and derived factors regulate oocyte development remains unclear.

RESULTS:

We observed that SENP1, a small ubiquitin-related modifier (SUMO)-specific isopeptidase, was expressed in sm22α-positive stromal cells of mouse ovary. The sm22α-positive stromal cells tightly associated with follicle maturation. By using the sm22α-specific Cre system, we show that mice with a stromal cell-specific deletion of SENP1 exhibit attenuated stroma-follicle association, delayed oocyte growth and follicle maturation with reduced follicle number and size at early oocyte development, leading to premature ovarian failure at late stages of ovulating life. Mechanistic studies suggest that stromal SENP1 deficiency induces down-regulation of BMP4 in stromal cells concomitant with decreased expression of BMP4 receptor BMPR1b and BMPR2 on oocytes.

CONCLUSIONS:

Our data support that protein SUMOylation-regulating enzyme SENP1 plays a critical role in early ovarian follicle development by regulating gene expression of BMP4 in stroma and stroma-oocyte communication.

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