Abstract
BackgroundMammalian 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.ResultsWe 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.ConclusionsOur 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.
Highlights
IntroductionMaturation of the ovarian follicles, require both growth factors derived from oocyte and surrounding cells, including stromal cells
Mammalian folliculogenesis, maturation of the ovarian follicles, require both growth factors derived from oocyte and surrounding cells, including stromal cells
Stromal cells and stromal progenitor cell insert between closely associated germ cells followed by germ cysts breakdown as part of the progress results in primordial follicle formation
Summary
Maturation of the ovarian follicles, require both growth factors derived from oocyte and surrounding cells, including stromal cells. While SUMO2/3 proteins are localized in nucleoplasm, SUMO-1 is concentrated at spindle organization and chromosome in transcriptionally active oocytes with little location on nuclear membrane in quiescent oocytes. This specific localization of SUMO-1 plays a critical role during oocytes maturation [21,22,23]. Little is known about role of protein SUMOylation in stromal cells surrounding oocyte in regulating follicle development and oocyte maturation is unclear. We show that stromal deletion of SENP1 in mice, by increasing cellular SUMOylation and decreasing BMP4 expression, retards oocytes growth and follicle formation at early developmental stage
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