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Deficiency of Dgcr8-dependent canonical microRNAs causes infertility due to multiple spectra of abnormalities in uterine development and hormone responsiveness in mice
- 언어ENG
- URLhttps://db.koreascholar.com/Article/Detail/355403
DGCR8 is a RNA-binding protein working with DROSHA to produce pre-microRNA in the nucleus, while DICER does not only mature microRNA but also endogenous siRNAs in the cytoplasm. Here, we have produced Dgcr8 conditional knock-out mice using progesterone receptor (PR)-Cre (Dgcr8flox/flox; PRcre/+ mice, Dgcr8d/d) and demonstrated that canonical microRNAs dependent of DROSHA-DGCR8 complex are required for uterine development as well as female fertility in mice. Adult Dgcr8d/d females did not undergo regular reproductive cycle and produce any pups when housed with fertile males, whereas administration of exogenous gonadotropins induced normal ovulation with corpus luteal formation in these mice. Ovulated oocytes from Dgcr8d/d mice had comparable fertilization potentials and were normally developed to the blastocyst after fertilization as compared to those in control Dgcr8f/f mice. Interestingly, PR-Cre-dependent Dgcr8 deletion showed aberrant infiltration of acute inflammatory immune cells to female reproductive organs only when Dgcr8d/d mice were mated with male mice. With respect to uterine development, gross morphology, histology, and weight of Dgcr8d/d uterus were similar to those of control at 3-week-old age. However, multiple uterine abnormalities were noticeable at 4-week-old age when PR expression is significantly increased, and these deformities became severe onwards. Gland formation and myometrial layers were significantly reduced, and stromal cell compartment did not expand and became atrophic during uterine development in these mice. These results were consistent with aberrantly reduced cell proliferation in stromal cell compartments of Dgcr8d/d mice. Collectively, our results suggest that DGCR8 dependent-canonical microRNAs are essential for development and physiology of the uterus with respect to morphogenesis, proper immune modulation, reproductive cycle, and steroid hormone responsiveness in mice.
