Deficiency in DGCR8-dependent canonical microRNAs causes infertility due to multiple abnormalities during uterine development in mice

Scientific Reports
Yeon Sun KimHaengseok Song

Abstract

DGCR8 is an RNA-binding protein that interacts with DROSHA to produce pre-microRNA in the nucleus, while DICER generates not only mature microRNA, but also endogenous small interfering RNAs in the cytoplasm. Here, we produced Dgcr8 conditional knock-out mice using progesterone receptor (PR)-Cre (Dgcr8(d/d)) and demonstrated that canonical microRNAs dependent on the DROSHA-DGCR8 complex are required for uterine development as well as female fertility in mice. Adult Dgcr8(d/d) females neither underwent regular reproductive cycles nor produced pups, whereas administration of exogenous gonadotropins induced normal ovulation in these mice. Interestingly, immune cells associated with acute inflammation aberrantly infiltrated into reproductive organs of pregnant Dgcr8(d/d) mice. Regarding uterine development, multiple uterine abnormalities were noticeable at 4 weeks of age when PR is significantly increased, and the severity of these deformities increased over time. Gland formation and myometrial layers were significantly reduced, and the stromal cell compartment did not expand and became atrophic during uterine development in these mice. These results were consistent with aberrantly reduced stromal cell proliferation and completely f...Continue Reading

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Citations

Apr 30, 2017·Molecular Reproduction and Development·Sarah A RobertsonJohn E Schjenken
Nov 9, 2017·Journal of Cellular Physiology·Cristina B HebedaSandra H P Farsky
Nov 25, 2017·Reproduction : the Official Journal of the Society for the Study of Fertility·Dawit TesfayeKarl Schellander
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Nov 3, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hye-Ryun KimHaengseok Song
Jun 12, 2020·International Journal of General Medicine·Emad BabakhanzadehMahta Mazaheri
Oct 11, 2017·Frontiers in Cardiovascular Medicine·Kelsey R BoundsPiyali Chatterjee
Sep 18, 2018·International Journal of Molecular Medicine·Qianwen MaBeibei Zhou

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Methods Mentioned

BETA
genotyping
PCR
transgenic
biopsies
reverse transcription-PCR
light microscopy

Software Mentioned

Image Lab
Image J

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