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Publication : Bone morphogenetic protein 2- and estradiol-17β-induced changes in ovarian transcriptome during primordial follicle formation†.

First Author  Chakraborty P Year  2022
Journal  Biol Reprod Volume  107
Issue  3 Pages  800-812
PubMed ID  35639639 Mgi Jnum  J:334514
Mgi Id  MGI:7448655 Doi  10.1093/biolre/ioac111
Citation  Chakraborty P, et al. (2022) Bone morphogenetic protein 2- and estradiol-17beta-induced changes in ovarian transcriptome during primordial follicle formation. Biol Reprod 107(3):800-812
abstractText  Estradiol-17beta has been shown to promote primordial follicle formation and to involve bone morphogenetic protein 2 (BMP2) as a downstream effector to promote primordial follicle in hamsters. However, the molecular mechanism whereby these factors regulate ovarian somatic cells to pre-granulosa cells transition leading to primordial follicle formation remains unclear. The objective of this study was to determine whether BMP2 and/or estradiol-17beta would regulate the expression of specific ovarian transcriptome during pre-granulosa cells transition and primordial follicle formation in the mouse ovary. BMP2 mRNA level increased during the period of primordial follicle formation with the concurrent presence of BMP2 protein in ovarian somatic cells. Estradiol-17beta but not BMP2 exposure led to increased expression of ovarian BMP2 messenger RNA (mRNA), and the effect of estradiol-17beta could not be suppressed by 4-[6-[4-(1-Piperazinyl)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline dihydrochloride (LDN) 193189. BMP2 or estradiol-17beta stimulated primordial follicle formation without inducing apoptosis. Ribonucleic acid-sequence analysis (RNA-seq) of ovaries exposed to exogenous BMP2 or estradiol-17beta revealed differential expression of several thousand genes. Most of the differentially expressed genes, which were common between BMP2 or estradiol-17beta treatment demonstrated concordant changes, suggesting that estradiol-17beta and BMP2 affected the same set of genes during primordial follicle formation. Further, we have identified that estradiol-17beta, in cooperation with BMP2, could affect the expression of three major transcription factors, GATA binding protein 2, GATA binding protein 4 and Early growth response 2, and one serine protease, hepsin, in pre-granulosa cells during primordial follicle formation. Taken together, results of this study suggest that estradiol-17beta and BMP2 may regulate ovarian gene expression that promote somatic cells to pre-granulosa cells transition and primordial follicle formation in the mouse ovary.
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