title: MiR-125b Regulates Primordial Follicle Assembly by Targeting Activin Receptor Type 2a in Neonatal Mouse Ovary.
abstract: The establishment of the primordial follicle pool is crucial for fertility in mammalian females, and the interruption of overall micro-RNA production byDicer1conditional knockout in the female reproductive system results in infertility. However, there are few reports about the functions of individual micro-RNA in regulating primordial follicle assembly. The present study aimed to investigate the function of miR-125b, which is conserved and preferentially expressed in mammalian ovary during primordial follicle assembly. Detection of miR-125b in the developing mouse ovaries by real-time PCR and in situ hybridization showed that it was highly expressed perinatally and specifically located in the ovarian somatic cells. MiR-125b overexpression blocked the process of primordial follicle assembly in cultured newborn mouse ovaries, while its knockdown promoted this process. Further studies showed that miR-125b regulated the activin/Smad2 signaling in neonatal mouse ovary by directly targeting the 3'-untranslated region of activin receptor type 2a (Acvr2a). Overexpression of miR-125b in neonatal mouse ovary suppressed theAcvr2aprotein level, attenuating activin/Smad2 signaling, while knockdown of miR-125b showed the opposite effects. In addition, recombinant human activin A (rh-ActA) down-regulated miR-125b in the neonatal mouse ovary. Overexpression of miR-125b attenuated the promoting effects of rh-ActA on primordial follicle assembly. Taken together, these data suggest that miR-125b blocks the process of primordial follicle assembly, and miR-125b may play this role by regulating the expression ofAcvr2ain the activin/Smad2 signaling pathway.
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, People's Republic of China.
authors.forename: Shufen
authors.initials: S
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, People's Republic of China.
authors.forename: Jiali
authors.initials: J
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, People's Republic of China.
authors.forename: Xinqiang
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, People's Republic of China.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Ji
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, People's Republic of China.
authors.forename: Jianfang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, People's Republic of China cuisheng@cau.edu.cn.
authors.forename: Sheng
authors.initials: S
authors.lastname: Cui
mesh_terms: D030301:Activin Receptors, Type II / Q000378:metabolism*; D028341:Activins / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D005260:Female; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D010053:Ovary / Q000502:physiology*; D011247:Pregnancy; D051899:Smad2 Protein / Q000378:metabolism
chemical_list: D035683:MicroRNAs; C527468:Mirn125 microRNA, mouse; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D028341:Activins; D030301:Activin Receptors, Type II; C425585:activin receptor type II-A
keywords: Smad2 signaling; activin; activin receptor type 2a; miR-125b; primordial follicle assembly