start-ver=1.4 cd-journal=joma no-vol=375 cd-vols= no-issue=3 article-no= start-page=743 end-page=754 dt-received= dt-revised= dt-accepted= dt-pub-year=2018 dt-pub=20181030 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Runx3 regulates folliculogenesis and steroidogenesis in granulosa cells of immature mice en-subtitle= kn-subtitle= en-abstract= kn-abstract= We previously demonstrated that female Runx3 knockout (Runx3-/-) mice were anovulatory and their uteri were atrophic and that Runx3 mRNA was expressed in granulosa cells. To clarify how Runx3 regulates folliculogenesis and ovulation, we examine the effects of Runx3 knockout on the gene expression of growth factors associated with folliculogenesis and enzymes associated with steroidogenesis. In Runx3-/- mouse ovaries, the numbers of primary and antral follicles were lower than those in wild-type (wt) mice at 3 weeks of age, indicating that the loss of Runx3 affects folliculogenesis. The expression of genes encoding activin and inhibin subunits (Inha, Inhba and Inhbb) was also decreased in ovaries from the Runx3-/- mice compared with that in wt mice. Moreover, the expression of the genes Cyp11a1 and Cyp19a1 encoding steroidogenic enzymes was also decreased. In cultured granulosa cells from 3-week-old mouse ovaries, Cyp19a1 mRNA levels were lower in Runx3-/- mice than those in wt mice. Follicle-stimulating hormone (FSH) treatment increased Cyp19a1 mRNA levels in both wt and Runx3-/- granulosa cells in culture but the mRNA level in Runx3-/- granulosa cells was lower than that in wt ones, indicating that granulosa cells could not fully function in the absence of Runx3. At 3 weeks of age, gonadotropin ƒ¿ subunit, FSHƒÀ subunit and luteinizing hormone (LH) ƒÀ subunit mRNA levels were decreased in Runx3-/- mice. These findings suggest that Runx3 plays a key role in female reproduction by regulating folliculogenesis and steroidogenesis in granulosa cells. en-copyright= kn-copyright= en-aut-name=OjimaFumiya en-aut-sei=Ojima en-aut-mei=Fumiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SaitoYuka en-aut-sei=Saito en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsuchiyaYukiko en-aut-sei=Tsuchiya en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OgoshiMaho en-aut-sei=Ogoshi en-aut-mei=Maho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FukamachiHiroshi en-aut-sei=Fukamachi en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=InagakiKenichi en-aut-sei=Inagaki en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakeuchiSakae en-aut-sei=Takeuchi en-aut-mei=Sakae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakahashiSumio en-aut-sei=Takahashi en-aut-mei=Sumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Biology, The Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Department of Biology, The Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Department of Biology, The Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Department of Biology, The Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=The Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University kn-affil= affil-num=6 en-affil=The Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=The Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Biology, The Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=9 en-affil=Department of Biology, The Graduate School of Natural Science and Technology, Okayama University kn-affil= en-keyword=Estrogen kn-keyword=Estrogen en-keyword=Follicle kn-keyword=Follicle en-keyword=Mouse kn-keyword=Mouse en-keyword=Ovary kn-keyword=Ovary en-keyword=Runx3 kn-keyword=Runx3 END