Activin signals via SMAD2/3 between germ and somatic cells in the human. fetal ovary and regulates kit ligand expression
Activin signals via SMAD2/3 between germ and somatic cells in the human. fetal ovary and regulates kit ligand expression
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DOI：
10.1016/j.ydbio.2007.11.026
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发表时间：
2008-02-01
影响因子：
2.7
通讯作者：
Anderson, Richard A.
中科院分区：
文献类型：
--
作者：
Coutts, Shiona M.;Childs, Andrew J.;Anderson, Richard A.
卵巢生殖细胞的存活依赖于原始卵泡的形成，原始卵泡发生在人类胎儿期。此时激活素有助于生殖细胞增殖和存活。SMAD 2和SMAD 3是激活素信号通路中的中心元件，因此指示激活素作用的位点。我们研究了SMADs 2和3在妊娠14至20周的胎儿卵巢中的表达和定位，即在原始卵泡形成之前和期间。SMAD 3 mRNA表达增加1.9倍（P=0.02）。通过免疫荧光将SMAD 2和3蛋白定位于三种不同体细胞群体的细胞核：（a）生殖细胞簇之间的基质细胞;（B）一些体细胞与表达激活素A的生殖细胞混合;（c）原始卵泡周围的前颗粒细胞。生殖细胞不表达SMAD 2或3。激活素A在体外增加SMAD 2/3的磷酸化，卵泡抑素减少SMAD 2/3的磷酸化，激活素增加SMAD 2和减少KITLG mRNA的表达。因此，体细胞似乎是卵巢发育中激活素信号传导的靶点。激活素对生殖细胞的作用是间接的，包括通过kit配体/c-Kit途径介导，而不是自分泌生殖细胞作用。(C)2007年爱思唯尔公司All rights reserved.
Ovarian germ cell survival is dependent upon the formation of primordial follicles, which occurs during fetal life in the human. Activin contributes to germ cell proliferation and survival at this time. SMADs2 and 3 are central elements in the activin signalling pathway and thus indicate sites of activin action. We have investigated the expression and localisation of SMADs2 and 3 in the fetal ovary between 14 and 20 weeks gestation, i.e. preceding and during primordial follicle formation. SMAD3 mRNA expression increased 1.9 fold (P=0.02). SMAD2 and 3 proteins were localised by immunofluorescence to the nuclei of three distinct populations of somatic cells: (a) stromal cells between clusters of germ cells; (b) some somatic cells intermingled with activin A-expressing germ cells; (c) pre-granulosa cells surrounding primordial follicles. Germ cells did not express SMAD2 or 3. Activin A increased and follistatin decreased phosphorylation of SMAD2/3 in vitro, and activin increased SMAD2 and decreased KITLG mRNA expression. It therefore appears that somatic cells are the targets for activin signalling in the developing ovary. The effects of activin on germ cells are indirect and include mediation by the kit ligand/c-Kit pathway, rather than being an autocrine germ cell effect. (C) 2007 Elsevier Inc. All rights reserved.