Coutts Shiona M, Childs Andrew J, Fulton Norma, Collins Craig, Bayne Rosemary A L, McNeilly Alan S, Anderson Richard A
MRC Human Reproductive Sciences Unit, The Queen's Medical Research Institute, University of Edinburgh, UK.
Dev Biol. 2008 Feb 1;314(1):189-99. doi: 10.1016/j.ydbio.2007.11.026. Epub 2007 Dec 3.
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 beta 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.
卵巢生殖细胞的存活依赖于原始卵泡的形成，这一过程在人类胎儿期发生。此时，激活素有助于生殖细胞的增殖和存活。SMAD2和SMAD3是激活素信号通路的核心元件，因此指示了激活素的作用位点。我们研究了妊娠14至20周胎儿卵巢中SMAD2和SMAD3的表达及定位，即原始卵泡形成之前及形成过程中。SMAD3 mRNA表达增加了1.9倍（P = 0.02）。通过免疫荧光将SMAD2和SMAD3蛋白定位到三种不同类型的体细胞的细胞核中：（a）生殖细胞簇之间的基质细胞；（b）一些与表达激活素βA的生殖细胞混合的体细胞；（c）围绕原始卵泡的前颗粒细胞。生殖细胞不表达SMAD2或SMAD3。在体外，激活素A增加而卵泡抑素减少SMAD2/3的磷酸化，激活素增加SMAD2并降低KITLG mRNA表达。因此，在发育中的卵巢中，体细胞似乎是激活素信号的靶标。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效应。
