Tian X, Halfhill A N, Diaz F J
The Pennsylvania State University, University Park, PA 16802, USA.
Gene Expr Patterns. 2010 Feb-Mar;10(2-3):105-12. doi: 10.1016/j.gep.2010.02.003. Epub 2010 Feb 20.
SMAD signaling is essential for follicular development. The distribution of activated (phosphorylated) SMADs during folliculogenesis has not been described in detail. The present results indicate that oocytes from preantral and antral follicles contain the mRNA for the receptor regulated Smads (-1, -2, -3, -5 and -9), Smad4 (co-SMAD), and Smad6 and Smad7 (inhibitory SMADs). Levels of Smad5, Smad6 and Smad7 mRNA decreased in fully-grown oocytes compared to growing oocytes. Immunostaining for pSMAD1/5/9, pSMAD2 and pSMAD3 was evident in oocytes from primordial, primary, secondary and antral follicles. We also observed substantial staining for pSMADs in intact fully-grown oocytes from antral follicles. In granulosa cells, immunostaining for both pSMAD2/3 and pSMAD1/5/9 was apparent in preantral granulosa cells from primordial to secondary follicles. In antral follicles, immunostaining for pSMADs became more intense in the cumulus cells surrounding the oocyte. Immunostaining for pSMAD2 and pSMAD1/5/9 was also apparent in the epithelium lining of the oviduct. Clearly, oocytes, preantral granulosa cells, cumulus cells and the epithelium of the oviduct are major targets of SMAD-mediated pathways in female reproductive tissues. The finding that pSMAD pathways are active in oocytes raises new questions regarding the role of TGF-beta superfamily members in directly promoting oocyte development. The extent to which defects in pSMAD signaling in oocytes or the oviduct contribute to infertility in humans or animals remains an open question.
SMAD信号通路对卵泡发育至关重要。卵泡发生过程中活化（磷酸化）SMAD的分布尚未得到详细描述。目前的结果表明，窦前卵泡和窦卵泡的卵母细胞含有受体调节型Smads（-1、-2、-3、-5和-9）、Smad4（共SMAD）以及Smad6和Smad7（抑制性SMAD）的mRNA。与生长中的卵母细胞相比，完全成熟卵母细胞中Smad5、Smad6和Smad7 mRNA的水平降低。在原始卵泡、初级卵泡、次级卵泡和窦卵泡的卵母细胞中，pSMAD1/5/9、pSMAD2和pSMAD3的免疫染色明显。我们还观察到来自窦卵泡的完整完全成熟卵母细胞中有大量pSMADs染色。在颗粒细胞中，从原始卵泡到次级卵泡的窦前颗粒细胞中pSMAD2/3和pSMAD1/5/9的免疫染色都很明显。在窦卵泡中，围绕卵母细胞的卵丘细胞中pSMADs的免疫染色变得更强。在输卵管的上皮中，pSMAD2和pSMAD1/5/9的免疫染色也很明显。显然，卵母细胞、窦前颗粒细胞、卵丘细胞和输卵管上皮是雌性生殖组织中SMAD介导通路的主要靶点。pSMAD通路在卵母细胞中活跃这一发现，引发了关于转化生长因子-β超家族成员在直接促进卵母细胞发育中作用的新问题。卵母细胞或输卵管中pSMAD信号缺陷在多大程度上导致人类或动物不孕仍是一个悬而未决的问题。
