Burns Kathleen H, Owens Gabe E, Fernandez Julianna M, Nilson John H, Matzuk Martin M
Department of Pathology, Baylor College of Medicine, Houston, Texas 77030, USA.
Biol Reprod. 2002 Sep;67(3):743-51. doi: 10.1095/biolreprod.101.000729.
Integrin alpha:beta heterodimers mediate cell contacts to the extracellular matrix and initiate intracellular signaling cascades in response to a variety of factors. Integrins interact with many determinants of cellular phenotypes and play roles in controlling the development, structural integrity, and function of every type of tissue. Despite their importance, little is known about the regulation of integrin subunits in the mammalian ovary and how they function in folliculogenesis. To determine their relevance to ovarian physiology, we have studied the expression of integrin subunit mRNAs by Northern blot analysis and in situ hybridization in ovaries of wild-type, growth differentiation factor 9 (Gdf 9) knockout, FSHbeta (Fshb) knockout, and inhibin alpha (Inha) knockout mice. Integrin alpha6 mRNA is expressed in oocytes and granulosa cells of single-layer follicles and in oocytes and theca cells of multilayer follicles. Integrin alpha6 is highly expressed in Gdf 9 knockout ovaries, which are enriched in oocytes and primary (single layer) follicles because of a block at this stage of follicular development. Integrin alpha(v) mRNA is most highly expressed in the granulosa cells of multilayer growing follicles, and therefore only low levels of expression are detectable in the Gdf 9 knockout ovaries. Integrin beta1 mRNA exhibits a broad expression pattern in ovaries, including oocytes, granulosa cells, theca cells, and corpora lutea. Integrin beta3 mRNA is expressed in theca and interstitial cells and is upregulated in corpora lutea. It is nearly undetectable in ovaries of Fshb knockout mice, which develop preantral follicles but have no luteal cells. Integrin beta5 mRNA is predominantly expressed in granulosa cells of multilayer follicles. It is expressed at high levels in the Fshb knockout mice and in a compartmentalized manner in the granulosa cell/Sertoli cell tumors that develop in the Inha knockout mice. Specific integrins are associated with ovarian cellular phenotypes in mice, which raises intriguing possibilities as to integrin functions in oocyte competence, follicular development, luteinization, and granulosa cell proliferation.
整合素α:β异二聚体介导细胞与细胞外基质的接触，并响应多种因素启动细胞内信号级联反应。整合素与细胞表型的许多决定因素相互作用，并在控制各类组织的发育、结构完整性和功能中发挥作用。尽管它们很重要，但关于哺乳动物卵巢中整合素亚基的调节及其在卵泡发生中的功能却知之甚少。为了确定它们与卵巢生理学的相关性，我们通过Northern印迹分析和原位杂交研究了野生型、生长分化因子9（Gdf 9）基因敲除、FSHβ（Fshb）基因敲除和抑制素α（Inha）基因敲除小鼠卵巢中整合素亚基mRNA的表达。整合素α6 mRNA在单层卵泡的卵母细胞和颗粒细胞以及多层卵泡的卵母细胞和膜细胞中表达。整合素α6在Gdf 9基因敲除的卵巢中高度表达，由于卵泡发育在此阶段受阻，这些卵巢中富含卵母细胞和初级（单层）卵泡。整合素α(v) mRNA在多层生长卵泡的颗粒细胞中表达最高，因此在Gdf 9基因敲除的卵巢中只能检测到低水平的表达。整合素β1 mRNA在卵巢中呈现广泛的表达模式，包括卵母细胞、颗粒细胞、膜细胞和黄体。整合素β3 mRNA在膜细胞和间质细胞中表达，并在黄体中上调。在Fshb基因敲除小鼠的卵巢中几乎检测不到，这些小鼠发育出窦前卵泡但没有黄体细胞。整合素β5 mRNA主要在多层卵泡的颗粒细胞中表达。它在Fshb基因敲除小鼠中高水平表达，并以分区方式在Inha基因敲除小鼠中发生的颗粒细胞/支持细胞肿瘤中表达。特定的整合素与小鼠卵巢细胞表型相关，这为整合素在卵母细胞能力、卵泡发育、黄体化和颗粒细胞增殖中的功能带来了有趣的可能性。
