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Regular Article |
a Departments of Pathology,
b Molecular and Human Genetics, and
c Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030
d Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio 44106
Integrin 
:ß 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, FSHß (Fshb) knockout, and inhibin (Inha) knockout mice. Integrin 6 mRNA is expressed in oocytes and granulosa cells of single-layer follicles and in oocytes and theca cells of multilayer follicles. Integrin 6 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 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 ß1 mRNA exhibits a broad expression pattern in ovaries, including oocytes, granulosa cells, theca cells, and corpora lutea. Integrin ß3 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 ß5 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.
1 This work was supported by NIH grants CA 60651 and HD 33438 (M.M.M.), as well as CA086387 (J.H.N.). K.H.B. is a student in the Medical Scientist Training Program and is supported in part by NIH grant T32GM07330 and by grant T32EY07102 from the National Eye Institute. G.E.O. is a student in the Medical Scientist Training Program supported by T32GM007250.
2 Correspondence: Martin M. Matzuk, Department of Pathology, One Baylor Plaza, Baylor College of Medicine, Houston, TX 77030.FAX: 713 798 5833; mmatzuk{at}bcm.tmc.edu
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