Expression of CCAAT enhancer binding protein-alpha (C/EBP alpha) in the rat ovary: implications for follicular development and ovulation.

The development of follicles from the antral to the preovulatory stage in the mammalian ovary involves both proliferation and differentiation of cells. These processes are coordinated by endocrine, paracrine, and autocrine factors in a time- and cell-specific pattern. Each stage of development is characterized by expression of specific genes the products of which are involved in different cellular processes, e.g., signal transduction (cAMP-dependent protein kinases), steroidogenesis (cytochrome P450 enzymes). At the nuclear level, the signaling pathway from external stimuli converges to modify the mechanisms of transcription factors. One such factor, CCAAT enhancer binding protein-alpha (C/EBPalpha), participates in differentiation processes of several organs, e.g., liver, adipose tissue, and gut. We have previously demonstrated that C/EBPalpha is expressed in rat ovarian follicles in a cell-, time-, and hormone-specific manner. This increase in granulosa cells was concomitant with the more differentiated phenotype. The aim of the present study was to explore the function of C/EBPalpha in the rat ovary. To achieve this, the expression of C/EBPalpha in follicular cells was attenuated in vivo by the local administration of antisense oligonucleotides (AS) into the ovarian bursa, i.e., the sac-like structure surrounding the ovary of immature rats. This administration resulted in an impaired response to subsequent injections of exogenous gonadotropins (PMSG, hCG) with an attenuated expression of C/EBPalpha protein and finally a decreased ovulation rate. Furthermore, the morphology of the AS-treated ovary was altered with large, oocyte-containing follicles at a time when ovaries exposed to sense (S) oligonucleotides demonstrated newly formed corpora lutea. AS also affected the expression of the proto-oncogene c-myc, which was elevated by this treatment. The administration of S was without effects. Thus, C/EBPalpha seems to be a necessary factor for follicular development in the rat ovary.