Bromodomain containing 2 (Brd2) is expressed in distinct patterns during ovarian folliculogenesis independent of FSH or GDF9 action

We previously observed high levels of Brd2 (also known as female sterile homeotic related gene-1, Fsrg1) expression in several hormonally responsive tissues, including the ovary. Here, we report distinct localization patterns of Brd2 transcripts throughout ovarian folliculogenesis in normal mice as well as in two strains of mice with aberrant folliculogenesis: mice with mutated growth differentiation factor 9 (Gdf9) and follicle stimulating hormone beta (Fshb) genes. The highest level of expression was seen in granulosa cells of growing follicles. Within the oocyte, three patterns of Brd2 RNA localization were observed: diffuse distribution in both the cytoplasm and nucleus, then intense nuclear expression, followed by an absence of Brd2 transcripts from the nucleus. The transition from intense nuclear localization to nuclear exclusion was found to correlate with oocyte maturation and meiotic competence, as determined by nuclear chromatin patterns. These same expression patterns were also seen in oocytes from Gdf9(-/-) and Fshb(-/-) mice. Thus, Brd2 expression appears to correlate with stages of oocyte maturation, independent of FSH or GDF9 action and the subsequent disruption in normal follicle development in these models. The distinct patterns of Brd2 localization within the adult ovary supports a role for Brd2 in mitotic and possibly meiotic cell cycle regulation. (C) 2004 Wiley-Liss, Inc.