Regulation of fibrillins and modulators of TGFβ in fetal bovine and human ovaries

Fibrillins 1–3 are stromal extracellular matrix proteins that play important roles in regulating TGFβ activity, which stimulates fibroblasts to proliferate and synthesize collagen. In the developing ovary, the action of stroma is initially necessary for the formation of ovigerous cords and subsequently for the formation of follicles and the surface epithelium of the ovary.FBN3is highly expressed only in early ovarian development and then it declines. In contrast,FBN1and2are upregulated in later ovarian development. We examined the expression ofFBN1–3in bovine and human fetal ovaries. We used cell dispersion and monolayer culture, cell passaging and tissue culture. Cells were treated with growth factors, hormones or inhibitors to assess the regulation of expression ofFBN1–3. When bovine fetal ovarian tissue was cultured,FBN3expression declined significantly. Treatment with TGFβ-1 increasedFBN1andFBN2expression in bovine fibroblasts, but did not affectFBN3expression. Additionally, in cultures of human fetal ovarian fibroblasts (9–17weeks gestational age), the expression ofFBN1andFBN2increased with passage, whereasFBN3dramatically decreased. Treatment with activin A and a TGFβ family signaling inhibitor, SB431542, differentially regulated the expression of a range of modulators of TGFβ signaling and of other growth factors in cultured human fetal ovarian fibroblasts suggesting that TGFβ signaling is differentially involved in the regulation of ovarian fibroblasts. Additionally, since the changes inFBN1–3expression that occurin vitroare those that occur with increasing gestational agein vivo, we suggest that the fetal ovarian fibroblasts maturein vitro.