Molecular Cloning of the Ovine Growth/Differentiation Factor-9 Gene and Expression of Growth/Differentiation Factor-9 in Ovine and Bovine Ovaries1

Bodensteiner, Karin J.; Clay, Colin M.; Moeller, C L; Sawyer, H. R.

doi:10.1095/biolreprod60.2.381

Cited by 219 publications

(130 citation statements)

References 25 publications

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“…In sheep and cows, GDF9 mRNA and/or protein is present in oocytes of most, if not all, follicles at all stages of growth including primordial follicles (Bodensteiner et al 1999). The present results are consistent with the notion that GDF9 alone may not be mitogenic in ruminant granulosa cells.…”

Section: Discussionsupporting

confidence: 90%

Bone morphogenetic protein 15 and growth differentiation factor 9 co-operate to regulate granulosa cell function in ruminants

McNatty

Juengel²,

Reader³

et al. 2005

Reproduction

191

136

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The oocyte-secreted polypeptide growth factors, growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15, also known as GDF9B) have both been shown to be essential for ovarian follicular development and ovulation rate. In addition, it is known from both in vivo and in vitro studies that these factors co-operate in some manner. To date, most studies examining the in vitro effects of these growth factors have used the rodent model. However, the evidence suggests that these growth factors have somewhat different roles between rodents and ruminants. Therefore, the objectives of these studies were to examine the effects of GDF9 and BMP15, alone and together, on the functions of ovine and bovine granulosa cells under in vitro conditions. Ovine (o)BMP15 given together with murine (m)GDF9 or oGDF9 was more potent in stimulating 3 H-thymidine incorporation by ovine granulosa cells compared with each growth factor alone. For bovine granulosa cells, there appeared to be little or no co-operativity between oBMP15 and oGDF9 as oBMP15 alone was as potent as any combination of the two growth factors in stimulating 3 H-thymidine uptake. The species of origin of GDF9 affected the progesterone response in ovine granulosa cells with mGDF9 stimulating and oGDF9 inhibiting progesterone production. Ovine BMP15 alone had no effect on progesterone production by ovine granulosa cells and these growth factors did not appear to co-operate. FSH-stimulated progesterone production by bovine granulosa cells was most potently inhibited when oBMP15 and murine or ovine GDF9 were administered together. As was observed for progesterone, the species of origin of GDF9 affected inhibin production by ovine granulosa cells where mGDF9 inhibited while oGDF9 stimulated production. Murine GDF9 also inhibited inhibin production from bovine granulosa cells. For both ovine and bovine granulosa cells, BMP15 alone had no effect on inhibin production and there did not appear to be any co-operation between GDF9 and BMP15. These results indicate that the effects of BMP15 and GDF9 varied with respect to the species of origin of the growth factor. Moreover, the effects of GDF9 and BMP15 together were often co-operative and not always the same as those observed for these growth factors alone.Reproduction (

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Section: Discussionsupporting

confidence: 90%

Bone morphogenetic protein 15 and growth differentiation factor 9 co-operate to regulate granulosa cell function in ruminants

McNatty

Juengel²,

Reader³

et al. 2005

Reproduction

191

136

View full text Add to dashboard Cite

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“…Both GDF9 mRNA and protein are present in normal sheep oocytes in non-growing type 1 follicles (i.e. primordial follicles) as well as in growing follicles [3,12] (Fig. 1).…”

Section: Intraovarian Sites Of Bmp15 and Gdf9 Gene Expression And Posmentioning

confidence: 99%

“…S31 preantral) stage of growth. It is worth noting that GDF9 mRNA and protein are present before follicular formation in sheep as well as in non-growing type 1 follicles in several species including sheep, cows and possum [3,8,12]. Thus, either the form of the protein is biologically inactive, the appropriate receptors are not present on the adjacent granulosa cells in type 1 follicles or that GDF9 is a relatively inactive growth factor when other companion factors are absent.…”

Section: Intraovarian Sites Of Bmp15 and Gdf9 Gene Expression And Posmentioning

confidence: 99%

Physiological effects of major genes affecting ovulation rate in sheep

et al. 2005

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-Genetic mutations with major effects on ovulation rate in sheep were recently identified in two genes of the transforming growth factor (TGFβ) superfamily and a TGFβ receptor, namely bone morphogenetic protein 15 (BMP15), otherwise known as the growth differentiation factor 9b (GDF9b), GDF9 and activin-like kinase 6 (ALK6) otherwise known as the BMP receptor type IB (BMPRIB). Animals homozygous for the BMP15 or GDF9 mutations are anovulatory whereas animals heterozygous for BMP15 or GDF9 or heterozygous or homozygous for ALK6 have higher than normal ovulation rates. Immunisation of ewes against BMP15 or GDF9 shows that both are essential for normal follicular development and control of ovulation rate. Common features of fertile animals with the BMP15, ALK6 (and possibly GDF9) mutations are changes in oocyte development during early preantral follicular growth, earlier maturation of granulosa cells and ovulation of mature follicles at smaller diameters. In summary, these findings have led to a new paradigm in reproductive biology, namely that the oocyte plays a key role in regulating the ovulation rate. genetic mutations / BMP15 / GDF9 / ALK6 / BMPR-IB

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“…However, in cows and pigs, expression of GDF-9 is low in oocytes of primordial follicles (Bodensteiner et al, 1999), and in humans, GDF-9 precedes the expression of BMP-15 (Aaltonen et al, 1999). In all subsequent steps of folliculogenesis, both BMP-15 and GDF-9 are present (Elvin et al, 2000).…”

Section: Folliculogenesismentioning

confidence: 99%

Regulation of ovarian function by the TGF-beta superfamily and follistatin

et al. 2003

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The role of follistatin as an activin-binding protein has dominated the study of this molecule for the last 10 years. However, there is emerging evidence that follistatin has a role in modulating the biology of other members of the transforming growth factor beta (TGF-beta) superfamily. This review summarizes the current concepts encompassing follistatin biochemistry as well as molecules with which it is functionally associated. Moreover, the importance of the two follistatin isoforms (follistatin-288 and follistatin-315) is discussed with particular emphasis on the regulation of the ovary. In addition to activin, this review discusses the functions of other members of the TGF-beta superfamily, for example growth differentiation factor 9 (GDF-9), bone morphogenetic protein 15 (BMP-15), BMP-6, BMP-4 and BMP-7, in the ovary, and the potential interactions between follistatin and these growth factors. The complex network of TGF-beta superfamily growth factor members involved in the modulation of ovarian function and the interactions of follistatin with these proteins is highlighted.

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Molecular Cloning of the Ovine Growth/Differentiation Factor-9 Gene and Expression of Growth/Differentiation Factor-9 in Ovine and Bovine Ovaries1

Cited by 219 publications

References 25 publications

Bone morphogenetic protein 15 and growth differentiation factor 9 co-operate to regulate granulosa cell function in ruminants

Bone morphogenetic protein 15 and growth differentiation factor 9 co-operate to regulate granulosa cell function in ruminants

Physiological effects of major genes affecting ovulation rate in sheep

Regulation of ovarian function by the TGF-beta superfamily and follistatin

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