In vivo treatment with GDF-9 stimulates primordial and primary follicle progression and theca cell marker CYP17 in ovaries of immature rats.
Growth differentiation factor (GDF)-9 is a cystine knot-containing hormone of the transforming growth factor-beta superfamily produced by the oocyte. In GDF-9 null mice, follicle development is arrested at the primary stage and GDF-9 treatment in vitro enhances preantral follicle growth. Immature female rats were treated with recombinant GDF-9 for 7 or 10 days. At 10 days, treatment with GDF-9 augmented ovarian weights, concomitant with an increase in the number of primary and small preantral follicles by 30 and 60%, respectively. Furthermore, the number of primordial follicles was decreased by 29%, but the number of large preantral follicles was not affected. In contrast, treatment with FSH increased the number of small and large preantral follicles by 36 and 177% but did not influence the number of primary and primordial follicles. Immunoblot analysis showed an increase of CYP17, a theca cell marker, in the ovarian homogenate after treatment with GDF-9 but not FSH. The present results indicate that in vivo treatment with GDF-9 enhances the progression of primordial and primary follicles into small preantral follicles. Thus, GDF-9 treatment could provide an alternative approach to stimulate early follicle development in addition to the widely used FSH that acts mainly on the development of more advanced follicles.
Vitt
U A
UA
Department of Gynecology and Obstetrics, Stanford University School of Medicine, California 94305-5317, USA.
McGee
E A
EA
Hayashi
M
M
Hsueh
A J
AJ
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D015415:Biomarkers; D055430:Bone Morphogenetic Protein 15; D005260:Female; D055429:Growth Differentiation Factor 9; D006133:Growth Substances / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins; D009929:Organ Size / Q000187:drug effects; D006080:Ovarian Follicle / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D010053:Ovary / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism*; D013799:Theca Cells / Q000378:metabolism*; D013997:Time Factors
D015415:Biomarkers; C525902:Bmp15 protein, mouse; C525904:Bmp15 protein, rat; D055430:Bone Morphogenetic Protein 15; C525898:Gdf9 protein, mouse; C525899:Gdf9 protein, rat; D055429:Growth Differentiation Factor 9; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D013254:Steroid 17-alpha-Hydroxylase