Growth Differentiation Factor-9 Promotes the Growth, Development, and Survival of Human Ovarian Follicles in Organ Culture

Abstract

Growth differentiation factor-9 (GDF-9) is a growth factor and a member of the TGFbeta superfamily that is secreted by oocytes in growing ovarian follicles. In the current study we cultured human ovarian follicles within slices of ovarian cortical tissue in the presence and absence of recombinant rat GDF-9. Ovarian tissue was obtained by biopsy during cesarean section (31 women) or gynecological laparoscopy (3 women). The mean age (+/-SD) of the women who donated tissue was 32.8 +/- 5.0 yr (range, 19-41 yr). In these biopsies a total of 900 follicles were analyzed. A significantly higher proportion of cultured primordial follicles showed growth initiation and reached the secondary stage of development in the presence of GDF-9. In serum-free cultures after 7 d, 53% of the follicles had reached the secondary stage with GDF-9 vs. 31% in the control group (P < 0.01). Follicle viability was also improved in the presence of GDF-9 after 7 d in culture (74% GDF-9 vs. 48% control), which resulted in a smaller reduction in follicle numbers due to atresia. Treatment with GDF-9 in vitro promoted the survival and progression of human follicular development to the secondary stage. This oocyte-derived factor may be essential for the development of somatic cells in early human follicles and useful in designing culture conditions for maturation of follicles and oocytes in vitro.

Quality and functionality of human ovarian tissue after cryopreservation using an original slow freezing procedure

“…Despite encouraging results regarding functionality and developmental capacity of follicles under low-attachment conditions, the increasing atresia rate suggests that conditions for in vitro culture of frozen/thawed ovarian tissues still need to be optimized. Changes in the composition of the culture medium such as a supplementation with GDF-9, BMP15 and IGF-I which have been found to improve survival rate and promote follicular growth in culture, should be considered [20,23,27].…”

Interaction between growth differentiation factor 9, insulin-like growth factor I and growth hormone on the in vitro development and survival of goat preantral follicles

“…Deletion of the GDF-9 gene in mice blocked folliculogenesis at the primary stage, demonstrating the importance of this growth factor in early follicular development (29). Subsequent studies have shown that treatment with GDF-9 stimulates granulosa cell proliferation in rats (9), preantral follicle growth in humans (30) and goats (11) and cumulus cell expansion in humans (31) and results in a higher proportion of viable human follicles in organ culture, suggesting a possible role for GDF-9 in follicular survival (10). Moreover, the presence of GDF-9 in primary and later-stage goat follicles (32) suggests that GDF-9-mediated signaling events may be important for the development of preantral follicles in this species.…”

“…Nilsson and Skinner (8) have shown that GDF-9 promotes the development of primary follicles in neonatal rat ovaries. Furthermore, recent studies have shown that GDF-9 stimulates the in vitro growth of preantral follicles and thecal cell differentiation in the rat (5,9) as well as primary and early secondary follicle formation in human ovarian slices in vitro (10). Recently, we have demonstrated that GDF-9 promotes in vitro follicular survival, growth and progression to the secondary follicle stage in goats, maintaining follicular ultrastructure (11).…”

Understanding Ovarian Life Cycle

“…Kuvvetle muhtemeldir ki overde lokal olarak üretilen baz› faktörlerin FSH ile etkileflimleri sonucu bu farkl›l›¤› yarat›yor olabilir. büyümekte olan sekonder folikül say›s›n› artt›rmaktad›r (40,(58)(59)(60) . GDF-9 geni olmayan farede folikül büyümesinin primer aflamada kalmas›da folikül büyümesinde bu büyüme faktörünün önemini göstermektedir (37,61,62) .…”