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Growth differentiation factor-9 is required during early ovarian folliculogenesis
J Dong1, D F Albertini, K Nishimori
1Department of Pathology, Baylor College of Medicine, Houston, Texas 77030, USA.
Abstract:
Growth factors synthesized by ovarian somatic cells directly affect oocyte growth and function, but it is unclear whether oocyte-secreted factors play a reciprocal role in modulating somatic cell functions in vivo. During the functional analysis of members of the transforming growth factor-beta superfamily in mouse development, we have uncovered a new family member, growth differentiation factor-9 (GDF-9), which is required for ovarian folliculogenesis. GDF-9 messenger RNA is synthesized only in the oocyte from the primary one-layer follicle stage until after ovulation. Here we analyse ovaries from GDF-9-deficient female mice and demonstrate that primordial and primary one-layer follicles can be formed, but there is a block in follicular development beyond the primary one-layer follicle stage which leads to complete infertility. Oocyte growth and zona pellucida formation proceed normally, but other aspects of oocyte differentiation are compromised. Thus, GDF-9 is the first oocyte-derived growth factor required for somatic cell function in vivo.
Insights
Growth Differentiation Factor-9 (GDF-9), an oocyte-secreted factor, is crucial for ovarian folliculogenesis. Mice lacking GDF-9 show blocked follicular development and infertility, highlighting its role in somatic cell function.
Area of Science:
- Reproductive Biology
- Developmental Biology
- Endocrinology
Background:
- Ovarian somatic cells produce growth factors influencing oocyte development.
- The reciprocal role of oocyte-secreted factors on somatic cells in vivo remains largely unknown.
- The transforming growth factor-beta superfamily plays critical roles in mammalian development.
Purpose of the Study:
- To investigate the function of a novel transforming growth factor-beta superfamily member, Growth Differentiation Factor-9 (GDF-9), in mouse ovarian development.
- To determine if oocyte-secreted factors, specifically GDF-9, are essential for modulating somatic cell functions in vivo.
- To elucidate the role of GDF-9 in ovarian folliculogenesis and female fertility.
Main Methods:
- Analysis of ovaries from GDF-9-deficient female mice.
- Assessment of follicular development stages from primordial to advanced follicles.
- Evaluation of oocyte growth, zona pellucida formation, and differentiation markers.
Main Results:
- GDF-9 is synthesized exclusively by oocytes from the primary one-layer follicle stage through post-ovulation.
- GDF-9-deficient mice form primordial and primary one-layer follicles, but exhibit a developmental block thereafter.
- Complete infertility, normal oocyte growth and zona pellucida formation, but compromised oocyte differentiation observed in GDF-9 deficient mice.
Conclusions:
- GDF-9 is an essential oocyte-derived growth factor required for ovarian folliculogenesis.
- GDF-9 is indispensable for proper somatic cell function within the ovarian follicle in vivo.
- This study identifies GDF-9 as the first oocyte-secreted factor with a demonstrated requirement for somatic cell function in reproduction.