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Bone morphogenetic protein 15 and growth differentiation factor 9 co-operate to regulate granulosa cell function
Kenneth P McNatty1, Jennifer L Juengel, Karen L Reader
1AgResearch, Wallaceville Animal Research Centre, Ward Street, PO Box 40063, Upper Hutt, New Zealand. ken.mcnatty@agresearch.co.nz
Reproduction (Cambridge, England)
|March 31, 2005
Summary
Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) work together to regulate ovarian granulosa cell proliferation and differentiation. Their combined action synergistically enhances cell proliferation and alters hormone production, unlike their individual effects.
Area of Science:
- Reproductive Biology
- Endocrinology
- Cellular Biology
Background:
- Oocyte-secreted factors, growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15), are crucial for ovarian follicular development and function.
- Understanding the specific roles and interactions of these growth factors is essential for comprehending ovarian physiology.
Purpose of the Study:
- To investigate the individual and combined effects of murine and ovine GDF9 and ovine BMP15 on rat granulosa cell proliferation and function.
- To determine the impact of these oocyte-derived growth factors on thymidine incorporation, progesterone, and inhibin production.
Main Methods:
- Granulosa cells from rats were treated with various combinations of murine GDF9, ovine GDF9, and ovine BMP15.
- 3H-thymidine incorporation was measured to assess cell proliferation.
- Progesterone and immunoreactive alpha-inhibin levels were quantified to evaluate steroidogenesis and specific protein production.
Main Results:
- Ovine BMP15 synergistically enhanced murine GDF9- or ovine GDF9-stimulated 3H-thymidine incorporation in granulosa cells, showing a greater than 3-fold increase compared to individual factors.
- The synergistic effect of BMP15 and GDF9 on proliferation was significantly blocked by specific antibodies.
- While individual factors did not affect FSH-stimulated progesterone production, their combination potently inhibited it.
- BMP15 and GDF9 administered together markedly increased alpha-inhibin levels (over 15-fold), an effect not observed with individual factors.
Conclusions:
- Oocyte-secreted GDF9 and BMP15 exhibit synergistic effects on granulosa cell proliferation, significantly exceeding their individual impacts.
- The combination of GDF9 and BMP15 plays a critical role in regulating gonadotropin-induced differentiation, as evidenced by altered progesterone and inhibin production.
- These findings support the hypothesis that GDF9 and BMP15 cooperate within the ovary to control granulosa cell proliferation and differentiation in mammals.