Interaction between growing oocytes and granulosa cells in vitro.

Md Hasanur Alam,Takashi Miyano

doi:10.1002/rmb2.12292

Abstract

BackgroundOocyte growth is accompanied by follicular development in mammalian ovaries. Since the discovery of two oocyte‐derived factors, growth differentiation factor 9 (GDF9), and bone morphogenetic protein 15 (BMP15), knowledge of the bidirectional communication between oocytes and granulosa cells for ovarian function and fertility has been accumulated. In addition, the growth culture system of oocytes has been improved, further promoting the studies on the communication between oocytes and granulosa cells in vitro.MethodsWe provide an overview of the role of granulosa cells in oocyte growth and the role of oocytes in follicular development along with our recent findings in culture experiments of bovine growing oocytes.Main findingsGranulosa cells supply nutrients and metabolites through gap junctions to oocytes and secrete paracrine signals to regulate oocytes. Oocytes regulate granulosa cell proliferation and differentiation and induce antrum formation via GDF9 and BMP15.ConclusionOocytes actively participate in various aspects of follicular development, including antrum formation via the oocyte‐derived factors GDF9 and BMP15, whose synthesis is probably regulated by granulosa cells. In vitro studies will reveal the precise communication loop between oocytes and granulosa cells that facilitates the coordinated development of oocytes and granulosa cells in the follicles.

Highlights

Mammalian oogenesis starts at the embryonic period, and primor‐ dial germ cells (PGCs) are the primary cells in the process (Figure 1)
Granulosa cells change their morphology during in vitro culture. They showed a fi‐ broblast‐like appearance in the culture dish. This transformation of Recently, we examined the effects of growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) on the morphology of cultured bovine growing oocyte‐granulosa cell complexes (OGCs).[127]
The mechanism connecting increased cAMP/cGMP with increased expression of GDF9 and BMP15 mRNAs has not been elucidated, the phosphodiesterase 3 (PDE3) inhibition probably leads to synthesis of GDF9 and BMP15 by the oocyte, with the growth factors in turn promoting the formation of antrum‐like structures by granulosa cells (Figure 2)

Summary

Introduction

Mammalian oogenesis starts at the embryonic period, and primor‐ dial germ cells (PGCs) are the primary cells in the process (Figure 1). Once the oocytes start to grow, granulosa cells change their morphology from a flattened to cuboidal shape and proliferate throughout the subsequent follicular development.[3] It is well known that proliferation of granulosa cells is stimulated by FSH and estradiol 17β in vivo and in vitro.[120] It was demonstrated in culture experiments that mouse oocytes stim‐ ulate the proliferation of granulosa cells from preantral follicles and the proliferation of more differentiated cumulus and mural granu‐ losa cells from antral follicles.[121] As expected from the phenotype in GDF9‐knockout mice, whose folliculogenesis was retarded,[20] GDF9 is one of the factors for proliferation of granulosa cells.[112] Recent studies using recombinant GDF9 and BMP15 have shown that these growth factors stimulate proliferation of cultured granulosa cells in rats,[122,123] sheep,[124] and cattle.[124]

Results

Conclusion