Ovarian Granulosa Cells (GCs) are known to proliferate in the developing follicle and undergo several biochemical processes during folliculogenesis. They represent a multipotent cell population that has been differentiated to neuronal cells, chondrocytes, and osteoblasts in vitro. However, progression and maturation of GCs are accompanied by a reduction in their stemness. In the developing follicle, GCs communicate with the oocyte bidirectionally via gap junctions. Together with neighboring theca cells, they play a crucial role in steroidogenesis, particularly the production of estradiol, as well as progesterone following luteinization. Many signaling pathways are known to be important throughout the follicle development, leading either towards luteinization and release of the oocyte, or follicular atresia and apoptosis. These signaling pathways include cAMP, PI3K, SMAD, Hedgehog (HH), Hippo and Notch, which act together in a complex manner to control the maturation of GCs through regulation of key genes, from the primordial follicle to the luteal phase. Small molecules such as resveratrol, a phytoalexin found in grapes, peanuts and other dietary constituents, may be able to activate/inhibit these signaling pathways and thereby control physiological properties of GCs. This article reviews the current knowledge about granulosa stem cells, the signaling pathways driving their development and maturation, as well as biological activities of resveratrol and its properties as a pro-differentiation agent.

Department of Anatomy Poznan University of Medical Sciences Swiecickiego 6 St PL 60 781 Poznan Poland

Department of Histology and Embryology Poznan University of Medical Sciences Swiecickiego 6 St PL 60 781 Poznan Poland

Department of Obstetrics and Gynecology University Hospital and Masaryk University 60200 Brno Czech Republic

Department of Toxicology Poznan University of Medical Sciences Dojazd 30 St PL 60 631 Poznan Poland

Department of Veterinary Surgery Institute of Veterinary Medicine Nicolaus Copernicus University in Torun 87 100 Torun Poland

Division of Infertility and Reproductive Endocrinology Department of Gynecology Obstetrics and Gynecological Oncology Poznan University of Medical Sciences Polna 33 St PL 60 535 Poznan Poland

Physiology Graduate Program North Carolina State University Campus Box 7608 Raleigh NC 27695 7608 USA

Radiology Lab Department of Medical Physics Greater Poland Cancer Centre Garbary 15 St PL 61 866 Poznan Poland

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