Abstract
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.
Highlights
Resveratrol, a naturally occurring polyphenol, was initially isolated from the roots of white hellebore (Veratrum grandiflorum)
Low concentration of resveratrol stimulated thymidine incorporation [99]. Summarizing, these findings suggest that resveratrol, through activation of SIRT-1 and ERK1/2 signaling pathways, might inhibit apoptosis in the ovarian Granulosa Cells (GCs)
It has been revealed that resveratrol protects granulosa cells from degeneration, and simultaneously enhances proliferation and differentiation of
Summary
Resveratrol, a naturally occurring polyphenol, was initially isolated from the roots of white hellebore (Veratrum grandiflorum). Based on previously conducted studies, granulosa cells (GCs) are considered to possess stem cell characteristics [7,8]. They have been reported to transdifferentiate into osteoblasts and chondroblasts in the presence of leukaemia-inhibiting factor (LIF) or follicle stimulating hormone (FSH) [9,10,11]. In the light of these findings, resveratrol and/or its analogs might influence the differentiation of GCs. Recently, the therapeutic potential of mesenchymal cells has been extensively studied. 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, including its properties as a pro-differentiation agent
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