Human Granulosa Cells—Stemness Properties, Molecular Cross-Talk and Follicular Angiogenesis

The ovarian follicle is the basic functional unit of the ovary, comprising theca cells and granulosa cells (GCs). Two different types of GCs, mural GCs and cumulus cells (CCs), serve different functions during folliculogenesis. Mural GCs produce oestrogen during the follicular phase and progesterone after ovulation, while CCs surround the oocyte tightly and form the cumulus oophurus and corona radiata inner cell layer. CCs are also engaged in bi-directional metabolite exchange with the oocyte, as they form gap-junctions, which are crucial for both the oocyte’s proper maturation and GC proliferation. However, the function of both GCs and CCs is dependent on proper follicular angiogenesis. Aside from participating in complex molecular interplay with the oocyte, the ovarian follicular cells exhibit stem-like properties, characteristic of mesenchymal stem cells (MSCs). Both GCs and CCs remain under the influence of various miRNAs, and some of them may contribute to polycystic ovary syndrome (PCOS) or premature ovarian insufficiency (POI) occurrence. Considering increasing female fertility problems worldwide, it is of interest to develop new strategies enhancing assisted reproductive techniques. Therefore, it is important to carefully consider GCs as ovarian stem cells in terms of the cellular features and molecular pathways involved in their development and interactions as well as outline their possible application in translational medicine

Dimethyl sulfoxide inhibits spontaneous oocyte fragmentation and delays inactivation of maturation promoting factor (MPF) during the prolonged culture of ovulated murine oocytes in vitro

In this study, the effects of dimethyl sulfoxide (DMSO) on the spontaneous aging of ovulated murine oocyte were evaluated in vitro. When ovulated oocytes were cultured continuously in vitro without fertilization stimulation, they underwent several phenotypic changes, including non-activation, activation, fragmentation, and lysis. To investigate the effects of DMSO on these changes, I cultured ovulated oocytes with various concentrations of DMSO and evaluated the phenotypic changes for up to 3 days. After 3 days of culture, the frequency of oocyte fragmentation was significantly lower in oocytes treated with 2 and 4% DMSO (7 and 5%, respectively) than in control oocytes (80%). All control oocytes were activated or fragmented after 3 days of culture in vitro. However, more than 80% of the oocytes cultured with 4% DMSO for 3 days contained spindles and condensed chromosomes, although they displayed abnormal spindle structures. Next Cdk1 activity in DMSO-treated oocytes was examined. The results showed that DMSO treatment prevented the reduction in Cdk1 activity during prolonged culture. Moreover, DMSO inhibited the degradation of cyclin B. These results suggest that DMSO inhibits spontaneous oocyte fragmentation and maintains Cdk1 activity in ovulated murine oocytes during prolonged culture in vitro, possibly by inhibiting cyclin B degradation