Approaches for in vitro culture of granulosa cells and ovarian follicles

Abstract

The in vitro culture of ovarian follicles or cumulus-oocyte complexes (COC) is used to study the factors that regulate follicular development and may have potential use in artificial reproductive technology (ART). Before ovulation, the follicle is formed by oocyte and cell populations known as granulosa cells (GCs). These cells build the internal and external mass of the follicular wall. Oocyte growth and proliferation of the surrounding cells depend on the gap junctions between the oocyte and the GCs. Maintenance of the optimal in vitro culture system allowing for preservation of follicle architecture and granulosa-oocyte interaction may be critical for success in vitro maturation of follicles. Recently many studies have focused on a culture of GCs, which have important functions related to steroidogenesis. Granulosa cells maintained in in vitro conditions exhibit stem cell properties making it important to consider in vitro culture (IVC) methods of the GC population.

Human-induced pluripotent stem cell-derived ovarian support cell co-culture improves oocyte maturation in vitro after abbreviated gonadotropin stimulation

“…This study represents an important first step in establishing stem cell derived OSCs as a co-culture platform for IVM. This study builds on previous findings that demonstrate a benefit to using primary granulosa cell co-culture for IVM of oocytes ( Torre et al , 2006 ; Johnson et al , 2008 ; Jahromi et al , 2015 ; Zgórecka et al , 2022 ). The use of OSCs derived from hiPSCs represents a powerful approach for providing curated granulosa-like cells with characteristics more similar to a follicular, rather than luteal, phase environment, as well as providing a highly controlled and robust manner for their consistent production and qualification for broad use in clinical settings.…”

“…Many of these processes are regulated by somatic ovarian cells, such as granulosa, theca, and stroma cells. Limited but promising research has been performed to assess the use of these somatic cell types to support human oocyte IVM applications ( Torre et al , 2006 ; Johnson et al , 2008 ; Jahromi et al , 2015 ; Zgórecka et al , 2022 ). However, the use of patient-derived somatic cell types besides cumulus cells is challenging due to inconsistent cell type composition retrievals, difficulties in extracting and purifying cell populations, and the infeasibility of extracting sufficient support cells without harming patients.…”

Human induced pluripotent stem cell-derived ovarian support cell co-culture improves oocyte maturationin vitroafter abbreviated gonadotropin stimulation

“…This study builds on previous findings that demonstrate a benefit to using primary granulosa cell co-culture for in vitro maturation of oocytes. [37][38][39][40] More research is needed to determine the epigenetic health of embryos generated in OSC-IVM and commercially available IVM conditions and to determine whether OSC-IVM embryos are capable of healthy implantation, development and live birth compared to commercially available IVM systems and IVF controls. Regardless of the limitations, the use of OSCs derived from hiPSCs represents a powerful approach for providing curated granulosa-like cells with characteristics more similar to a follicular rather than the luteal phase environment, as well as providing a highly controlled and robust manner for their consistent production and qualification for broad use in clinical settings.…”

“…Limited research has been performed to assess the use of these somatic cell types for in vitro maturation, but evidence exists for their utility in human IVM applications. [37][38][39][40] However, the use of patient-derived somatic cell types besides cumulus cells is challenging due to inconsistent cell type composition retrieval, difficulty in extracting and purifying populations, and infeasibility of extracting the needed quantities of support cells without harming patients. In addition, the issue underlying some patients' infertility could reside in inappropriate signaling within and among their own follicular cells.…”