Granulosa Cell Biology in Ovarian Follicle Development

Granulosa cells are the principal somatic cells of the ovarian follicle, providing structural support, nutrient transfer and paracrine signals to the oocyte. Throughout folliculogenesis these cells proliferate and differentiate under the influence of follicle‐stimulating hormone and local growth factors, orchestrating steroidogenesis and the transition of follicles from the primordial to preovulatory stages. They secrete oestrogens and progesterone via activation of steroidogenic acute regulatory protein and cytochrome P450 enzymes, and respond dynamically to members of the TGF-β superfamily, epidermal growth factor-like ligands and Notch signals. These interactions regulate follicle recruitment, selection, atresia and luteinisation, thereby determining reproductive potential and endocrine balance. Dysregulation of granulosa cell function underlies conditions such as premature ovarian insufficiency, polycystic ovary syndrome and subfertility.

Research from Nature Portfolio

Recent studies have clarified how luteinising hormone receptor activation triggers granulosa cell steroidogenesis. One foundational investigation revealed that amphiregulin, induced by human chorionic gonadotropin, engages the epidermal growth factor receptor and downstream ERK1/2 signalling to up-regulate steroidogenic acute regulatory protein expression, thereby increasing progesterone output. Blocking amphiregulin or EGFR ablates this effect, underscoring its pivotal role in luteal phase support. Another seminal work identified bone morphogenetic protein 2 as a key driver of primordial follicle assembly. In ex vivo ovarian cultures, BMP2 enhanced the transition of germ cells to oocytes and somatic precursors to flattened pregranulosa cells via ALK2/3 receptors. This effect reduced apoptosis and expanded the pool of nascent follicles, highlighting early granulosa cell commitment mechanisms.

Granulosa Cell Biology in Ovarian Follicle Development publication trend

The graph below shows the total number of articles in granulosa cell biology in ovarian follicle development across all publications each year (not limited to Nature Index journals).

Technical terms

Granulosa cell: Somatic ovarian cell type surrounding the oocyte, essential for its nourishment, hormonal support and paracrine communication.

Folliculogenesis: The sequence of stages by which ovarian follicles develop from primordial to preovulatory stages, involving cell proliferation, differentiation and steroidogenesis.

Steroidogenesis: Biosynthesis of steroid hormones, notably oestradiol and progesterone, by granulosa and luteal cells under gonadotropin control.

Paracrine signalling: Local cell communication via secreted factors, permitting cross-talk between oocyte, granulosa, theca and stromal cells.

Primordial follicle: The earliest follicle stage, consisting of a primary oocyte surrounded by a single layer of flattened granulosa cells.

References

1. YTHDF2 as a Mediator in BDNF-Induced Proliferation of Porcine Follicular Granulosa Cells. International Journal of Molecular Sciences (2024).
2. Amphiregulin mediates hCG-induced StAR expression and progesterone production in human granulosa cells. Scientific Reports (2016).
3. Bone morphogenetic protein 2 promotes primordial follicle formation in the ovary. Scientific Reports (2015).
4. TGF-β1 Increases GDNF Production by Upregulating the Expression of GDNF and Furin in Human Granulosa-Lutein Cells. Cells (2020).