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Evolutionarily divergent transcriptomic programs in ovarian folliculogenesis across mice, monkeys and humans

ABSTRACT: Understanding the mechanisms for human ovarian folliculogenesis is fundamental to reproductive biology and medicine. Here, we investigated transcriptomic dynamics in individual oocytes and their associated granulosa cells (GCs) during folliculogenesis in mice, monkeys and humans. Unlike mouse oocytes, which exhibited stage-specific, stepwise transcriptomic maturation, monkey and human oocytes showed minimal transcriptomic changes until the secondary follicle stage and could be broadly categorized as either immature or mature. In all three species, most highly variable genes (HVGs) during oocyte growth displayed monotonic up- or downregulation, with limited overlap in HVGs across species. GCs exhibited similarly species-specific transcriptomic trajectories. Correspondingly, intercellular communication pathways, including ligand–receptor signaling, gap junctions, and metabolic coupling between oocytes and GCs, demonstrated substantial species-specific differences. Nonetheless, X-chromosome dosage compensation and repression of evolutionarily young transposons were conserved across species. We established in vitro culture systems supporting preantral to antral follicle development in monkeys and humans, revealing relatively normal oocyte transcriptome maturation but aberrant GC profiles. By delineating interspecies differences in folliculogenesis, this study provides a framework for understanding human ovarian development and advancing its in vitro reconstruction.

ORGANISM(S): Macaca fascicularis

PROVIDER: GSE290087 | GEO | 2026/01/19

REPOSITORIES: GEO

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Evolutionarily divergent transcriptomic programs in ovarian folliculogenesis across mice, monkeys and humans

Project description:Understanding the mechanisms for human ovarian folliculogenesis is fundamental to reproductive biology and medicine. Here, we investigated transcriptomic dynamics in individual oocytes and their associated granulosa cells (GCs) during folliculogenesis in mice, monkeys and humans. Unlike mouse oocytes, which exhibited stage-specific, stepwise transcriptomic maturation, monkey and human oocytes showed minimal transcriptomic changes until the secondary follicle stage and could be broadly categorized as either immature or mature. In all three species, most highly variable genes (HVGs) during oocyte growth displayed monotonic up- or downregulation, with limited overlap in HVGs across species. GCs exhibited similarly species-specific transcriptomic trajectories. Correspondingly, intercellular communication pathways, including ligand–receptor signaling, gap junctions, and metabolic coupling between oocytes and GCs, demonstrated substantial species-specific differences. Nonetheless, X-chromosome dosage compensation and repression of evolutionarily young transposons were conserved across species. We established in vitro culture systems supporting preantral to antral follicle development in monkeys and humans, revealing relatively normal oocyte transcriptome maturation but aberrant GC profiles. By delineating interspecies differences in folliculogenesis, this study provides a framework for understanding human ovarian development and advancing its in vitro reconstruction.

2026-01-19 | GSE290088 | GEO

Evolutionarily divergent transcriptomic programs in ovarian folliculogenesis across mice, monkeys and humans

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Project description:Female fertility is determined in part by the size and development of the primordial follicle pool. The current study investigates the role of glial cell-line derived neurotrophic factor (GDNF) in the regulation of primordial follicle development in the ovary. Ovaries from four-day old female rat pups were maintained in organ culture for ten days in the absence (control) or presence of GDNF or kit ligand/stem cell factor (KL). Ovaries treated with GDNF contained a significant increase in developing follicles, similar to that observed with KL treatment previously shown to promote follicle development. The actions of GDNF on the ovarian transcriptome were investigated with a microarray analysis. Immunohistochemical studies demonstrated that GDNF is localized to oocyte cytoplasm in follicles of all developmental stages, as well as to cumulus granulosa cells and theca cells in antral follicles. GDNF receptor alpha 1 (GFRalpha1) staining was localized to oocyte cytoplasm of primordial and primary follicles, and at reduced levels in oocytes of antral follicles. GFRalpha1 was present in mural granulosa cells of antral follicles, theca cells, and the ovarian surface epithelium. The localization studies were confirmed with molecular analysis. Microarray analysis was used to identify changes in the ovarian transcriptome and further elucidate the signaling network regulating early follicle development. Observations indicate that GDNF promotes primordial follicle development and mediates autocrine and paracrine cell-cell interactions required during folliculogenesis. In contrast to the testis, ovarian GDNF is predominantly produced by germ cells (oocytes) rather than somatic cells. Experiment Overall Design: RNA samples from two control groups (pooled untreated cultured ovaries) are compared to two treated groups (pooled cultured ovaries treated with GDNF)

2008-06-11 | E-GEOD-11133 | biostudies-arrayexpress

Glial derived neurotrophic factor promotes ovarian primordial follicle development during folliculogenesis

Project description:Female fertility is determined in part by the size and development of the primordial follicle pool. The current study investigates the role of glial cell-line derived neurotrophic factor (GDNF) in the regulation of primordial follicle development in the ovary. Ovaries from four-day old female rat pups were maintained in organ culture for ten days in the absence (control) or presence of GDNF or kit ligand/stem cell factor (KL). Ovaries treated with GDNF contained a significant increase in developing follicles, similar to that observed with KL treatment previously shown to promote follicle development. The actions of GDNF on the ovarian transcriptome were investigated with a microarray analysis. Immunohistochemical studies demonstrated that GDNF is localized to oocyte cytoplasm in follicles of all developmental stages, as well as to cumulus granulosa cells and theca cells in antral follicles. GDNF receptor alpha 1 (GFRalpha1) staining was localized to oocyte cytoplasm of primordial and primary follicles, and at reduced levels in oocytes of antral follicles. GFRalpha1 was present in mural granulosa cells of antral follicles, theca cells, and the ovarian surface epithelium. The localization studies were confirmed with molecular analysis. Microarray analysis was used to identify changes in the ovarian transcriptome and further elucidate the signaling network regulating early follicle development. Observations indicate that GDNF promotes primordial follicle development and mediates autocrine and paracrine cell-cell interactions required during folliculogenesis. In contrast to the testis, ovarian GDNF is predominantly produced by germ cells (oocytes) rather than somatic cells. Keywords: expression analysis, glial derived neurotrophic factor, follicle transition, ovary

2008-04-11 | GSE11133 | GEO

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