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Oncostatin-M: A Novel Leukocyte-Derived Factor Facilitating the Ovulatory Process in the Human Ovary

ABSTRACT: Leukocytes, known as key effectors for ovulation, were found to specifically express oncostatin-M (OSM), while its receptors (OSMR and IL6ST) were abundant in granulosa cells, as shown in single-cell transcriptomics of follicular aspirates. OSM levels in the follicular fluid ranged 20.99 to 429.81 pg/ml. Increases in OSM-positive cells and OSMR and IL6ST expression were detected in ovulatory follicles post-hCG administration. Treating recombinant human OSM protein (rhOSM) to hCG-primed human granulosa/lutein cells activated signaling mediators, e.g., STATs. This treatment enabled hGLC cultures to mimic the in vivo ovulatory steroidogenesis dynamic, characterized by increased progesterone and reduced estradiol, unlike hCG alone. Additionally, rhOSM modulated gene expression associated with various ovulatory changes. This evidence suggests that leukocyte-derived OSM is a groundbreaking factor in human ovulation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE277343 | GEO | 2025/09/01

REPOSITORIES: GEO

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Project description:Determining the spatial and temporal expression of genes involved in the ovulatory pathway is critical for the understanding of the role of each estrogen receptor in the modulation of folliculogenesis and ovulation. Estrogen receptor (ER) b is highly expressed in ovarian granulosa cells and mice lacking ERb (bERKO) are subfertile due to inefficient ovulation. Previous work has focused on isolated granulosa cells or cultured follicles and while informative, provides confounding results due to the heterogeneous cell types present including granulosa, theca and oocytes and exposure to in vitro conditions. Herein, we isolated preovulatory granulosa cells from WT and ERb-null mice using laser capture microdissection to examine the genomic transcriptional response downstream of PMSG (mimicking FSH) and PMSG/hCG (mimicking LH) stimulation. This allows for a direct comparison of in vivo granulosa cells at the same stage of development from both WT and ERb-null ovaries. ERb-null granulosa cells showed altered expression of genes known to be regulated by FSH (Akap12 and Runx2) as well as not previously reported (Arnt2 and Pou5f1) in WT granulosa cells. Our analysis also identified 304 genes not previously associated with ERb in granulosa cells. LH responsive genes including Abcb1b and Fam110c show reduced expression in ERb-null granulosa cells; however novel genes including Rassf2 and Megf10 were also identified as being downstream of LH signaling in granulosa cells. Collectively, our data suggests that granulosa cells from ERb-null ovaries may not be appropriately differentiated and are unable to respond properly to gonadotropin stimulation We used microarray to compare the gene expression profiles of wiltype (WT) and Erb-null (bERKO) preovulatory granulosa cells as they respond to either PMSG or PMSG+hCG treatments. Laser microdissection was used to collect a purified population of granulosa cells only from preovulatory follicles. We chose to compre the response to PMSG or PMSG+hCG of granulosa cells collected from either WT and bERKO preovulatory follicles. We chose to collect cells 48h after mice were treated with PMSG to compare the gene expression profile ot preovulatory granulosa cells. We also studied the response of these cells to LH (or hCG) as we collected cells 4h after mice were treated with hCG (peak of transcriptional response to hCG).

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Oncostatin-M: A Novel Leukocyte-Derived Factor Facilitating the Ovulatory Process in the Human Ovary

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