# The Impact of Leukocyte-Derived OSM on Ovulation and Luteinization in the Human Ovary

> **NIH NIH R03** · UNIVERSITY OF KENTUCKY · 2022 · $76,500

## Abstract

ABSTRACTS
 The ovulatory process is the mid-cycle gonadotropin surge-induced acute inflammatory response.
Leukocytes are critical effectors in the inflammatory response. However, the mechanisms of leukocyte
recruitment and the specific roles of leukocytes in the ovulatory follicle remain elusive, especially in humans.
The current study proposes to elucidate how the mid-cycle LH surge coordinates leukocyte recruitment and the
expression of genes in preovulatory follicular cells to bring about successful ovulation and luteinization in the
human ovary.
 From our pilot single-cell transcriptome analyses using human follicular aspirates from women
undergoing in vitro fertilization, we discovered that OSM (oncostatin-M) is exclusively expressed in specific
types of leukocytes, whereas its receptors, OSMR and LIFR (leukemia inhibitory factor receptor) and their co-
receptor, IL6ST (IL6 family signal transducer) are present predominantly in granulosa cells. Similarly, in
granulosa cells of dominant follicles collected from normally cycling women throughout the periovulatory
period, we found that OSMR mRNA levels were markedly increased after hCG stimulation. In addition, our
preliminary data showed that hCG increased the expression of OSM receptors, OSMR and IL6ST in primary
human granulosa cell cultures, mimicking in vivo up-regulation of OSMR. Our preliminary data also revealed
that OSM could activate specific signaling pathways and stimulate progesterone and prostaglandin E2
production, two crucial mediators of ovulation.
 Based on these novel data, we hypothesized that 1) the LH surge induces the recruitment of OSM-
expressing leukocytes, while increasing the expression of its receptors (OSMR, LIFR, IL6ST) in follicular cells
of preovulatory follicles, and 2) leukocyte-derived OSM, upon binding to its receptors in preovulatory follicular
cells, activates specific signaling pathways, and regulates the expression of specific ovulatory genes, thereby
promoting necessary ovulatory changes. These hypotheses will be tested by first characterizing expression
profiles of OSM in leukocytes and its receptors, OSMR, LIFR, and IL6ST in follicular cells of the dominant
follicles collected throughout the periovulatory period and examining the regulatory mechanisms involved in the
expression of OSM receptors in human granulosa cells (Specific Aim 1). Next, we will delineate OSM-
activated intracellular signaling pathways in human granulosa cells (Specific Aim 2). Lastly, we will elucidate
the impact of leukocyte-derived OSM on the periovulatory process by identifying OSM-regulated downstream
genes (RNA-seq analysis) and evaluating cellular/biological impacts on affected pathways using human
granulosa cell cultures. The proposed study will demonstrate “for the first time” OSM as a novel ovulatory
factor of leukocyte-origin and identify its specific roles in the human ovary, thus filling the gap in our
understahopteanding of the role of leukocytes in the ovulatory pr...

## Key facts

- **NIH application ID:** 10508652
- **Project number:** 1R03HD109497-01
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Yohan Choi
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $76,500
- **Award type:** 1
- **Project period:** 2022-08-15 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10508652

## Citation

> US National Institutes of Health, RePORTER application 10508652, The Impact of Leukocyte-Derived OSM on Ovulation and Luteinization in the Human Ovary (1R03HD109497-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10508652. Licensed CC0.

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