Leukocytes are in situ regulators critical for ovarian function. However, little is known about leukocyte subpopulations and their interaction with follicular cells in ovulatory follicles, especially in humans. Single-cell RNA sequencing (scRNA-seq) was performed using follicular aspirates obtained from four IVF patients and identified 13 cell groups: one granulosa cell group, one thecal cell group, 10 subsets of leukocytes, and one group of RBC/platelet. RNA velocity analyses on five granulosa cell populations predicted developmental dynamics denoting two projections of differentiation states. The cell type-specific transcriptomic profiling analyses revealed the presence of a diverse array of leukocyte-derived factors that can directly impact granulosa cell function by activating their receptors (e.g., cytokines and secretory ligands) and are involved in tissue remodeling (e.g., MMPs, ADAMs, ADAMTSs, and TIMPs) and angiogenesis (e.g., VEGFs, PGF, FGF, IGF, and THBS1) in ovulatory follicles. Consistent with the findings from the scRNA-seq data, the leukocyte-specific expression of CD68, IL1B, and MMP9 was verified in follicle tissues collected before and at defined hours after hCG administration from regularly cycling women. Collectively, this study demonstrates that this data can be used as an invaluable resource for identifying important leukocyte-derived factors that promote follicular cell function, thereby facilitating ovulation and luteinization in women.
|State||Published - Apr 2023|
Bibliographical noteFunding Information:
We thank Drs. Patrick Hannon and Ketan Shrestha at the University of Kentucky College of Medicine for critical reading of the manuscript.
This research was supported by the Lalor Foundation Postdoctoral Fellowship (YC), R03HD109497 (YC), P01HD71875 (MJ, TEC, and MB), R03HD095098 (MJ), and R01HD096077 (MJ). This research was also supported by the Biospecimen and Tissue Procurement Shared Resource Facility of the University of Kentucky Markey Cancer Center (P30CA177558).
© 2023 Federation of American Societies for Experimental Biology.
- RNA velocity
- ovulatory follicles
- single-cell RNA sequencing
ASJC Scopus subject areas
- Molecular Biology