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Single-Cell Transcriptomics Analysis of Human Small Antral Follicles.

Xueying Fan1, Ioannis Moustakas1,2, Monika Bialecka1

  • 1Department of Anatomy and Embryology, Leiden University Medical Center, 2333 ZC Leiden, The Netherlands.

International Journal of Molecular Sciences
|November 13, 2021
PubMed
Summary

This study reveals two distinct types of healthy small antral follicles in human ovaries, characterized by unique oocyte and granulosa cell signatures. It maps key signaling pathways crucial for ovarian follicle development.

Keywords:
antral folliclegranulosa cellhuman adult ovaryoocytesignaling pathwayssingle-cell transcriptomics

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Area of Science:

  • Reproductive Biology
  • Cellular and Molecular Biology
  • Genomics and Transcriptomics

Background:

  • Human ovarian folliculogenesis is a complex, regulated process essential for reproduction.
  • Understanding follicular cell signatures is key to determining follicle fate (growth, dominance, atresia).
  • Previous studies described transcriptomes of early and ovulatory follicles, but not small antral follicles.

Purpose of the Study:

  • To characterize the molecular signatures of oocytes and granulosa cells in human small antral follicles.
  • To identify distinct types of healthy small antral follicles.
  • To investigate intercellular communication pathways between oocytes and granulosa cells.

Main Methods:

  • Generated single-cell RNA sequencing (SmartSeq2) data from oocytes and surrounding granulosa cells of human small antral follicles.
  • Utilized the CellphoneDB algorithm to analyze ligand-receptor interactions.
  • Focused on transforming growth factor-β (TGFβ)/bone morphogenetic protein (BMP), wingless-type (MMTV)-integration site (WNT), NOTCH, and receptor tyrosine kinases (RTK) signaling pathways.

Main Results:

  • Identified two distinct types of healthy small antral follicles based on unique oocyte and granulosa cell transcriptomic signatures.
  • Revealed diverse bi-directional signaling interactions between oocytes and granulosa cells within these follicle types.
  • Detailed specific ligand-receptor interactions within key signaling pathways (TGFβ/BMP, WNT, NOTCH, RTK).

Conclusions:

  • Demonstrated significant heterogeneity among human small antral follicles.
  • Provided a detailed molecular map of oocyte-granulosa cell interactions in this critical developmental stage.
  • Contributed to filling knowledge gaps in human folliculogenesis and oogenesis molecular landscape.