Human Seminal Extracellular Vesicles Enhance Endometrial Receptivity Through Leukemia Inhibitory Factor

Endocrinology. 2024 Mar 29;165(5):bqae035. doi: 10.1210/endocr/bqae035.

Abstract

Seminal extracellular vesicles (EVs) contain different subgroups that have diverse effects on sperm function. However, the effect of seminal EVs-especially their subgroups-on endometrial receptivity is largely unknown. Here, we found that seminal EVs could be divided into high-density EVs (EV-H), medium density EVs, and low-density EVs after purification using iodixanol. We demonstrated that EV-H could promote the expression and secretion of leukemia inhibitor factor (LIF) in human endometrial cells. In EV-H-treated endometrial cells, we identified 1274 differentially expressed genes (DEGs). DEGs were enriched in cell adhesion and AKT and STAT3 pathways. Therefore, we illustrated that EV-H enhanced the adhesion of human choriocarcinoma JAr cell spheroids to endometrial cells through the LIF-STAT3 pathway. Collectively, our findings indicated that seminal EV-H could regulate endometrial receptivity through the LIF pathway, which could provide novel insights into male fertility.

Keywords: LIF; adhesion; endometrial receptivity; integrin; seminal extracellular vesicles.

MeSH terms

  • Cell Adhesion / physiology
  • Embryo Implantation* / physiology
  • Endometrium / metabolism
  • Extracellular Vesicles* / metabolism
  • Female
  • Humans
  • Leukemia Inhibitory Factor / metabolism
  • Male
  • Pregnancy
  • Semen / metabolism

Substances

  • Leukemia Inhibitory Factor
  • LIF protein, human