Gonadotropin stimulation in mice leads to ovarian accumulation of immature myeloid cells and altered expression of proangiogenic genes

N. Pencovich, S. Hantisteanu, M. Hallak, O. Fainaru

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: Ovarian hyperstimulation syndrome is associated with increased angiogenesis and vascular leakage. Immature myeloid cells (IMCs) and dendritic cells have been shown to be actively involved in angiogenesis in several disease models in mice and humans. Nevertheless, little is known about the role of these cells in the ovary. As such, this study sought to determine whether alterations in these ovarian myeloid cell populations are associated with gonadotropin stimulation in a mouse model. Study design: Four-week-old pre-pubertal C57Bl/6 female mice were allocated into three groups: high-dose stimulation (n = 4; pregnant mare serum gonadotropins (PMSG) 20 U for 2 days), low-dose stimulation (n = 5; PMSG 5 U for 1 day) and sham-treated controls (n = 4). Human chorionic gonadotropin 5 U was injected on Day 3, and the mice were killed on Day 5. Ovaries were analysed by flow cytometry, confocal microscopy and quantitative polymerase chain reaction. Results: Gonadotropin stimulation increased the proportion of CD11b + Gr1 + IMCs among the ovarian myeloid cells: 22.6 ± 8.1% (high dose), 7.2 ± 1.6% (low dose) and 4.1 ± 0.3% (control) (p = 0.02). Conversely, gonadotropin stimulation decreased the proportion of ovarian CD11c + MHCII + dendritic cells: 15.1 ± 1.9% (high dose), 20.7 ± 4.8% (low dose) and 27.3 ± 8.2% (control) (p = 0.02). IMCs, unlike dendritic cells, were localized adjacent to PECAM1 + endothelial cells. Finally, gonadotropin stimulation was associated with increased expression of S100A8, S100A9, Vcan and Dmbt1, and decreased expression of MMP12. Conclusions: Gonadotropin stimulation is associated with proangiogenic myeloid cell alterations, reflected by a dose-dependent increase in ovarian IMCs and a parallel decrease in dendritic cells. Recruited IMCs localize strategically at sites of angiogenesis. These changes are associated with differential expression of key proangiogenic genes.

Original languageEnglish
Pages (from-to)75-82
Number of pages8
JournalEuropean Journal of Obstetrics, Gynecology and Reproductive Biology
Volume179
DOIs
StatePublished - Aug 2014
Externally publishedYes

Keywords

  • Angiogenesis
  • Dendritic cells
  • Immature myeloid cells
  • Ovarian stimulation

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