Ovarian dendritic cells act as a double-edged pro-ovulatory and anti-inflammatory sword

Mol Endocrinol. 2014 Jul;28(7):1039-54. doi: 10.1210/me.2013-1400. Epub 2014 May 13.

Abstract

Ovulation and inflammation share common attributes, including immune cell invasion into the ovary. The present study aims at deciphering the role of dendritic cells (DCs) in ovulation and corpus luteum formation. Using a CD11c-EYFP transgenic mouse model, ovarian transplantation experiments, and fluorescence-activated cell sorting analyses, we demonstrate that CD11c-positive, F4/80-negative cells, representing DCs, are recruited to the ovary under gonadotropin regulation. By conditional ablation of these cells in CD11c-DTR transgenic mice, we revealed that they are essential for expansion of the cumulus-oocyte complex, release of the ovum from the ovarian follicle, formation of a functional corpus luteum, and enhanced lymphangiogenesis. These experiments were complemented by allogeneic DC transplantation after conditional ablation of CD11c-positive cells that rescued ovulation. The pro-ovulatory effects of these cells were mediated by up-regulation of ovulation-essential genes. Interestingly, we detected a remarkable anti-inflammatory capacity of ovarian DCs, which seemingly serves to restrict the ovulatory-associated inflammation. In addition to discovering the role of DCs in ovulation, this study implies the extended capabilities of these cells, beyond their classic immunologic role, which is relevant also to other biological systems.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents
  • Antigens, Differentiation / genetics
  • CD11c Antigen / biosynthesis
  • CD11c Antigen / genetics
  • Chorionic Gonadotropin / metabolism
  • Corpus Luteum / cytology*
  • Corpus Luteum / metabolism
  • Cumulus Cells / cytology
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Diphtheria Toxin / pharmacology
  • Female
  • Inflammation / genetics
  • Inflammation / immunology*
  • Lymphangiogenesis / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Oocytes / cytology
  • Ovarian Follicle / metabolism
  • Ovary / cytology
  • Ovary / transplantation
  • Ovulation / genetics
  • Ovulation / physiology*
  • Ovum / physiology
  • Progesterone / biosynthesis

Substances

  • Anti-Inflammatory Agents
  • Antigens, Differentiation
  • CD11c Antigen
  • Chorionic Gonadotropin
  • Diphtheria Toxin
  • monocyte-macrophage differentiation antigen
  • Progesterone

Grants and funding

This work was supported by the Dwek Fund for Biomedical Research (to N.D.), the Seventh Framework European Research Council (Advanced Grant 232640-IMAGO, and the Israel Science Foundation (93/07 [to M.N.] and 725/13 [to N.D.]).