Ovarian dendritic cells act as a double-edged pro-ovulatory and anti-inflammatory sword.
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.
Department of Biological Regulation (A.C.-F., A.T., N.M., Y.A., N.N., I.So., I.Sa., M.N., N.D.), Weizmann Institute of Science, Rehovot 76100, Israel; Koret School of Veterinary Medicine (T.R.), The Hebrew University of Jerusalem, Rehovot 76100, Israel; B-nano Ltd (Y.A.), Rehovot 76326, Israel; and Department of Obstetrics Gynecology and Reproductive Science (G.M.), Reproductive Immunology Unit, Yale University School of Medicine, New Haven, Connecticut 06510.
Adva
A
Cohen-Fredarow
Ari
A
Tadmor
Tal
T
Raz
Naama
N
Meterani
Yoseph
Y
Addadi
Nava
N
Nevo
Inna
I
Solomonov
Irit
I
Sagi
Gil
G
Mor
Michal
M
Neeman
Nava
N
Dekel
D000818:Animals; D000893:Anti-Inflammatory Agents; D000943:Antigens, Differentiation / Q000235:genetics; D039521:CD11c Antigen / Q000096:biosynthesis / Q000235:genetics; D006063:Chorionic Gonadotropin / Q000378:metabolism; D003338:Corpus Luteum / Q000166:cytology* / Q000378:metabolism; D054885:Cumulus Cells / Q000166:cytology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D004167:Diphtheria Toxin / Q000494:pharmacology; D005260:Female; D007249:Inflammation / Q000235:genetics / Q000276:immunology*; D042583:Lymphangiogenesis / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009865:Oocytes / Q000166:cytology; D006080:Ovarian Follicle / Q000378:metabolism; D010053:Ovary / Q000166:cytology / Q000637:transplantation; D010060:Ovulation / Q000235:genetics / Q000502:physiology*; D010063:Ovum / Q000502:physiology; D011374:Progesterone / Q000096:biosynthesis
D000893:Anti-Inflammatory Agents; D000943:Antigens, Differentiation; D039521:CD11c Antigen; D006063:Chorionic Gonadotropin; D004167:Diphtheria Toxin; C036763:monocyte-macrophage differentiation antigen; D011374:Progesterone