Corticotropin-releasing hormone promotes blastocyst implantation and early maternal tolerance.
The semi-allograft embryo in the blastocyst stage implants itself in the endometrium, yet no immune rejection processes are activated. Embryonic trophoblast and maternal decidua produce corticotropin-releasing hormone (CRH) and express Fas ligand (FasL), a proapoptotic cytokine. We found that antalarmin, a CRH receptor type 1 antagonist, decreased FasL expression and promoted apoptosis of activated T lymphocytes, an effect which was potentiated by CRH and inhibited by antalarmin. Female rats treated with antalarmin showed a marked decrease in implantation sites and live embryos and diminished endometrial FasL expression. Embryos from mothers that lacked T cells or from syngeneic matings were not rejected when the mothers were given antalarmin. These findings suggested that locally produced CRH promotes implantation and maintenance of early pregnancy primarily by killing activated T cells.
Makrigiannakis
A
A
School of Medicine, University of Crete, Heraklion 71110, Greece. makrigia@med.uoc.gr
Zoumakis
E
E
Kalantaridou
S
S
Coutifaris
C
C
Margioris
A N
AN
Coukos
G
G
Rice
K C
KC
Gravanis
A
A
Chrousos
G P
GP
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001755:Blastocyst / Q000276:immunology / Q000502:physiology*; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology / Q000502:physiology*; D003656:Decidua / Q000276:immunology; D010064:Embryo Implantation / Q000187:drug effects / Q000502:physiology*; D004717:Endometrium / Q000276:immunology / Q000378:metabolism*; D053222:Fas Ligand Protein; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006648:Histocompatibility; D006801:Humans; D007249:Inflammation; D008098:Litter Size / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D011247:Pregnancy; D011743:Pyrimidines / Q000494:pharmacology / Q000633:toxicity; D011758:Pyrroles / Q000494:pharmacology / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344; D011923:Rats, Nude; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D014327:Trophoblasts / Q000276:immunology; D019014:fas Receptor / Q000502:physiology
C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D008562:Membrane Glycoproteins; D011743:Pyrimidines; D011758:Pyrroles; D018019:Receptors, Corticotropin-Releasing Hormone; C103016:antalarmin; D019014:fas Receptor; D003346:Corticotropin-Releasing Hormone