title: Ovarian insufficiency and early pregnancy loss induced by activation of the innate immune system.
abstract: We describe a murine model of early pregnancy failure induced by systemic activation of the CD40 immune costimulatory pathway. Although fetal loss involved an NK cell intermediate, it was not due to lymphocyte-mediated destruction of the fetus and placenta. Rather, pregnancy failure resulted from impaired progesterone synthesis by the corpus luteum of the ovary, an endocrine defect in turn associated with ovarian resistance to the gonadotropic effects of prolactin. Pregnancy failure also required the proinflammatory cytokine TNF-alpha and correlated with the luteal induction of the prolactin receptor signaling inhibitors suppressor of cytokine signaling 1 (Socs1) and Socs3. Such links between immune activation and reproductive endocrine dysfunction may be relevant to pregnancy loss and other clinical disorders of reproduction.
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA. aerlebac@hsph.harvard.edu
authors.forename: Adrian
authors.initials: A
authors.lastname: Erlebacher
authors.forename: Dorothy
authors.initials: D
authors.lastname: Zhang
authors.forename: Albert F
authors.initials: AF
authors.lastname: Parlow
authors.forename: Laurie H
authors.initials: LH
authors.lastname: Glimcher
mesh_terms: D000022:Abortion, Spontaneous / Q000276:immunology*; D000818:Animals; D019013:CD40 Antigens / Q000276:immunology; D003338:Corpus Luteum / Q000276:immunology / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D005313:Fetal Death; D007249:Inflammation; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D011247:Pregnancy; D016649:Primary Ovarian Insufficiency / Q000276:immunology*; D011981:Receptors, Prolactin / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
chemical_list: D019013:CD40 Antigens; D011981:Receptors, Prolactin; D014409:Tumor Necrosis Factor-alpha