Ovarian insufficiency and early pregnancy loss induced by activation of the innate immune system
Adrian Erlebacher, … , Albert F. Parlow, Laurie H. Glimcher
Adrian Erlebacher, … , Albert F. Parlow, Laurie H. Glimcher
Published July 1, 2004
Citation Information: J Clin Invest. 2004;114(1):39-48. https://doi.org/10.1172/JCI20645.
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Article Immunology

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-α 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

Adrian Erlebacher, Dorothy Zhang, Albert F. Parlow, Laurie H. Glimcher

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Involvement of TNF-α in anti-CD40–induced pregnancy failure. (A) Elevate...
Involvement of TNF-α in anti-CD40–induced pregnancy failure. (A) Elevated TNF-α and IL-6 serum concentrations 24 hours after treatment with anti-CD40 antibodies (FGK45). Data represent mean ± SEM of five mice per group. The limits of detection were 31.1 pg/ml TNF-α and 54.7 pg/ml IL-6. ND, not detectable. (B and C) NF-κB p65 distribution in E4 corpora lutea visualized by immunostaining. Whereas the p65 distribution was cytoplasmic in mice treated 24 hours earlier on E4 with control rat IgG (B), it assumed a nuclear distribution when mice were treated with FGK45 (C). Data represent immunostained ovaries from three mice per group. Scale bar: 50 μm.