On use of animal models

Emerging Topics in Life Sciences
David A Clark

Abstract

Human pregnancy, critical for our species survival, is inefficient and prone to complications such as infertility, spontaneous miscarriages and preeclampsia (PE). Immunological factors may be important as the embryo is 50% paternal and foreign to the mother. Mouse pregnancy models, and in particular the murine CBA/J x DBA/2 mating combination, has been widely used to investigate mechanisms causing and preventing partner-specific recurrent miscarriages (RM) and PE. Occult losses can represent T cell-mediated rejection, and antigen-specific regulatory T cells (Tregs) with classical αβ T cell receptors (TcR) activated by semen antigens at the time of mating are protective. If there is no occult loss, an inadequate Treg response can also predispose to RM. In RM, proinflammatory cytokines from natural killer (NK)-type cells and macrophages of the innate immune system are responsible and cells with γδ TcR protect via release of TGF-β-type molecules. Immunization of abortion-prone female CBA/J mice or administration of cell-associated or soluble CD200, an immune check point inhibitor, can prevent abortions by augmenting uterine decidual suppressor cell activity. Human studies suggest that is also true in couples with RM. Environmental...Continue Reading

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