Stress‐Triggered Abortion in Mice Prevented by Alloimmunization

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Abstract
To determine if immunotherapy can prevent abortion triggered by mechanisms that in humans may be treatable by psychotherapy. The effects of alloimmunization against paternal strain antigens were tested in pregnant mice subjected to stress. Restraint stress boosted the resorption rate assessed on day 13.5 of pregnancy in DBA/2-mated C3H/HeJ mice with an optimal effect on day 4.5 of pregnancy, and premating alloimmunization greatly reduced the effect. By contrast, CBA/J and A/J mice proved resistant to abortion boosting by restraint stress. A/J mice mated to DBA/2 or C3H/HeJ males showed reduced fertility, perhaps due to failure of pregnancy immediately after the stress, but this was not corrected by alloimmunization with either DBA/2 [class I + class II major histocompatibility complex (MHC) immunogen] or C3H/HeJ (class I MHC immunogen) splenocytes. There was a reduction in the endogenous resorption rate, however, and implantation number was slightly increased by preimmunization using DBA/2 cells. The abortion rate could be boosted, however, by ultrasonic noise stress of high abortion rate CBA/J, and preimmunization using BALB/c (H-2d) splenocytes protected. A similar boosting of loss in low abortion rate BALB/k mice was ameliorated (albeit not completely) by preimmunization with allogenic paternal but not syngeneic splenocytes. Immunotherapy may protect against a variety of potential triggers of spontaneous abortion, including those that may be amenable to psychological remedies, and possible mechanisms are discussed.