Collagen‐Induced Arthritis and Pregnancy in Mice: The Effects of Pregnancy on Collagen‐Induced Arthritis and the High Incidence of Infertility in Arthritic Female Mice

ABSTRACT: Collagen‐induced arthritis (CIA) in mice is a model of inflammatory polyarthritis that has many features similar to human rheumatoid arthritis. In rheumatoid arthritis, pregnancy leads to amelioration of the disease while exacerbation develops after delivery. We used the CIA model to elucidate the role of pregnancy on disease and vice versa. The onset of arthritis in pregnant mice was delayed in the B10.RIII strains immunized with native porcine type II collagen 7–12 days prior to syngeneic [B10.RIII (susceptible to CIA) × B10.RIII] and allogeneic (B10.RIII female × B10.K male that are CIA resistant) pregnancy. In contrast, when mice were immunized on days 1–6 of pregnancy, the onset of arthritis was earlier as compared with controls. In addition, once the mice developed CIA after delivery, the disease showed markedly rapid progression as compared to the control immunized group. Humoral immune responses to type II collagen showed significantly decreased levels on day 14 (at late stage of pregnancy) both in syngeneic and allogeneic postmating immunized pregnant mice. The same effect was also seen in allogeneic premating immunized pregnant mice on day 21 (at mid‐stage of pregnancy). The levels of these antibodies increased after delivery. Subclasses of IgG₁ and IgG_2a antibodies to type II collagen were suppressed during pregnancy. In the pseudopregnant group, these antibodies showed decreased levels on day 14, but did not differ from the control groups on day 21 and 28. Some immunoregulatory changes may play a role in these alterations in pregnant arthritic mice. In comparison to the effects of syngeneic (susceptible × susceptible) pregnancy on CIA, allogeneic (susceptible female × resistant male) pregnancy seemed to be beneficial for the affected individuals. Litter size and mean birth weight were not affected by immunization of type II collagen. After onset of CIA, both syngeneic and allogeneic matings failed to produce offspring in arthritic female mice. The estrus cyclicity was highly disturbed in arthritic female mice and gonadotropin stimulation in arthritic mice induced significantly less ova in oviducts and maturing follicles as compared to nonarthritic controls. Immunological factors yet to be elucidated may be involved in this ovarian dysfunction. 1986 Munksgaard