Disruption of estrous cycle homeostasis in mice with experimental autoimmune encephalomyelitis

• We examined changes in the estrous cycle in EAE mice.
• We found that EAE mice have significantly shorter estrous cycles.
• Rapid estrous cycling in EAE is due to shorter luteal and longer follicular phases.
• CNS autoimmunity can cause the uterine cycle abnormalities often observed in MS.

Multiple sclerosis (MS) is widely viewed as a prototypic human autoimmune disease involving proinflammatory T cells that induce lesions in the central nervous system (CNS) in response to myelin self proteins. Although the impact of sex hormones on MS is well recognized, the converse effects of autoimmunity on sex hormones are still unclear. The current study was designed to assess the impact of CNS autoimmunity on female reproductive physiology. In order to identify subtle hormonal disturbances as a result of autoimmunity, we analyzed the estrous cycle in SJL/J mice after active induction of experimental autoimmune encephalomyelitis (EAE), an animal model with substantial similarities to MS. Here we show that CNS autoimmunity significantly shortens the murine estrous cycle. This shortening of the estrous cycle is characterized by a dramatic decrease in the length of the metestrus–diestrus luteal phase partially offset by a highly significant but less dramatic elongation of the proestrus–estrus follicular phase of the uterine cycle. Thus, our study provides experimental evidence for a direct causal link between CNS autoimmunity and disruption of the homeostatic balance of the uterine cycle often observed in women with MS.