[Analysis of experimental autoimmune oophoritis as a model of premature ovarian failure]

Neonatal thymectomy in mice at 3 days of age (Tx-3) can induce autoimmune oophoritis and results in complete loss of oocyte at young adult age. We examined endocrinological and immunological abnormalities in Tx-3 (C3H/He X A/J)F1 female mice to find some similarities to premature ovarian failure (POF) in humans. The majority of the Tx-3 mice showed irregular estrous cycles during 7 to 9 weeks of age then fell into continuous diestrous. Endocrinological analysis of Tx and sham-Tx mice revealed that serum gonadotropin levels (LH and FSH) of Tx-3 mice rapidly increased from 8 weeks of age and serum estradiol levels significantly decreased from 10 weeks of age (P less than 0.05). In contrast with estradiol, serum androstenedione levels significantly increased from 10 weeks of age (P less than 0.01). In the mice with oophoritis, circulating autoantibodies against ooplasm and/or zona pellucida determined by immunoperoxidase method could be detected from 6 weeks of age, became high titer from one or two weeks later, but resulted in low titer or negative test from about 4 months of age. Acute loss of oocyte with massive mononuclear cell infiltration coincident with the appearance of these autoantibodies were progressed, and then atrophic ovaries with complete destruction of follicles were seen at 3 months of age. This experimental model of autoimmune oophoritis abounds in suggestion for the understanding of one of the possible etiology of POF in women.