Autoimmune oophoritis in thymectomized mice: detection of circulating antibodies against oocytes

Previous studies from our laboratory described a particular type of ovarian dysgenesis which develops in mice after neonatal thymectomy (Tx) at the critical age of 2-4 days after birth. The present experiment provides evidence which strongly suggests an autoimmune aetiology for this phenomenon. By indirect immunofluorescence (IFL) and horse-radish peroxidase (HRPO) labelled antibody techniques, it was demonstrated that neonatally Tx mice of (C57B1/6Cr x A/JCr)F1 (B6A) and (C3H/HeMs x 129/J)F1 (C31) hybrids produce circulating autoantibody(ies) against ooplasma of oocytes (AOA) in growing follicles, but not against oocytes in primordial follicles. Appearance of AOA was closely correlated with the development of oophoritis which ws characterized by a rapid and complete loss of oocytes at early adulthood. In B6A and C31 mice, oophoritis occurred and AOA appeared in sera after Tx at day 3(Tx -- 3) but not after Tx at days 0 or 7. Also, in athymic B6A and C31 nude mice neither oophoritis or AOA were detectable. Complete absorption of AOA with homogenates of isogeneic normal adult ovaries, but not with homogenates of X-ray-irradiated anovular ovaries or granulosa cell tumour may indicate the specificity of AOA. AOA was first demonstrated at day 30-40 in sera of Tx mice, whose ovaries showed a marked enhancement of follicular degeneration and the death of numerous occytes with or without lymphocyte infiltration. High titres of AOA, detectable in sera of more than 2,000-fold dilutions, were assayed by the IFL technique at day 50-90; however, AOA gradually diminished in titre with age and disappeared at day 150-360 when no oocytes remained in the atrophic ovary. Mice thymectomized at day 3 occasionally produced autoantibodies against zona pellucida and with lesser frequency against steroid-producing cells of the ovary. These data indicate that in the mouse Tx at the critical age shortly after birth produces autoimmune oophoritis, subsequently resulting in early sterility.