Taguchi O, Nishizuka Y, Sakakura T, Kojima A
Clin Exp Immunol. 1980 Jun;40(3):540-53.
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.
我们实验室之前的研究描述了一种特殊类型的卵巢发育不全，它在出生后2 - 4天的关键时期对新生小鼠进行胸腺切除术后出现。本实验提供的证据有力地表明了这一现象的自身免疫病因。通过间接免疫荧光（IFL）和辣根过氧化物酶（HRPO）标记抗体技术，证明了新生期胸腺切除的（C57B1/6Cr×A/JCr）F1（B6A）和（C3H/HeMs×129/J）F1（C31）杂种小鼠产生针对生长卵泡中卵母细胞卵质的循环自身抗体（AOA），但不针对原始卵泡中的卵母细胞。AOA的出现与卵巢炎的发展密切相关，卵巢炎的特征是成年早期卵母细胞迅速且完全丧失。在B6A和C31小鼠中，出生后第3天进行胸腺切除（Tx - 3）后出现卵巢炎且血清中出现AOA，但出生后第0天或第7天进行胸腺切除后则未出现。此外，在无胸腺的B6A和C31裸鼠中，既未检测到卵巢炎也未检测到AOA。用同基因正常成年卵巢匀浆能完全吸收AOA，但用X射线照射的无卵卵巢或颗粒细胞瘤匀浆则不能，这可能表明AOA具有特异性。在胸腺切除小鼠的血清中，首次在第30 - 40天检测到AOA，此时其卵巢显示卵泡退化明显增强，许多卵母细胞死亡，伴有或不伴有淋巴细胞浸润。在第50 - 90天，通过IFL技术检测到血清中AOA的高滴度，可检测到稀释倍数超过2000倍的AOA；然而，AOA的滴度随年龄逐渐降低，在第150 - 360天消失，此时萎缩的卵巢中已无卵母细胞。出生后第3天进行胸腺切除的小鼠偶尔会产生针对透明带的自身抗体，针对卵巢类固醇生成细胞的自身抗体产生频率较低。这些数据表明，在小鼠出生后不久的关键时期进行胸腺切除会导致自身免疫性卵巢炎，随后导致早期不育。
