Miyake T, Sato Y, Takeuchi S, Taguchi O
Department of Obstetrics and Gynecology, Niigata School of Medicine.
Nihon Naibunpi Gakkai Zasshi. 1988 Aug 20;64(8):645-54. doi: 10.1507/endocrine1927.64.8_645.
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.
在3日龄时对小鼠进行新生期胸腺切除术(Tx-3)可诱发自身免疫性卵巢炎,并导致成年早期卵母细胞完全丧失。我们研究了Tx-3(C3H/He×A/J)F1雌性小鼠的内分泌和免疫异常情况,以寻找与人类卵巢早衰(POF)的一些相似之处。大多数Tx-3小鼠在7至9周龄时出现不规则发情周期,随后进入持续间情期。对Tx小鼠和假手术Tx小鼠的内分泌分析显示,Tx-3小鼠的血清促性腺激素水平(LH和FSH)从8周龄开始迅速升高,血清雌二醇水平从10周龄开始显著下降(P<0.05)。与雌二醇相反,血清雄烯二酮水平从10周龄开始显著升高(P<0.01)。在患有卵巢炎的小鼠中,通过免疫过氧化物酶法测定的针对卵质和/或透明带的循环自身抗体从6周龄开始即可检测到,1至2周后滴度升高,但在约4月龄时滴度降低或检测为阴性。随着这些自身抗体的出现,伴有大量单核细胞浸润的卵母细胞急性丧失不断进展,然后在3月龄时可见卵泡完全破坏的萎缩卵巢。这种自身免疫性卵巢炎的实验模型为理解女性POF的可能病因之一提供了丰富的线索。