Iguchi T, Hirokawa M, Takasugi N
Toxicology. 1986 Dec 1;42(1):1-11. doi: 10.1016/0300-483x(86)90087-9.
Three groups of female C57BL/Tw mice given 5 daily injections of 2, 20 or 100 micrograms tamoxifen (Tx) starting on the day of birth were killed at 35 and 150 days of age. About a half of the mice killed at 150 days had been ovariectomized at 90 days. Uterine hypoplasia, myometrial involution and suppression of the uterine-gland genesis were found in the 2 age-groups of Tx-treated mice. Vaginal hypoplasia and hypospadia were common abnormalities in 150-day-old Tx-treated mice. Vaginal adenosis was encountered in 35-day-old mice treated neonatally with 20 or 100 micrograms Tx, but not in 150-day-old group. Permanent proliferation of vaginal epithelium was not induced by Tx. More than 80% of oocytes in small follicles were degenerated in Tx-exposed mice at 150 days, but not so in those at 35 days. Ovaries of neonatally Tx-exposed mice lacking corpora lutea made no luteinizing response to human chorionic gonadotropin injected prepubertally. Urinary-bladder hernia with or without caecum hernia frequently occurred in 150-day-old mice given 20 or 100 micrograms Tx. The present study revealed that neonatally administered Tx causes various abnormalities in gonad and genito-urinary tract of female C57BL/Tw mice.
从出生当天开始，对三组雌性C57BL/Tw小鼠每日注射5次，剂量分别为2微克、20微克或100微克他莫昔芬（Tx），在35日龄和150日龄时处死小鼠。在150日龄时处死的小鼠中，约一半在90日龄时已进行卵巢切除。在接受Tx治疗的两个年龄组的小鼠中，发现子宫发育不全、子宫肌层退化和子宫腺发生受抑制。阴道发育不全和尿道下裂是150日龄接受Tx治疗小鼠的常见异常。在出生时接受20微克或100微克Tx治疗的35日龄小鼠中发现阴道腺病，但在150日龄组中未发现。Tx未诱导阴道上皮的永久性增殖。在150日龄接受Tx处理的小鼠中，小卵泡中超过80%的卵母细胞发生退化，但在35日龄的小鼠中未出现这种情况。出生时接受Tx处理且缺乏黄体的小鼠卵巢，对青春期前注射的人绒毛膜促性腺激素无黄体化反应。在接受20微克或100微克Tx的150日龄小鼠中，经常出现伴有或不伴有盲肠疝的膀胱疝。本研究表明，出生时给予Tx会导致雌性C57BL/Tw小鼠的性腺和泌尿生殖道出现各种异常。
