MULLERIAN REMNANTS OF MALE-MICE EXPOSED PRENATALLY TO DIETHYLSTILBESTROL
MULLERIAN REMNANTS OF MALE-MICE EXPOSED PRENATALLY TO DIETHYLSTILBESTROL
复制标题
DOI：
10.1002/tcm.1770070405
复制
发表时间：
1987-01-01
期刊：
影响因子：
--
通讯作者：
MCLACHLAN, JA
中科院分区：
文献类型：
--
作者：
NEWBOLD, RR;BULLOCK, BC;MCLACHLAN, JA
男性产前暴露于己烯雌酚（DES）会导致生殖道畸形，即苗勒管残留。尚未研究这些残留物发生病理变化的可能性。因此，在妊娠第9天至第16天，向妊娠远系杂交CD-1小鼠皮下注射每日剂量的DES（100 μ g/kg）。在10至18月龄时处死DES暴露的雄性后代和年龄匹配的对照雄性小鼠，并检查生殖道异常。在277只DES暴露雄性小鼠中的268只（97%）中观察到显著的苗勒管残留。这些残余物分化为与输卵管和子宫同源的“雌性样结构”。苗勒管残端常呈囊状增大，并与邻近的男性结构共享支持结缔组织。以前报告的病变，称为“附睾囊肿”，经组织学确定为囊性“输卵管样”结构，因此，被认为是苗勒管异常。这些雄性输卵管和子宫同源物的病理变化包括良性和恶性病变。此外，附睾结构也发生了改变。炎症和精子肉芽肿在DES治疗的小鼠中普遍存在，年龄小至10月龄，但仅在对照小鼠中观察到18个月。还观察到附睾管起源囊肿、增生和附睾管腺瘤。在122只相应年龄的对照雄性动物中未观察到可比异常。本报告中提供的数据表明，经胎盘暴露于DES会影响男性生殖道的分化和正常发育，包括苗勒管（副中肾）和沃尔夫管（中肾）。这些组织的长期变化包括病变，其中一些类似于瘤形成，尽管病变的自然史尚不清楚。此外，一些先前描述的称为“附睾囊肿”的异常与来自胚胎女性起源的组织有关。
Prenatal exposure of males to diethylstilbestrol (DES) results in reproductive tract teratogenesis, ie, retention of Mullerian duct remnants. The potential of these remnants to develop pathological changes has not been studied. Therefore, pregnant outbred CD-1 mice were subcutaneously injected with daily doses of DES (100 .mu.g/kg) on days 9 through 16 of gestation. DES-exposed male offspring and age-matched control male mice were sacrificed at 10 to 18 mo of age and examined for reproductive tract abnormalities. Prominent Mullerian remnants were observed in 268 out of 277 (97%) of the DES-exposed male mice. These remnants differentiated into "femalelike structures" homologous to oviduct and uterus. The Mullerian remnants were often enlarged and cystic and shared supporting connective tissue with adjacent male structures. Previously reported lesion, termed "epididymal cysts," were determined histologically to be cystic "oviductlike" structures and were, therefore, considered a Mullerian duct abnormality. Pathological changes in these male oviductal and uterine homologs included benign and malignant lesions. In addition, epididymal structures were altered. Inflammation and sperm granulomas were prevalent in DES-treated mice as young as 10 mo old but were only observed in control mice at 18 mos. Cysts of epididymal duct origin, hyperplasia, and adenoma of the epididymal duct were also observed. No comparable abnormalities were noted in 122 control males of corresponding ages. The data presented in this report demonstrated that transplacental exposure to DES affected the differentiation and normal development of the male genital tract involving both the Mullerian (paramesonephric) and Wolffian (mesonephric) ducts. The long-term changes in these tissues include lesion, some of which resembled neoplasia although the natural history of the lesions is not known. Moreover, some previously described abnormalities referred to as "epididymal cysts" were associated with tissues derived from embryonic female origin.