Female mice deficient in steroid 5alpha-reductase type 1 have a decreased litter size. The average litter in homozygous deficient females is 2.7 pups vs. 8.0 pups in wild type controls. Oogenesis, fertilization, implantation, and placental morphology appear normal in the mutant animals. Fetal loss occurs between gestation days 10.75 and 11.0 commensurate with a midpregnancy surge in placental androgen production and an induction of 5alpha-reductase type 1 expression in the decidua of wild type mice. Plasma levels of androstenedione and testosterone are 2- to 3-fold higher on gestation day 9, and estradiol levels are chronically elevated by 2- to 3-fold throughout early and midgestation in the knockout mice. Administration of an estrogen receptor antagonist or inhibitors of aromatase reverse the high rate of fetal death in the mutant mice, and estradiol treatment of wild type pregnant mice causes fetal wastage. The results suggest that in the deficient mice, a failure to 5alpha-reduce androgens leads to their conversion to estrogens, which in turn causes fetal death in midgestation. These findings indicate that the 5alpha-reduction of androgens in female animals plays a crucial role in guarding against estrogen toxicity during pregnancy.

译文

:缺乏1型甾体5α-还原酶的雌性小鼠的窝产仔数减少。纯合缺陷型雌性的平均产仔数为2.7头,而野生型对照为8.0头。在突变动物中,卵子发生,受精,着床和胎盘形态正常。胎儿丢失发生在妊娠10.75至11.0天之间,与胎盘雄激素产生的中期妊娠激增和野生型小鼠蜕膜中5α-还原酶1型表达的诱导相称。在敲除第9天,雄烯二酮和睾丸激素的血浆水平要高2至3倍,而雌二醇水平在整个妊娠早期和中期都长期升高2至3倍。在突变小鼠中施用雌激素受体拮抗剂或芳香酶抑制剂可逆转高死亡率的胎儿死亡,而雌二醇治疗野生型妊娠小鼠会造成胎儿浪费。结果表明,在有缺陷的小鼠中,未能通过5α-还原雄激素导致其转化为雌激素,进而导致妊娠中期胎儿死亡。这些发现表明,雌性动物体内雄激素的5α-还原在预防妊娠期雌激素毒性中起着至关重要的作用。

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