PREOVULATORY ADMINISTRATION OF CLOMIPHENE CITRATE TO MICE CAUSES FETAL GROWTH-RETARDATION AND NEURAL-TUBE DEFECTS (EXENCEPHALY) BY AN INDIRECT MATERNAL EFFECT
PREOVULATORY ADMINISTRATION OF CLOMIPHENE CITRATE TO MICE CAUSES FETAL GROWTH-RETARDATION AND NEURAL-TUBE DEFECTS (EXENCEPHALY) BY AN INDIRECT MATERNAL EFFECT
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DOI：
10.1002/tera.1420470403
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发表时间：
1993-04-01
期刊：
影响因子：
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通讯作者：
DZIADEK, M
中科院分区：
文献类型：
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作者：
DZIADEK, M
在排卵前、排卵后着床前期和着床后，以不同剂量和不同时间给予雌性小鼠克罗米芬。在妊娠第15天确定妊娠结局，计算相对于排卵数的流产和吸收数，并评估胎仔的大小和发育阶段以及形态异常。排卵前给予克罗米芬可导致着床率降低和存活胎儿生长迟缓，其影响程度取决于药物注射的剂量和时间。在排卵前立即给予克罗米酚，着床率最低，胎儿生长迟缓程度最高。在排卵前注射克罗米酚的雌性动物的胎儿中发现露脑畸形的发生率增加。将处理过的小鼠的胚泡转移到未处理过的培养物中，表明克罗米芬对着床和胎儿生长的影响主要是通过雌性生殖道介导的，而不是对胚胎本身的直接影响。在着床前给予克罗米芬可完全抑制着床，而在着床后给予克罗米芬的唯一效果是胎儿体重轻微减轻。这些结果表明，排卵前克罗米酚柠檬酸盐损害子宫功能，这对着床后胚胎的生长和发育有间接影响。
Clomiphene citrate was administered to female mice at different doses and different times prior to ovulation, in the preimplantation period after ovulation, and after implantation. Pregnancy outcome was determined on day 15 of gestation, when the number of implantations and resorptions were calculated relative to the number of ovulations, and fetuses were assessed for size and stage of development and morphological abnormalities. Preovulatory administration of clomiphene citrate caused decreased implantation rates and growth retardation of surviving fetuses, the degree of the effect being dependent on the dose and the time of drug injection relative to ovulation. The implantation rate was lowest, and the degree of fetal growth retardation highest, when clomiphene citrate was administered immediately before ovulation. An increased incidence of exencephaly was found in the fetuses of females injected with clomiphene citrate prior to ovulation. Transfer of blastocysts from treated mice to untreated fosters showed the effect of clomiphene citrate on implantation and fetal growth to be predominantly mediated through the female reproductive tract, rather than a direct effect on the embryo itself. Administration of clomiphene citrate in the preimplantational period resulted in complete inhibition of implantation, while the only effect when administration was after implantation was a slight reduction in fetal weight. These results indicate that preovulatory clomiphene citrate impairs uterine function, which has an indirect effect on the growth and development of the postimplantation embryo.