小鼠胚胎植入前暴露甲氧滴滴涕和雌二醇影响出生后发育

Preimplantation exposures of murine embryos to methoxychlor or estradiol affect postnatal development

目的研究在小鼠妊娠早期（前植入）体内暴露雌激素样甲氧滴滴涕（MXC）或雌二醇的长期效应。方法妊娠1—3天孕鼠给予皮下注射1μg的雌二醇和5．0mg的MXC（出现阴道栓为第0天）。妊娠对照组小鼠仅用载体芝麻油处理。检测胎仔数，出生后的生存率，出生时的性别比率和两种性别子代的肛门与生殖器间距离（AGD），同时检测雌性子代阴道开放时间。采用放射免疫法检测雄性子代血清黄体生成素（LH）、卵泡刺激素（FSH）和睾丸酮（T）含量。结果由于MXC暴露的子代可记录高的死亡率。暴露雌二醇或MXC不能改变出生时的性别比率，但是胎仔数减少。出生后21天雄性仔鼠AGD比对照组短，此变化在MXC处理组最为明显。在MXC暴露后雌性子代的AGD没有受到影响，但是雌二醇处理组雌性小鼠的AGD比对照组更长。植入前暴露雌二醇或MXC使更多的雌性小鼠在断奶时明显出现早熟阴道开放。MXC处理组的雄性小鼠可降低血LH和FSH但是不改变睾丸酮水平。结论在前植入阶段暴露MXC或雌二醇造成在两性子代断乳后长期的性发育改变。MXC处理也阻滞两性子代的发育和体重。

Objective To study the long-term effects of in vivo exposures to proestrogen meth- oxychlor （MXC） or estradiol during early pregnancy （preimplantation） in mice. Methods Pregnant dams received either subcutaneous injections of 1 g of estradiol （ E2 ） and 5.0 mg of MXC on Days 1 3 of pregnancy （ vaginal plug = Day 0）. Pregnant control mice were treated with the vehicle only. Litter size, postnatal survival, sex ratio at birth, and anogenital distance （AGD） in offspring of both sexes were examined, as well as vaginal opening in female off- spring. The concentrations of LH, FSH and testosterone （T） in sera of the pregnant mice were determined using radioimmunoassay. Results High mortality rate was recorded in MXC-exposed offspring due to infanticide. Exposures to either E2 or MXC did not change sex ratio at birth, but the litter size was smaller in the former group. On postnatal Day 21, male pups ex- posed to either E2 or MXC at preimplantation stage exhibited shorter AGD than the controls, with the change most pronounced after MXC treatments. AGD in female offspring was unaffect- ed after MXC exposures, but E2 treatments produced longer AGD in the females than that recor- ded in the controls. Preimplantation exposures to E2 or MXC also accelerated sexual maturation as significantly more females exhibited precocious vaginal opening at weaning. In males, MXC exposure during early pregnancy decreased serum LH and FSH, but not testosterone levels. Conclusion Exposures to MXC or E2 at preimplantation stages cause long term alteration of sexual development during weaning in offspring of both sexes. Also, MXC treatments retarded both growth and weight of both sexes of offspring.