Johnson D C, Sen M, Kogo H, Dey S K
Department of Gynecology and Obstetrics, Ralph L. Smith Research Center, University of Kansas Medical Center, Kansas City 66103.
Proc Soc Exp Biol Med. 1990 Oct;195(1):44-50. doi: 10.3181/00379727-195-43116.
The effect of chlordecone (Kepone), an insecticide/fungicide with reproductive toxicity, on the early stages of pregnancy in the rat was studied. Intraperitoneal injection of chlordecone into adult virgin female Holtzman strain rats before mating, in doses as high as 80 mg/kg, did not prevent fertilization, early development of the embryo to the blastocyst stage, transport of the embryo through the oviduct, or its implantation into the uterus. However, a single dose of 60 or 80 mg/kg, but not 20 or 40 mg/kg, before mating significantly reduced the concentration of progesterone in the serum of rats undergoing normal embryo implantation 5 days later. A dose of 80 mg/kg of chlordecone reduced progesterone levels in the serum by more than 50% within 48 hr in ovariectomized rats with Silastic tubing implants containing crystalline progesterone. This dose of chlordecone induced deciduomata formation in progesterone-primed ovariectomized rats to the same extent as 1 microgram of estradiol benzoate. The minimal effective single dose of chlordecone to initiate implantation of blastocysts in the uteri of hypophysectomized progesterone-primed rats, and to maintain embryo development for at least 5 days, was 50 mg/kg. Daily doses of 20 mg/kg for 3 or 5 days were effective at initiating implantation but did not maintain pregnancy. The latter treatment, however, did not prevent initiation of implantation or embryo development induced by subsequent administration of estrone. The results are consistent with the view that chlordecone is a weak estrogen that has both nongenomic and genomic estrogenic actions.
研究了具有生殖毒性的杀虫剂/杀菌剂十氯酮（开蓬）对大鼠妊娠早期的影响。在成年未交配的雌性霍尔茨曼品系大鼠交配前腹腔注射高达80mg/kg剂量的十氯酮，并未阻止受精、胚胎早期发育至囊胚阶段、胚胎通过输卵管的运输或其植入子宫。然而，在交配前单次注射60或80mg/kg（而非20或40mg/kg）的十氯酮，可显著降低5天后正常胚胎植入的大鼠血清中孕酮的浓度。在植入含有结晶孕酮的硅橡胶管的去卵巢大鼠中，80mg/kg剂量的十氯酮在48小时内使血清中孕酮水平降低超过50%。该剂量的十氯酮在孕酮预处理的去卵巢大鼠中诱导蜕膜形成的程度与1微克苯甲酸雌二醇相同。在垂体切除、孕酮预处理的大鼠子宫中启动囊胚植入并维持胚胎发育至少5天的十氯酮最小有效单剂量为50mg/kg。连续3天或5天每日注射20mg/kg可有效启动植入，但不能维持妊娠。然而，后一种处理并未阻止随后给予雌酮诱导的植入启动或胚胎发育。这些结果与十氯酮是一种具有非基因组和基因组雌激素作用的弱雌激素这一观点一致。
