Laskey J W, Berman E
Reproductive Toxicology Branch, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina.
Reprod Toxicol. 1993;7(1):25-33. doi: 10.1016/0890-6238(93)90006-s.
In vitro ovary culture in rats was used to characterize ovarian steroidogenesis and to evaluate changes produced by in vivo exposure to bis(2-diethylhexyl)phthalate (DEHP). Steroid profiles [progesterone (P4), estradiol (E2), and testosterone (T)] from cultures of minced ovary were obtained in untreated immature and mature rats, and from mature rats treated with DEHP. A 1-h incubation without human chorionic gonadotropin (hCG) was used to produce an initial steroidogenic profile. Three 1-h incubations with hCG were used to produce a stimulated steroid profile. A combination of initial and stimulated ovarian steroid profiles was shown to correctly identify the stage of the cycle in all untreated rats, using multivariate statistical analysis. Separately, initial or stimulated ovarian steroid profiles correctly identified the stage of the cycle in more than 90% of the rats. The statistical analysis using a combination of variables (multivariate) indicated that DEHP-treated rats were significantly different (P < 0.001) from sham-treated rats. In fact, the alteration caused by DEHP in the in vitro ovarian steroidogenic profile was most apparent in rats during diestrus and estrus. In DEHP-treated rats in diestrus, ovarian steroidogenesis appeared to shift to the production of more T and more E2 than in untreated rats in diestrus. The change seen in steroid profiles in DEHP-treated rats in estrus is to decreased E2 production. The steroid profile from ovary culture in conjunction with vaginal cytology was very useful in correctly identifying in vivo DEHP-treated rats, and will be a useful in vitro technique in the evaluation of ovarian toxicants in cycling females.
采用大鼠体外卵巢培养来表征卵巢类固醇生成，并评估体内暴露于双（2-二乙基己基）邻苯二甲酸酯（DEHP）所产生的变化。在未处理的未成熟和成熟大鼠以及经DEHP处理的成熟大鼠中，获取切碎卵巢培养物中的类固醇谱[孕酮（P4）、雌二醇（E2）和睾酮（T）]。使用无人类绒毛膜促性腺激素（hCG）的1小时孵育来产生初始类固醇生成谱。使用hCG进行三次1小时孵育以产生刺激后的类固醇谱。使用多变量统计分析表明，初始和刺激后的卵巢类固醇谱组合能够正确识别所有未处理大鼠的发情周期阶段。单独来看，初始或刺激后的卵巢类固醇谱能在超过90%的大鼠中正确识别发情周期阶段。使用变量组合（多变量）的统计分析表明，DEHP处理的大鼠与假处理的大鼠有显著差异（P < 0.001）。事实上，DEHP对体外卵巢类固醇生成谱的改变在间情期和发情期的大鼠中最为明显。在间情期经DEHP处理的大鼠中，卵巢类固醇生成似乎转向产生比未处理的间情期大鼠更多的T和更多的E2。在发情期经DEHP处理的大鼠中，类固醇谱的变化是E2产生减少。卵巢培养的类固醇谱与阴道细胞学相结合，在正确识别体内经DEHP处理的大鼠方面非常有用，并且将成为评估周期性雌性动物卵巢毒物的一种有用的体外技术。
