Women's Reproductive Health Research Center, Department of Obstetrics & Gynecology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Reprod Toxicol. 2011 Apr;31(3):344-50. doi: 10.1016/j.reprotox.2010.10.003. Epub 2010 Oct 16.
TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) is a ubiquitous environmental contaminant and known endocrine disruptor. Since humans and animals are most sensitive to toxicant exposure during development, we previously developed a mouse model of in utero TCDD exposure in order to examine the impact of this toxicant on adult reproductive function. Our initial in utero toxicant-exposure study revealed a dose-dependent reduction in uterine sensitivity to progesterone; however, we did not previously explore establishment or maintenance of pregnancy. Thus, in the current study, we examined pregnancy outcomes in adult C57BL/6 mice with a history of developmental TCDD exposure. Herein we demonstrate reduced fertility and an increased incidence of premature birth (PTB) in F1 mice exposed in utero to TCDD as well as in three subsequent generations. Finally, our studies revealed that mice with a history of developmental TCDD exposure exhibit an increased sensitivity to inflammation which further negatively impacted gestation length in all generations examined.
TCDD（2,3,7,8-四氯二苯并对二恶英）是一种普遍存在的环境污染物，也是一种已知的内分泌干扰物。由于人类和动物在发育过程中对毒物暴露最为敏感，我们之前开发了一种在子宫内暴露于 TCDD 的小鼠模型，以研究这种毒物对成年生殖功能的影响。我们之前的宫内毒物暴露研究表明，子宫对孕激素的敏感性呈剂量依赖性降低；然而，我们之前并未探讨妊娠的建立或维持。因此，在目前的研究中，我们研究了具有 TCDD 发育暴露史的成年 C57BL/6 小鼠的妊娠结局。在此，我们证明了在子宫内暴露于 TCDD 的 F1 小鼠以及随后的三代小鼠中，生育力降低和早产（PTB）的发生率增加。最后，我们的研究表明，具有 TCDD 发育暴露史的小鼠对炎症的敏感性增加，这进一步对所有研究的妊娠时间产生负面影响。
