Center for Reproductive Sciences, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Reprod Toxicol. 2011 Nov;32(3):286-92. doi: 10.1016/j.reprotox.2011.07.005. Epub 2011 Jul 30.
Aryl hydrocarbon receptor (AHR) ligands, including 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD), accelerate reproductive senescence and one proposed target is the early embryo. To discriminate between direct effects on the oocyte and early embryo and those mediated by complex ovarian interactions with TCDD, IVF was carried out in the presence of TCDD (10, 100 nM) and the aryl hydrocarbon antagonist CH-223191 (1 μM) combined factorially. TCDD-induced Cyp1a1 mRNA expression was absent in 2-cell embryos; however morulae exhibit dose-dependent Cyp1a1 expression. TCDD induced accumulation of sperm in the perivitelline space and displacement of blastomere nuclei. At 100 nM TCDD, aberrations in cytokinesis and nuclear positioning were observed 2-cell embryos and morula and these effects were reversed in the presence of CH-223191. Our data suggest that acute exposure to TCDD has direct effects on early development in the rat that permit discrimination of AHR-mediated and AHR-independent mechanisms through which environmental toxicants impair mammalian reproduction.
芳烃受体 (AHR) 配体，包括 2,3,7,8-四氯二苯并对二恶英 (TCDD)，加速生殖衰老，一个被提议的靶标是早期胚胎。为了区分 TCDD 对卵母细胞和早期胚胎的直接影响与 TCDD 通过与卵巢的复杂相互作用介导的影响，在存在 TCDD（10、100 nM）和芳基烃拮抗剂 CH-223191（1 μM）的情况下进行了体外受精（IVF），并进行了组合因子分析。TCDD 在 2 细胞胚胎中诱导 Cyp1a1 mRNA 表达缺失；然而，桑椹胚表现出 Cyp1a1 表达的剂量依赖性。TCDD 诱导精子在卵周隙中的积累，并使卵裂球核移位。在 100 nM TCDD 下，2 细胞胚胎和桑椹胚中观察到胞质分裂和核定位的异常，并且在存在 CH-223191 的情况下，这些作用得到逆转。我们的数据表明，急性暴露于 TCDD 对大鼠的早期发育有直接影响，这使得可以通过区分 AHR 介导和 AHR 不依赖的机制来区分环境毒物损害哺乳动物生殖的机制。
