title: The aryl hydrocarbon receptor agonist 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) alters early embryonic development in a rat IVF exposure model.
abstract: 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.
authors.affiliation: Center for Reproductive Sciences, University of Kansas Medical Center, Kansas City, KS 66160, USA. bpetroff@kumc.edu
authors.forename: Brian K
authors.initials: BK
authors.lastname: Petroff
authors.forename: Kelli E
authors.initials: KE
authors.lastname: Valdez
authors.forename: Sara B
authors.initials: SB
authors.lastname: Brown
authors.forename: Joanna
authors.initials: J
authors.lastname: Piasecka
authors.forename: David F
authors.initials: DF
authors.lastname: Albertini
mesh_terms: D000818:Animals; D001391:Azo Compounds / Q000494:pharmacology; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D047108:Embryonic Development / Q000187:drug effects*; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D005307:Fertilization in Vitro; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D008297:Male; D023421:Models, Animal; D009028:Morula / Q000187:drug effects / Q000201:enzymology; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011247:Pregnancy; D011720:Pyrazoles / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists* / Q000037:antagonists & inhibitors; D013084:Sperm-Ovum Interactions / Q000187:drug effects; D013723:Teratogens / Q000633:toxicity*
chemical_list: C511621:2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide; D001391:Azo Compounds; D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D011720:Pyrazoles; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D013723:Teratogens; D019363:Cytochrome P-450 CYP1A1