Lenkowski JR et al. (2008), Perturbation of organogenesis by the herbicide ...

XB-ART-37316

Environ Health Perspect 2008 Feb 01;1162:223-30. doi: 10.1289/ehp.10742.

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Perturbation of organogenesis by the herbicide atrazine in the amphibian Xenopus laevis.

Lenkowski JR , Reed JM , Deininger L , McLaughlin KA .

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BACKGROUND: Exposure to anthropogenic chemicals during development can disrupt the morphogenesis of organ systems. Use of the herbicide atrazine has been debated in recent years because of its implicated, but poorly characterized, effects on vertebrates. Previous studies primarily examined the effects of atrazine exposure during metamorphosis or early developmental stages of amphibians. OBJECTIVES: We sought to identify and characterize the susceptibility during the often-overlooked developmental stage of organ morphogenesis. METHODS: We used a static renewal experimental treatment to investigate the effects of 10, 25, and 35 mg/L atrazine from early organ morphogenesis through the onset of tadpole feeding in the aquatic amphibian model system, Xenopus laevis. We quantified malformations of the body axis, heart, and intestine, as well as apoptosis in the midbrain and pronephric kidney. RESULTS: We found a significant dose-dependent increase in the percentage of atrazine-exposed tadpoles with malformations of multiple tissues including the main body axis, circulatory system, kidney, and digestive system. Incidence of apoptotic cells also increased in the both midbrain and kidney of atrazine-exposed tadpoles. CONCLUSIONS: Our results demonstrate that acute atrazine exposure (10-35 mg/L for < or = 48 hr) during early organ morphogenesis disrupts proper organ development in an amphibian model system. The concurrent atrazine-induced apoptosis in the pronephric kidney and midbrain begins to elucidate a mechanism by which atrazine may disrupt developmental processes in nontarget organisms.

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	Figure 1. Incidence of heart malformations. (A) Ventral views of normal NF stage 46 heart morphology (top) in an untreated-control tadpole, and hypertrophic (middle) and reduced (bottom) hearts in age-matched tadpoles exposed to 35 mg/L atrazine (DMSO) from NF stage 41–46. Hearts were visualized using the CT-3 antibody and are outlined in white. Bars = 0.2 mm. (B) Incidence of reduced and enlarged hearts in tadpoles exposed to 10, 25, or 35 mg/L atrazine or vehicle (DMSO) from NF stage 41, 42, or 43 through NF stage 46. Sample sizes are indicated above bars.**p < 0.001, and #p < 0.0001, as determined by post hoc pair-wise contrasts from logistic regression.
	Figure 2. Incidence of visceral hemorrhaging. (A) Lateral views, anterior facing right, of a control tadpole (top) and the visceral hemorrhaging phenotype observed near the opercular fold (arrowhead) and in the gut region (arrows) of a tadpole exposed to 35 mg/L atrazine (DMSO) (bottom) from NF stages 42–46. Bars = 0.5 mm. (B) Incidence of visceral hemorrhaging in tadpoles exposed to 10, 25, or 35 mg/L atrazine or vehicle (DMSO) from NF stage 41, 42, or 43 through NF stage 46. Sample sizes are indicated above bars.p < 0.05, *p < 0.001, and #p < 0.0001 as determined by post hoc pair-wise contrasts from logistic regression.
	Figure 3. Incidence of gut malformations. (A) Ventral views of normal counter-clockwise intestinal coiling of an NF stage 46 untreated control tadpole (top), and mild (middle) and severe (bottom) gut coiling malformations observed in sibling tadpoles exposed to 35 mg/L atrazine (DMSO) from NF stages 42 to 46. Arrows reflect direction of coiling; bars = 0.5 mm. (B) Incidence of gut coiling malformations observed in tadpoles exposed to 10, 25, or 35 mg/L atrazine or vehicle (DMSO) from NF stage 41, 42, or 43 through NF stage 46. Sample sizes are same as in Figure 1.*p < 0.05, and #p < 0.0001 as determined by post hoc pair-wise contrasts from logistic regression.
	Figure 4. Axis malformations and incidence of edema. (A) Lateral view of normal body axis in control NF stage 46 tadpole (top), and atrazine-exposed tadpoles exhibiting curved (middle) and severely shortened (bottom) axes. White arrows indicate edemas observed in the heart (middle) and gut (bottom) regions of atrazine-treated tadpoles. Bars = 1.0 mm. Incidence of axis malformations (B) and edemas (C) in tadpoles exposed to 10, 25, or 35 mg/L atrazine or vehicle (DMSO) from NF stage 41, 42, or 43 through NF stage 46. Sample sizes for (B) and (C) are same as in Figure 1.**p < 0.001, and #p < 0.0001 as determined by post hoc pair-wise contrasts from logistic regression.
	Figure 5. Level of apoptosis in the pronephric kidney and midbrain. (A) Dorsal view of tadpoles exhibiting kidney apoptosis phenotypes with corresponding scoring system (0 through 5). Pronephric kidneys are circled in white; the area of midbrain that was analyzed is demarcated in 1 by two white lines. Bars = 0.5 mm. (B) Kidney score (mean ± SE) after 12, 24, or 48 hr exposure to 10 or 35 mg/L atrazine or vehicle; data were analyzed using ordinal regression. (C) Number of apoptotic cells (mean ± SE) counted in the midbrain between the eyes and pronephric kidney after 12, 24, or 48 hr exposure to 10 or 35 mg/L atrazine or vehicle.p < 0.05, *p < 0.001, and #p < 0.0001 as determined by post hoc pair-wise contrasts.

References [+] :

Allran, Effects of atrazine on embryos, larvae, and adults of anuran amphibians. 2001, Pubmed