Exposure of cynomolgus monkey embryos to retinoic acid causes thymic defects: effects on peripheral lymphoid organ development.
We have previously reported that exposure of monkey embryos to 13-cis-retinoic acid (cRA) results in thymic defects. In this study, we analyzed lymphocyte and antigen-presenting cell populations at gestational days (GDs) 80-100 in the thymus, spleen, mesenteric lymph nodes, and gut-associated lymphoid tissue following a teratogenic dosing regimen of cRA (2.5 and 5 mg/kg) at GD14-27. Tissue sections were immunostained for T-cells (anti-CD3), B-cells (anti-CD20), dendritic cells (p55), and major histocompatibility class II (anti-HLA-DR). Digital images of spleen sections were analyzed to obtain the relative area occupied by the cell subsets within the white pulp (WP). Compared with controls, the T-cell dependent compartment of the spleen WP in specimens with perturbed thymic development (aplasia and severe hypoplasia) showed a reduction in size and proportion of CD3(+) T cells. Our findings indicate that cRA-induced thymic defects result in disrupted development of the splenic T-cell dependent compartment.
Makori
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California Regional Primate Research Center, University of California, Davis, CA 95616-8542, USA.
Peterson
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PE
Lantz
K
K
Hendrickx
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AG
D000014:Abnormalities, Drug-Induced / Q000662:veterinary*; D000818:Animals; D017252:CD3 Complex; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D007150:Immunohistochemistry; D015474:Isotretinoin / Q000009:adverse effects*; D008252:Macaca fascicularis / Q000196:embryology*; D011247:Pregnancy; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000002:abnormalities* / Q000187:drug effects* / Q000196:embryology
D017252:CD3 Complex; D015474:Isotretinoin