title: Developmental exposure to chlorpyrifos induces alterations in thyroid and thyroid hormone levels without other toxicity signs in CD-1 mice.
abstract: Organophosphorus insecticides, as Chlorpyrifos (CPF), are widely used in agriculture and against household pests; these compounds receive an increasing consideration as potential endocrine disrupters. The aim of the present study was to examine the potential short- and long-term effects of CPF on thyroid and adrenal glands in CD1 mice following exposure at dose levels not inducing brain acetyl cholinesterase (AchE) inhibition, during gestational and/or postnatal vulnerable phases. Pregnant dams were treated with 0, 3, 6 mg/kg bw/day of CPF on gestational days 15-18. After delivery, pups were treated subcutaneously on postnatal days (PND) 11-14 with: 0, 1, 3 mg/kg bw/day of CPF. Serum thyroxin (T4), thyroid and adrenals histology and histomorphometry were evaluated in dams and in F1 mice. In dams at 6 mg/kg, decreased T4 levels and increased cell height in thyroid were observed, and adrenal histology showed a slightly increased vacuolization in the X-zone. In the F1, short-term morphological modifications (reduced follicular size at PND 2) and long-term morphological (increased necrotic follicular cells) and biochemical alterations (reduced serum T4 levels) were found at PND 150 with an apparent higher vulnerability of males. For the first time these results indicate that CPF exposure at dose levels not inducing brain AchE inhibition causes thyroid alterations in dams and in F1 CD1 mice. Thyroid may be a sensitive target to CPF developmental exposure possibly leading to long-term effects on thyroid function. Because thyroid plays a pivotal role in mammalian development, these findings can be relevant to humans.
authors.affiliation: Department of Cellular Biology and Neuroscience, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: De Angelis
authors.forename: Roberta
authors.initials: R
authors.lastname: Tassinari
authors.forename: Francesca
authors.initials: F
authors.lastname: Maranghi
authors.forename: Agostino
authors.initials: A
authors.lastname: Eusepi
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Virgilio
authors.forename: Flavia
authors.initials: F
authors.lastname: Chiarotti
authors.forename: Laura
authors.initials: L
authors.lastname: Ricceri
authors.forename: Aldina
authors.initials: A
authors.lastname: Venerosi Pesciolini
authors.forename: Enzo
authors.initials: E
authors.lastname: Gilardi
authors.forename: Gabriele
authors.initials: G
authors.lastname: Moracci
authors.forename: Gemma
authors.initials: G
authors.lastname: Calamandrei
authors.forename: Antonella
authors.initials: A
authors.lastname: Olivieri
authors.forename: Alberto
authors.initials: A
authors.lastname: Mantovani
mesh_terms: D000307:Adrenal Gland Diseases / Q000139:chemically induced / Q000473:pathology; D000311:Adrenal Glands / Q000254:growth & development / Q000473:pathology; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D004390:Chlorpyrifos / Q000633:toxicity*; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D052244:Endocrine Disruptors / Q000633:toxicity*; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D005260:Female; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D051379:Mice; D011247:Pregnancy; D013961:Thyroid Gland / Q000254:growth & development* / Q000378:metabolism / Q000473:pathology; D013963:Thyroid Hormones / Q000096:biosynthesis*; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
chemical_list: D002800:Cholinesterase Inhibitors; D052244:Endocrine Disruptors; D007306:Insecticides; D013963:Thyroid Hormones; D014284:Triiodothyronine; D004390:Chlorpyrifos; D013974:Thyroxine