title: Reproductive toxicity of linuron following gestational exposure in rats and underlying mechanisms.
abstract: Linuron is a widely used herbicide in agriculture; its endocrine disruptive toxicity has recently received public attention. This study was designed to examine the developmental toxicity of linuron on the reproductive system of male offspring following maternal exposure. Mother rats received oral gavages of linuron, once daily, at the dose of 0, 50, 100, 150 or 200mg/kg, from gestational day (GD)13 to GD18; gonadal organs from GD20 fetuses were examined. Data indicated that exposed male offspring had a significantly shortened anogenital distance. Pathological examination further revealed a lack of fusion in the urogenital fold in treated fetuses, the damaged seminiferous tubules, and the injured Leydig cell ultrastructure. Analysis of serum testosterone concentrations at postnatal day (PND)2 showed a significant dose-related reduction (about 33.7-58.75%, r=-0.838, p<0.05) as compared to controls. Immunohistochemical results demonstrated a significantly reduced expression of enzymes pertinent to the testosterone production including P450scc, 3β-HSD, and PCNA in Leydig cells (p<0.05). qPCR studies confirmed decreased levels of mRNAs encoding P450scc, 3β-HSD and PCNA (p<0.05). Taken together, these data suggest that maternal exposure to linuron hampers the male gonadal organ development; this appears to be due to linuron's direct action on the production of testosterone in fetal and postnatal offspring.
authors.affiliation: Department of Hygiene Toxicology, School of Public Health, Zunyi Medical College, Zunyi, Guizhou, PR China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Ding
authors.affiliation: School of Health Sciences, Purdue University, West Lafayette, IN, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Department of Hygiene Toxicology, School of Public Health, Zunyi Medical College, Zunyi, Guizhou, PR China.
authors.forename: Hua
authors.initials: H
authors.lastname: Han
authors.affiliation: Department of Hygiene Toxicology, School of Public Health, Zunyi Medical College, Zunyi, Guizhou, PR China.
authors.forename: Xiyin
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Hygiene Toxicology, School of Public Health, Zunyi Medical College, Zunyi, Guizhou, PR China.
authors.forename: Binli
authors.initials: B
authors.lastname: Hu
authors.affiliation: Department of Hygiene Toxicology, School of Public Health, Zunyi Medical College, Zunyi, Guizhou, PR China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Hygiene Toxicology, School of Public Health, Zunyi Medical College, Zunyi, Guizhou, PR China.
authors.forename: Liyu
authors.initials: L
authors.lastname: Su
authors.affiliation: Department of Hygiene Toxicology, School of Public Health, Zunyi Medical College, Zunyi, Guizhou, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Hygiene Toxicology, School of Public Health, Zunyi Medical College, Zunyi, Guizhou, PR China. Electronic address: liyan067321@sina.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004305:Dose-Response Relationship, Drug; D005260:Female; D005837:Genitalia, Male / Q000187:drug effects; D006540:Herbicides / Q000008:administration & dosage / Q000633:toxicity*; D008044:Linuron / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000097:blood
chemical_list: D006540:Herbicides; D008044:Linuron; D013739:Testosterone
keywords: Developmental toxicity; Fetus; Leydig cells; Linuron; Offspring; Reproductive toxicity; Testosterone