title: Preliminary investigation of changes in the sexually dimorphic nucleus of the rat medial preoptic area following prenatal exposure to fenitrothion.
abstract: In vitro, the organophosphate insecticide fenitrothion is a potent competitive androgen receptor antagonist, whereas in vivo it affects the development of the male rat reproductive system. The purpose of this pilot study was to determine whether prenatal exposure to fenitrothion affects development of the rat sexually dimorphic nucleus of the medial preoptic area (SDN-POA). Pregnant rats (n = 5-6 litters/group) were orally dosed with corn oil (vehicle) or fenitrothion (20 or 25 mg kg(-1) day(-1)) from gestation day (GD) 12-21. Offspring were euthanized after reaching sexual maturity (females 60-65 days old and males 96-105 days old) and the SDN-POA volumes determined for two rats/sex/litter. Tremors, increased lacrimation and decreased body weight gain were observed in dams from both fenitrothion exposure groups. Reproductive effects in male offspring, including reduced anogenital distance on postnatal day (PND) 1 and increased retention of areolae (PND 13) were observed following fenitrothion exposure at these dose levels. These effects did not persist into adulthood. There was a dose-related increase in the SDN-POA volume in males and a dose-related decrease in SDN-POA volume in females exposed to fenitrothion. These SDN-POA volume changes contrast with those seen with flutamide, another potent anti-androgen, and suggest that fenitrothion may have mixed endocrine effects on the developing brain.
authors.affiliation: CIIT Centers for Health Research, The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709-2137, USA. mstruve@thehammer.org
authors.forename: Melanie F
authors.initials: MF
authors.lastname: Struve
authors.forename: Katie J
authors.initials: KJ
authors.lastname: Turner
authors.forename: David C
authors.initials: DC
authors.lastname: Dorman
mesh_terms: D000284:Administration, Oral; D000726:Androgen Antagonists / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005278:Fenitrothion / Q000008:administration & dosage / Q000633:toxicity*; D005684:Gait / Q000187:drug effects; D007306:Insecticides / Q000008:administration & dosage / Q000633:toxicity*; D007765:Lacrimal Apparatus / Q000187:drug effects / Q000378:metabolism; D008098:Litter Size / Q000187:drug effects; D008297:Male; D010865:Pilot Projects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011301:Preoptic Area / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology; D051381:Rats; D012741:Sexual Maturation; D013666:Tears / Q000378:metabolism; D014202:Tremor / Q000139:chemically induced
chemical_list: D000726:Androgen Antagonists; D002800:Cholinesterase Inhibitors; D007306:Insecticides; D005278:Fenitrothion