Dietary ethinyl estradiol exposure during development causes increased voluntary sodium intake and mild maternal and offspring toxicity in rats.
Exogenous estrogen exposure during development often results in behavioral masculinization and/or defeminization of genetic females. Genetic males may be defeminized, hypermasculinized or even demasculinized after similar treatment. Here, pregnant Sprague-Dawley rats consumed phytoestrogen-free diets containing 0, 1, 5 or 200 ppb EE(2) beginning on gestational day (GD) 7. Offspring were weaned to the same maternal diet and maintained gonadally intact. There were mild effects on body weight and food consumption in dams of the 200 ppb group and their offspring weighed less at birth than those of the control group; however, gross assessments of nursing behavior were normal in all dietary groups. Postweaning, offspring of the 200 ppb group weighed less and consumed less food than controls. There were no EE(2)-related effects on open-field activity (tested at postnatal days (PND) 22-24, 43-45 and 64-66), play behavior (tested at PND 35), running wheel activity (PND 63-77) or intake of a 0.3% saccharin-flavored solution (PND 69-71). Intake of a 3.0% sodium chloride-flavored solution on PND 73-75 was increased in both male and female offspring of the 200 ppb group relative to same-sex controls, an effect that is reportedly estrogen mediated. Sodium chloride-flavored solution intake is a sexually dimorphic behavior for which female rats consume more than males. Here, while EE(2) exposure had few effects on the conventional tests of sexually dimorphic behaviors, exposure to 200 ppb in the diet appeared to feminize genetic males and hyperfeminize genetic females with regard to sodium intake.
Ferguson
Sherry A
SA
HFT-132/Division of Neurotoxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA. sferguson@nctr.fda.gov
Delclos
K Barry
KB
Newbold
Retha R
RR
Flynn
Katherine M
KM
D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D004044:Dietary Proteins; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects*; D045166:Estradiol Congeners / Q000633:toxicity*; D004997:Ethinyl Estradiol / Q000633:toxicity*; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D005518:Food Preferences; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012439:Saccharin; D012727:Sex Characteristics; D012964:Sodium / Q000378:metabolism*
D004044:Dietary Proteins; D045166:Estradiol Congeners; D004997:Ethinyl Estradiol; D012964:Sodium; D012439:Saccharin