ABSTRACT
We examined the anogenital distance (AGD) plasticity in rats through the manipulation of the androgen environment in utero and during puberty. Dams were treated from gestation days 13-20 with vehicle, flutamide (20mg/kg/day), di-(2-ethylhexyl) phthalate (DEHP, 750mg/kg/day), or testosterone (1.0mg/kg/day). After weaning, male pups were randomly assigned to one of four postnatal groups, which received the same treatments given prenatally. Sixteen treatment groups were established based on the combination of pre- and postnatal exposures. The postnatal treatments were conducted from postnatal days 23-53. In utero flutamide and DEHP exposure significantly shortened male AGD, although this effect was more pronounced in flutamide-exposed rats. Postnatal flutamide, DEHP, and testosterone induced slight but significant reductions in male AGD. Our study indicates that AGD is a stable anatomical landmark that reflects the androgen action in utero, although it can also be slightly responsive to changes in the androgen environment following pubertal exposure.
Subject(s)
Androgen Antagonists/toxicity , Androgens/physiology , Penis/abnormalities , Prenatal Exposure Delayed Effects , Testis/abnormalities , Animals , Diethylhexyl Phthalate/toxicity , Disease Models, Animal , Dose-Response Relationship, Drug , Female , Flutamide/toxicity , Male , Organ Size/drug effects , Penis/drug effects , Pregnancy , Pregnancy Outcome , Rats , Spermatids/drug effects , Spermatids/metabolism , Testis/drug effects , Testosterone/biosynthesisABSTRACT
Data from in vitro studies suggest that the pesticides deltamethrin (D) and endosulfan (E) exert estrogen-like effects. There is concern that interaction between weakly estrogenic compounds can increase their estrogenic potency. The aim of the present study was to determine estrogenic activity in an animal model and the possible female reproductive adverse effects of these pesticides combined. Wistar rats received daily (po), from day 6 of pregnancy to day 21 of lactation, deltamethrin and endosulfan concomitantly: D: 2.0 mg/kg+E: 1.5 mg/kg, or D: 3.0 mg/kg+E: 2.0 mg/kg, or D: 4.0 mg/kg+E: 3.0mg/kg. Some offspring also were exposed directly after weaning. Maternal and reproductive outcome data were assessed. An uterotrophic assay to screen in vivo estrogenic activity of D+E was also performed. A group of female offspring was analyzed for vaginal opening (VO), first estrus, estrous cycle regularity, and weights of the uterus and ovaries. No signs of maternal toxicity were detected. Results from the uterotrophic assay indicate absence of in vivo estrogenic activity of D+E. No significant variations in reproductive endpoints of females were observed. These results suggest that administration of D+E does not pose a reproductive hazard to female rats exposed during critical periods of development, indicating that the combination does not exert estrogen-like effects in vivo or is not delivered to target organs.
