Interactive effects of TCDD and p,p'-DDE on male reproductive tract development in in utero and lactationally exposed rats.
The developing male rat reproductive system is highly sensitive to low doses of TCDD and p,p'-DDE (DDE), which exert antiandrogenic effects via different mechanisms. This study investigates the interactive effects of in utero and lactational exposure to a mixture of these compounds. Pregnant Holtzman rats received one of the following: vehicle on gestation day (GD) 14-18, 0.25 microgram/kg TCDD on GD15, 100 mg/kg DDE on GD 14-18, or 0.25 microgram/kg TCDD on GD15 and 100 mg/kg DDE on GD 14-18. Male offspring were euthanized on postnatal day (PND) 21 (weaning), PND 32 (prepuberty), PND 49 (puberty), and PND 63 (postpuberty). Coadministration of these doses of TCDD and DDE appeared to potentiate their individual actions on prostate weight on PND 21, while immunostaining for the prostatic androgen receptor exhibited patterns characteristic of the effects of both compounds individually. Cauda epididymal sperm number was reduced by each compound but was not further reduced by exposure to TCDD and DDE in combination. Anogenital distance, age at onset of puberty, daily sperm production, testicular and accessory sex organ weight (nonprostate), and levels of prostatic androgen-regulated gene transcripts are affected at higher doses of both compounds, but not at the doses used in the present study. Only DDE-treated animals retained nipples on PND 13. Serum androgen levels did not differ between treatment groups. In conclusion, the developing rat prostate is uniquely sensitive to the effects of TCDD and DDE, which may augment one another's effects in this organ.
Loeffler
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School of Pharmacy and Environmental Toxicology Center, University of Wisconsin, Madison, Wisconsin, 53706, USA.
Peterson
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D000728:Androgens / Q000097:blood; D000818:Animals; D003633:Dichlorodiphenyl Dichloroethylene / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004785:Environmental Pollutants / Q000494:pharmacology; D005260:Female; D005837:Genitalia, Male / Q000187:drug effects* / Q000196:embryology / Q000254:growth & development; D007150:Immunohistochemistry; D007306:Insecticides / Q000494:pharmacology*; D007774:Lactation; D008297:Male; D008431:Maternal-Fetal Exchange; D000072317:Polychlorinated Dibenzodioxins / Q000008:administration & dosage / Q000494:pharmacology*; D011247:Pregnancy; D011467:Prostate / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000032:analysis; D013076:Sperm Count
D000728:Androgens; D004785:Environmental Pollutants; D007306:Insecticides; D000072317:Polychlorinated Dibenzodioxins; D011944:Receptors, Androgen; D003633:Dichlorodiphenyl Dichloroethylene