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EFFECTS OF PRENATAL TESTOSTERONE PROPIONATE AND VINCLOZOLIN ON PERINATAL AND INFANTILE DEVELOPMENT OF MALE AND FEMALE RATS
Citation:
Wolf, C J., J. R. Furr, G. A. LeBlanc, AND L E. Gray Jr. EFFECTS OF PRENATAL TESTOSTERONE PROPIONATE AND VINCLOZOLIN ON PERINATAL AND INFANTILE DEVELOPMENT OF MALE AND FEMALE RATS. Presented at Society of Toxicology, Nashville, TN, March 17-21, 2002.
Description:
Effects of Prenatal Testosterone Propionate and Vinclozolin on Perinatal and Infantile Development of Male and Female Rats
Cynthia Wolf1,2, Jonathan Furr1, Gerald A. LeBlanc2, and L. Earl Gray, Jr.1
1USEPA, NHEERL, RTD, EB, RTP, NC 27711, 2Dept. of Environmental and Molecular and Toxicology, NCSU, Raleigh, NC 27695
Prenatal exposure to both androgenic and antiandrogenic chemicals can adversely effect pregnancy and growth of offspring, but have opposite effects on sexual development. We conducted a study to determine whether an antiandrogenic chemical, vinclozolin (V), and an androgenic chemical, testosterone propionate (TP), in combination or alone, have similar or opposing effects on perinatal health and reproductive development. Sprague-Dawley rat dams were dosed on gestational day (GD) 14 (GD 1 = day of plug) to GD 19 with either corn oil (vehicle, orally), V (200 mg/kg, orally), TP (1 mg/rat, sc injection), or V+TP. Weight gain in dams through the dosing period was reduced by V (35.4 g, p < 0.05 vs. 53.1 g in controls) and by TP (28.1g ; p <0.005) but was further reduced by V+TP (21.9 g, p < 0.0005). Live litter size on postnatal day (PND) 2 was reduced by V+T only (5.6, p < 0.001 vs 13.8 in controls), although mean number of uterine implantation sites was not affected. Anogenital distance (AGD) in females on PND 2 was increased from control values (1.73mm) by TP (2.51mm; p <0.0001) and restored by co-administration of V (1.62). AGD in males was reduced from control values (4.04 mm) by V (2.18; p <0.0001), but this reduction was not antagonized by co-administration of TP (2.07mm). Number of areolas on PND 14 in females was reduced from control values (12.05) by TP (3.69; p < 0.0001) and fully restored by V. Areolas were induced by V in males and co-administration of TP partially attenuated the prominence of the areolas (score = 23, scored by prominence on a scale of 1 - 36 per pup; p < 0.0001) compared to those in the V group (score = 30). We conclude that 1) V and TP are additive in maternal and pup health, 2) V attenuates the androgenic effects of TP on AGD and areolas in the female rat offspring, but 3) the dose of TP used here does not fully attenuate the antiandrogenic effects of V on AGD and areolas in male rat offspring. This abstract does not necessarily reflect USEPA policy.