Effects of in utero exposure to di(2-ethylhexyl) phthalate on sexual development in female offspring

Abstract

To evaluate the ability of di(2-ethylhexyl) phthalate (DEHP) with inducing damage in sexual development of female offspring rats after maternal exposure. On gestational day (GD) 12, pregnant Wistar rats were weighed, encoded and randomly assigned to 5 groups (10 dams per group). From GD 12 through GD 17 each dam was dosed daily by gavage with either corn oil (vehicle control, 1 mgxkg(-1)xd(-1)) or DEHP (1, 250, 750 and 1000 mgxkg(-1)xd(-1)). Then female offspring were monitored for eye opening on postnatal day (PND) 14-17, organ coefficient on PND 22 and the time to vaginal opening on PND 30 - 38 (if vagina did not open during the period, observation time should extent to adult), as well as body weight, time to first estrus. No significant changes were observed on eye opening at any dose, which were (15.8 +/- 0.4) d, (16.3 +/- 0.6) d, (16.0 +/- 0.6) d, (15.9 +/- 0.6) d, (15.8 +/- 0.4) d respectively in control, 1, 250, 750 and 1000 mgxkg(-1)xd(-1) (F = 1.363, P = 0.262). However, 62.50% (15/24), 81.25% (26/32) female offspring were permanently absence of vaginal orifice in 750 and 1000 mgxkg(-1)xd(-1) groups respectively, while control, 1 and 250 mgxkg(-1)xd(-1) groups developed normally with vaginal orifices (chi(2) values were 84.92, 132.79, respectively, P < 0.01). The ages of vaginal opening were (32.7 +/- 1.3) d, (33.3 +/- 1.5) d, (32.2 +/- 1.5) d, (33.1 +/- 1.3) d, (33.3 +/- 1.2) d and the body weight were (91.56 +/- 6.65) g, (93.79 +/- 6.28) g, (92.98 +/- 8.48) g, (100.57 +/- 6.47) g, (103.83 +/- 8.24) g in control, 1, 250, 750 and 1000 mgxkg(-1)xd(-1). After covariance adjustment for body weight, which can statistically influenced the age of vaginal opening (F = 40.857, P < 0.05), difference were found at the age of vaginal opening (F = 3.075, P < 0.05), and 250 mgxkg(-1)xd(-1) group was advanced than control (t = -2.056, P < 0.05). Exposure to DEHP in utero from GD 12 - 17 can result in abnormalities of sexual development such as the time to vaginal opening and vaginal atresia.