Effects of in Utero and Lactational Exposure to Di(2-ethylhexyl)phthalate on Somatic and Physical Development in Rat Offspring

Abstract

Di(2-ethylhexyl)phthalate (DEHP) has been reported to act as an antiandrogen and to affect the reproductive organs and accessory genital glands. Thus, to assess the reproductive toxicity of DEHP it is important to examine both its adverse effects on the development of offspring following maternal exposure and its effects on sexual function and fertility. In the present study, we examined whether in utero and lactational exposure to DEHP affects postnatal somatic growth of offspring in the rat. Pregnant females were orally administered various doses of DEHP (0, 25, 100 or 400 mg/kg body weight/day) from gestational day (GD) 6 through postnatal day (PND) 20. There were no significant changes in body weight, body length, tail length, or the weight of individual organs between the control and DEHP-treated groups. Somatic hormonal parameters were the same for all DEHP doses. These findings suggest that in utero and lactational exposure to various concentrations of DEHP has very little effect on postnatal development or endocrine and physical status of male and female rat offspring under the experimental conditions of the present study.Key words: Di(2-ethylhexyl)phthalate, Postnatal development, In utero and lactational exposure, Offspring, Rat excluded from many products to avoid consumer exposure. However, recent heightened public concerns about environmental exposure to high concentrations of DEHP have raised new questions about its possible occupational and medical health hazards.Developmental toxicity studies of DEHP have been conducted in laboratory mice [4][5][6][7][8] and rats [8][9][10] . These reports suggest that in utero exposure to high doses of DEHP induces embryotoxicity and/or teratogenicity. Animal reproductive toxicity studies of DEHP have also been reported. In a study of adult male rats, testicular defects such as atrophy of the seminiferous tubules, loss of spermatogenesis and vacuolation of Sertoli cells were observed after 90 days of dietary exposure to DEHP at 500 and 5,000 ppm (equivalent to 37.6 and 375.2 mg/kg/day, respectively) 11) . Perinatal exposure to DEHP in rats from gestational day (GD) 14 through postnatal day (PND) 3 reduced anogenital distance, testis weight or the weight of androgen-dependent tissues 12) .

In utero exposure to the endocrine disruptor di-(2-ethylhexyl) phthalate promotes local adipose and systemic inflammation in adult male offspring

“…32, 33 Evidence supporting this hypothesis was observed by Schmidt et al 33 in their findings that exposing mice to a diet containing low doses (0.05 and 5 mg DEHP per kg per day, corresponding to a daily intake of 0.00102 and 0.108 DEHP per kg per day) of DEHP in utero and during lactation resulted in increased visceral fat and body weight in adult offspring. In agreement with previous work in rats, 13, 35 we did not observe changes in total body weight. It remains to be determined whether a differential fat distribution is induced by DEHP without modifying the total weight of the animals and whether more drastic changes would develop later in time during senescence.…”

Differential Effects of Flutamide and Di-(2-ethylhexyl) phthalate on Male Reproductive Organs in a Rat Model

“…We demonstrated in this study that DEHP and Flu interfered with the development of reproductive organs in a dose-dependent manner, in agreement with previous reports [12,26]. A decrease in the testicular, epididymal and prostate weights was caused by in utero Flu exposure.…”

“…In this study, in utero exposure to DEHP and Flu caused an increase in the number of nipples and /or areolae in a dose-dependent manner. Our results are in agreement with the previous reports [22,25].We demonstrated in this study that DEHP and Flu interfered with the development of reproductive organs in a dose-dependent manner, in agreement with previous reports [12,26]. A decrease in the testicular, epididymal and prostate weights was caused by in utero Flu exposure.…”

In Utero and Lactational Exposures to Diethylhexyl-Phthalate Affect Two Populations of Leydig Cells in Male Long-Evans Rats1

“…The weight of the seminal vesicle plus coagulating glands (androgen-dependent tissues) in adult rats was also significantly reduced after exposure to 475 mg/kg DEHP, although only this dose caused significant serum testosterone levels [38]. Doses below 400 mg/kg DEHP had no effects on weights of these androgen-dependent organs and testosterone levels [38,41]. However, the gene profiles of in utero and lactational exposures to DEHP in our study were a little bit different from those reported by Culty et al [34].…”