Effects of di(2-ethylhexyl) phthalate on the gonadal pathophysiology, sperm morphology, and reproductive performance of male rats.

Abstract

Dietary exposure of adult male F344 rats to 0, 320, 1250, 5000, or 20,000 ppm DEHP for 60 consecutive days resulted in a dose-dependent reduction in total body, testis, epididymis, and prostate weights at 5000 and 20,000 ppm. Degenerative changes were observed in testis, along with decreased testicular zinc content, reduced epididymal sperm density and motility, and increased occurrence of abnormal sperm at 20,000 ppm. There was a trend towards reduced testosterone and increased luteinizing hormone and follicle stimulating hormone in serum at 5000 and 20,000 ppm. The mean percentage of fertile animals was unchanged and reduction in fertility parameters, although not marked in severity, were correlated with gonadal effects. Average litter size was reduced at 20,000 ppm, but initial pup weights and growth were unaffected. There were no grossly observed abnormalities in the offspring and the rate of neonatal deaths was similar in control and DEHP treated groups. Characteristic toxicity manifestations of DEHP included dose-dependent enlargement of liver and reduced sperm triglycerides and cholesterol. Additionally, serum albumin and total proteins were dose dependently increased upon treatment with DEHP. Cessation of exposure to DEHP initiated partial to complete recovery from toxicity in most cases. The magnitude of recovery were variable with that ofthe gonads being slower than other systems. These data suggest a lack of reproductive dysfunction in F344 male rats at DEHP doses below 20,000 ppm which produced measurable testicular degeneration and afflicted epididymal sperm morphology under the present experimental conditions.

Expression Pattern of Sulfated Glycoprotein-2 (SGP-2) mRNA in Rat Testes Exposed to Endocrine Disruptors

“…This finding is consistent with previous reports that perinatal exposure of male rats to DEHP produces adverse effects in androgenresponsive tissues [32]. Specifically, 2,000 mg/kg/ day DEHP has been previously shown to cause testicular atrophy [24], damage to the seminiferous epithelium [33] and reduced epididymal sperm density and motility [34] in rats.…”

Differential Expression of 3.BETA.-Hydroxysteroid Dehydrogenase mRNA in Rat Testes Exposed to Endocrine Disruptors

“…It also reduces testicular T production in vivo and T levels in the testis [21]. Other studies have reported that exposure of rats to DEHP (200 mg/kg/day) causes various effects, including a 77% decrease in the activity of the steroidogenesis enzyme 17β-hydroxysteroid dehydrogenase, a 50% reduction in T production in Leydig cells [22], enhanced testosterone 5α-reductase (T5α-R) activity in the testis [23], and reduced epididymal sperm density and motility [24].…”

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

“…It has been estimated that mean DEHP intake is 8.2 µg/kg body weight per day for adults 3) . During recent years, DEHP has been Dietary exposure of adult male rats given 0, 320, 1,250, 5,000, and 20,000 ppm DEHP (equivalent to 0, 17.5, 69.2, 284.1 and 1156.4 mg/kg/day, respectively) for 60 days, when mated with untreated adult females, did not affect the rate of neonatal death, initial pup weight or growth (up to PND 7), whereas the average litter size decreased in rats fed 20,000 ppm DEHP 13) . Inhalation exposure of adult male Wistar rats to 25 mg/m 3 for 6 h/day for 8 wk increased plasma testosterone level and seminal vesicle weight in a dosedependent manner 14) .…”