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Abstract

Biphasic effects of postnatal exposure to diethylhexylphthalate on the timing of puberty in male rats 
Ge,Renshan; Chen,Guo-Rong; Dong,Qiang; Akingbemi,Benson T.; Sottas,Chantal M.; Santos,Michelle; Sealfon,Stuart C.; Bernard,Daniel J.; Hardy,Matthew P.
Journal of Andrology 28(4): 513-520
Publication date: 2007


Phthalate esters such as di(2-ethylhexyl)phthalate (DEHP), whichare commonly found in cosmetics and in flexible plastics distributedby the food, construction, and medical products industries,have been classified as anti-androgens. High-dose DEHP exposurein utero is associated with decreased androgen levels. However,when administered after birth, low doses of DEHP (eg, 10 mg/kgbody weight) may stimulate androgen production. In the presentstudy, the potential of phthalate exposure to advance or delaythe timing of puberty was assessed. Male Long-Evans rat pupswere chronically subjected to low or high doses of DEHP, withthe androgen-driven process of preputial separation servingas an index of pubertal timing. Rats were treated with 0, 10,500, or 750 mg/kg body weight DEHP for 28 days starting at day21 postpartum. The average age at which the animals completedpreputial separation was measured in each group. The age ofpreputial separation was 41.5 ± 0.1 days postpartumin controls (vehicle). The 10 mg/kg DEHP dose advanced pubertalonset significantly to 39.7 ± 0.1 days postpartum, whereasthe 750 mg/kg DEHP dose delayed pubertal onset to 46.3 ±0.1 days postpartum. The 10 mg/kg DEHP dose also significantlyincreased serum testosterone (T) levels (3.13 ± 0.37ng/mL) and seminal vesicle weights (0.33 ± 0.02 g) comparedwith control serum T (1.98 ± 0.20 ng/mL) and seminalvesicle weight (0.26 ± 0.02 g), while the 750 mg/kgdose decreased serum T (1.18 ± 0.18 ng/mL) as well astestes and body weights. Direct action of the DEHP metabolite,monoethylhexylphthalate (MEHP), on Leydig cell steroidogeniccapacity was investigated in vitro. MEHP treatment at a lowconcentration (100 µM) increased luteinizing hormone-stimulatedT production, whereas 10 mM concentrations were inhibitory.In conclusion, data from the present study indicate that DEHPhas a biphasic effect on Leydig cell function, with low-doseexposure advancing the onset of puberty. High doses of DEHP,which are anti-androgenic, may also be outside the range ofreal environmental exposure levels.