PURPOSE: Exposure of male reproductive organs to 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) has been reported to cause developmental changes. In this study, we evaluated the effects of in utero TCDD exposure on male reproductive development. MATERIALS AND METHODS: Pregnant C57BL/6 mice were administered a single intraperitoneal injection of TCDD (1microgram/kg) on gestation day (GD) 15. The offspring were examined in the immature stage on postnatal day (PND) 30 and in the mature stage on PND 60. The testes were examined for histological changes, androgen receptor (AR), proliferating cell nuclear antigen (PCNA) and apoptosis following the measurement of morphological changes. RESULTS: Anogenital distance (AGD) and testis weights were reduced by TCDD exposure both on PND 30 and PND 60 while body weights and length of male offspring were not affected by TCDD. The regular sperm developmental stage was impaired with TCDD treatment on PND 30. However, no difference was found between the control group and TCDD groups on PND 60. Simultaneously, the expression of AR was also reduced on PND 30, while it was increased on PND 60 compared with the control group. The expression of PCNA was decreased whereas apoptosis was not affected by TCDD both on PND 30 and PND 60. CONCLUSION: These results suggest that in utero exposure to TCDD influences the development of testes by inhibiting the expression of AR and PCNA. Moreover, the adverse effects of TCDD on male offspring reduced over time.
Animals ; Apoptosis/drug effects ; Cell Proliferation ; Embryonic Development/*drug effects ; Environmental Pollutants/*toxicity ; Female ; Male ; *Maternal Exposure ; Mice ; Mice, Inbred C57BL ; Organ Size/drug effects ; Pregnancy ; Receptors, Androgen/metabolism ; Testis/*drug effects/embryology/pathology ; Tetrachlorodibenzodioxin/*toxicity

OBJECTIVETo investigate the effect of nonylphenol (NP) exposure on the genital development of fetal male rats in pregnant rats, and to measure the mRNA and protein expression of insulin-like factor3 (Insl-3) in the testicular tissue of fetal rats.

METHODSA total of 100 pregnant SD rats were equally assigned to blank control group and four NP treated groups. Each rat in the NP treated groups received intragastric administration of NP at doses of 5, 40, 100, or 200 mg/kg/d from day 14 to 19 of gestation, and the rats in the blank control group received intragastric administration of pure peanut oil. The pregnant rats were sacrificed on day 19 of gestation. The body weight and testicular weight of each fetal rat were measured, and the descent of testis was also observed. The mRNA and protein expression of Insl-3 in the testicular tissue of fetal rats was analyzed by reverse transcription-PCR and Western blot.

RESULTSCompared with the blank control group, the 40, 100, and 200 mg/kg NP treated groups showed significantly decreased body weight and weight coefficient of testis (P < 0.05 or P < 0.01), significantly decreased testicular descent (P < 0.05), and significantly decreased mRNA and protein expression of Insl-3 (P < 0.05 or P < 0.01).

CONCLUSIONExposure to nonylphenol can lead to testicular maldevelopment, incomplete testicular descent, and Insl-3 expression downregulation of fetal male rats in pregnant rats.

Animals ; Body Weight ; Female ; Fetal Development ; drug effects ; Insulin ; metabolism ; Male ; Maternal Exposure ; adverse effects ; Organ Size ; Phenols ; toxicity ; Pregnancy ; Proteins ; metabolism ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley ; Testis ; drug effects ; embryology ; pathology