PARENT SESSION
MALE REPRODUCTIVE TRACT

Monday, August 2, 2004
10:30 AM–12:30 PM
Buchanan Courtyard

(171) NEONATAL EXPOSURE TO DI(N-BUTYL)PHTHALATE ALTERS MALE REPRODUCTIVE TRACT DEVELOPMENT.

Kim, Hyung Sik¹, Han, Soon Young ², Kim, Tae Sung², Shin, Jae-Ho², Moon, Hyun-Ju², Kang, Il Hyun², Kim, In Young², ¹ Laboratory of Molecular Toxicology, College of Pharmacy, Pusan National University, San 30, Jangjun-dong, Gumjung-ku, Pusan, Korea² National Institute of Toxicological Research, Korea Food and Drug Administration, Seoul, Korea

ABSTRACT- Previous investigators have shown that perinatal exposure to DBP alters testicular and accessory sex organ development in rats. However, there is no data on male reproductive tract alterations following neonatal exposure to DBP. This study was conducted to evaluate male reproductive organ development in early postnatal male rats following neonatal exposure to DBP and to identify the mechanism of action. Neonatal Sprague-Dawley male rats were injected subcutaneously from days 5 to 14 after birth with corn oil (control) and DBP (5, 10, and 20 mg/animal). Animals were killed at postnatal day (PND) 31 and PND 42, respectively, and testes, epididymis, seminal vesicles, ventral prostate, levator ani plus bulbocavernosus muscles (LABC), and cowpers glands were weighed. In addition, the expressions of androgen receptor (AR), estrogen receptors (ERs), and steroidogenic factor-1 (SF-1) were also examined in the testes. Total body weights gains were significantly reduced at PND 29-31, but gradually recovered on PND 42. However, DBP (20 mg/animal) significantly reduced the weights of testes and accessory sex organs (seminal vesicles, LABC, and cowpers glands), but not of the epididymis, versus the control on PND 31. These adverse effects persisted through puberty at PND 42. DBP also slightly delayed testis descent (bilateral) in a dose-dependent manner. Serum testosterone levels did not show any significant changes in the control and DBP treatment groups. Histomorphological examination showed mild diffuse Leydig cells hyperplasia in the interstitium of severely affected tubules on PND 31. Only a few multinuclear germ cells were observed. DBP (20 mg/animal) significantly decreased the expression of AR, whereas ER and SF-1 expressions were increased in a dose-dependent manner on PND 31 in the rat testes. On PND 42, DBP (20 mg/animal) significantly inhibited ER expression in the testes, but not AR, ER, and SF-1. These results demonstrate that neonatal exposure to DBP causes permanent changes in the endocrine system and results in abnormal male reproductive tract development up to puberty. Thus our data suggest that DBP is likely to exert its antiandrogenic actions through the disruption of AR or ER expression during the early neonatal stage.

KEY WORDS: Neonatal exposure, Antiandrogenic actions, Di(n-butyl)phthalate, Male reproductive organs