Influence of persistent thyroxine reduction on spermatogenesis in rats neonatally exposed to 2,2',4,4',5,5'-hexa-chlorobiphenyl.
BACKGROUND
The aim of the present study is to determine the long-term testicular effects of neonatal exposure to PCB153.


METHODS
Sprague-Dawley (SD) rats were treated by oral gavage with PCB153 in corn oil at doses of 0, 0.025, and 2.5 mg/kg per day from postnatal day 3 (PND 3) to PND7. The rats were sacrificed on PND 8 and PND 77. TUNEL in situ detection for testis apoptosis, immunohistochemical staining of thyroid gland for thyroxine (T4), semi-quantitative RT-PCR for mRNA expression, and radioimmunoassay (RIA) for serum hormone levels were performed.


RESULTS
Neonatal treatment with PCB153 at both doses had no obvious effects on body weight, testis weight, testis histology, and germ cell apoptosis, but decreased T4 staining in thyroid gland was observed on PND 8. On PND 77, neonatal treatment with 2.5 mg/kg per day of PCB153 significantly reduced daily sperm product (DSP). Serum levels of thyroxine (T4) and free thyroxine (FT4) decreased, but there were no differences in thyroid-stimulating hormone (TSH) level between the control and exposed groups. Gap junction connexin43 (CX43) and cyclin-dependent kinase inhibitor (CDKI) P27kip1 mRNA expression, which was associated with Sertoli cell differentiation, was significantly reduced after PCB153 treatment on PND 8 but not on PND 77. Androgen-binding protein (ABP) and androgen receptor (AR) mRNA expression, which indicates Sertoli cell maturation, was suppressed on PND 77 after neonatal PCB153 exposure.


CONCLUSIONS
The findings in this study suggest that neonatal exposure to PCB153 induces persistent T4 reduction, which disturbs Sertoli cell function, and subsequently results in alterations in adult spermatogenesis. Birth Defects Res (Part B) 89:18-25, 2010. (c) 2009 Wiley-Liss, Inc.
Xiao
Wusheng
W
School of Public Health, Fudan University, Shanghai, China.
Li
Keyong
K
Wu
Qing
Q
Nishimura
Noriko
N
Chang
Xiuli
X
Zhou
Zhijun
Z
D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis; D001713:Biphenyl Compounds / Q000633:toxicity*; D005260:Female; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling; D008297:Male; D018811:Maternal Exposure; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013091:Spermatogenesis / Q000187:drug effects*; D013963:Thyroid Hormones; D013974:Thyroxine / Q000737:chemistry*; D013997:Time Factors
D001713:Biphenyl Compounds; D013963:Thyroid Hormones; D011078:Polychlorinated Biphenyls; D013974:Thyroxine; C014024:2,4,5,2',4',5'-hexachlorobiphenyl