Effects of aroclor 1254 on the expression of the KAP3 gene and reproductive function in rats.
The present study investigated the effects of aroclor 1254 (A1254) on the expression of the kinesin superfamily associated protein 3 (KAP3) gene in F1 rat brain during brain sexual differentiation and puberty. In addition, the effects of A1254 on reproductive function were examined. The KAP3 gene is involved in the neurogenesis and synaptogenesis of sexual differentiation in rats and also during puberty. In the present study, pregnant Sprague-Dawley rats each received a daily dose of A1254 (0, 10, 50 mg kg(-1)) dissolved in 1.0 mL corn oil by gavage, from gestational Day (GD) 8 to postnatal Day (PD) 21. The mRNA levels of the KAP3 gene in hypothalamic tissues were analysed by northern blot hybridisation during the critical periods of brain sexual differentiation (GD18 and PD5) and puberty (PD28). Variables affecting reproduction in F1 female rats, such as vaginal opening (VO), vaginal oestrus (VE) and oestrous cyclicity, were recorded. Depending on the sex and A1254 exposure (control or 50 mg kg(-1) day(-1)), F1 rats were divided into three mating groups, namely control male-control female, control male-A1254-treated female and A1254-treated male-control female. During the critical periods of brain sexual differentiation (GD18, PD5) and puberty (PD28), KAP3 mRNA levels were significantly reduced in A1254-treated fetal and pubertal rat brains relative to those of control groups. In A1254-treated F1 female rats, VO and VE were delayed, the percentage of irregular oestrous cycles was increased and the duration of the oestrous cycle was extended in a dose-dependent manner compared with control groups. Treatment with a high dose of A1254 significantly impaired the reproductive function of both male and female F1 rats, including mating and pregnancy indices and the number of live fetuses. These data suggest that A1254 disrupts transcriptional regulation of the KAP3 gene in fetal and pubertal rat brains and that these effects may be related to A1254-induced abnormal brain sexual differentiation and lowered reproductive function in F1 rats.
Lee
Chae Kwan
CK
Institute of Industrial Medicine, Department of Occupational and Environmental Medicine, Busan Paik Hospital, Inje University, Busan 614-735, South Korea.
Kang
Han Seung
HS
Kim
Ju Ran
JR
Lee
Byung Ju
BJ
Lee
Jong Tae
JT
Kim
Jeong Ho
JH
Kim
Dae Hwan
DH
Lee
Chang Hee
CH
Ahn
Jin Hong
JH
Lee
Chae Un
CU
Yu
Seong Jin
SJ
Kang
Sung Goo
SG
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D020111:Chlorodiphenyl (54% Chlorine) / Q000494:pharmacology*; D030762:Estrous Cycle / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects* / Q000235:genetics; D012733:Sex Differentiation / Q000187:drug effects* / Q000235:genetics; D012741:Sexual Maturation / Q000187:drug effects / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects*; D014621:Vagina / Q000254:growth & development
D020662:Guanine Nucleotide Exchange Factors; D012333:RNA, Messenger; C515969:smgGDS protein, rat; D020111:Chlorodiphenyl (54% Chlorine)