Attenuation of cell cycle progression by 2,3,7,8-tetrachlorodibenzo-p-dioxin eliciting ovulatory blockade in gonadotropin-primed immature rats.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) reduces ovulation rate in rats. The present study was to investigate whether TCDD alters the progression of cell cycle, and thus resulting in the blockade of ovulation in gonadotropin-primed, immature rats. The ovulation rate and ovarian weight were reduced in intact rats given TCDD (32 µg/kg BW in corn oil) by gavage one day before pregnant mare's serum gonadotropin (PMSG; 5 IU/rat) injection. Flow cytometry demonstrated that the percentage of granulosa cells in S-phase was increased at 24 h following PMSG treatment, but declined at 8 h following hCG treatment in corn oil-treated rats. Interestingly, the number of S-phase cells in TCDD-treated rats was reduced 24 and 48 h following PMSG treatment. TCDD, however, increased the percentage of cells in G2/M-phase at 24 h following PMSG treatment. TCDD inhibited the mRNA levels of Cdk2 at 0 h and 24 h, and cyclin D2 at 24 h and 48 h following PMSG treatment. Protein levels of aryl hydrocarbon receptor in granulosa cells were elevated in TCDD-treated rats at 12 h and 24 h following PMSG treatment. The present study indicates that TCDD reduces S-phase cells and inhibits levels of Cdk2 and cyclin D2 at 24 h following PMSG treatment, implying the ovulation-inhibiting action of TCDD may be exerted through the attenuation of cell cycle progression via AhR-mediated cascade.
Jung
Nak-Kyun
NK
Hormone Research Center and School of Biological Sciences & Technology, Chonnam National University, Kwangju, Republic of Korea.
Park
Jy-Young
JY
Park
Jeong-Hoh
JH
Kim
Sung-Yun
SY
Park
Jin-Ki
JK
Chang
Won-Kyong
WK
Lee
Hwi-Cheul
HC
Kim
Sung-Woo
SW
Chun
Sang-Young
SY
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects*; D056742:Cyclin D2 / Q000235:genetics / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics / Q000378:metabolism; D052244:Endocrine Disruptors / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006107:Granulosa Cells / Q000187:drug effects* / Q000378:metabolism; D006131:Growth Inhibitors / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D010053:Ovary / Q000187:drug effects / Q000254:growth & development; D010062:Ovulation Induction; D034445:Ovulation Inhibition / Q000187:drug effects*; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D012102:Reproductive Control Agents / Q000494:pharmacology; D013997:Time Factors
C486197:Ccnd2 protein, rat; D056742:Cyclin D2; D052244:Endocrine Disruptors; D006131:Growth Inhibitors; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D012102:Reproductive Control Agents; C495892:Cdk2 protein, rat; D051357:Cyclin-Dependent Kinase 2