title: Attenuation of cell cycle progression by 2,3,7,8-tetrachlorodibenzo-p-dioxin eliciting ovulatory blockade in gonadotropin-primed immature rats.
abstract: 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.
authors: Hormone Research Center and School of Biological Sciences & Technology, Chonnam National University, Kwangju, Republic of Korea.
authors: Nak-Kyun
authors: NK
authors: Jung
authors: Jy-Young
authors: JY
authors: Park
authors: Jeong-Hoh
authors: JH
authors: Park
authors: Sung-Yun
authors: SY
authors: Kim
authors: Jin-Ki
authors: JK
authors: Park
authors: Won-Kyong
authors: WK
authors: Chang
authors: Hwi-Cheul
authors: HC
authors: Lee
authors: Sung-Woo
authors: SW
authors: Kim
authors: Sang-Young
authors: SY
authors: Chun
mesh_terms: 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
chemical_list: 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