Impact of obesity on 7,12-dimethylbenz[a]anthracene-induced altered ovarian connexin gap junction proteins in female mice.
Impact of obesity on 7,12-dimethylbenz[a]anthracene-induced altered ovarian connexin gap junction proteins in female mice.
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DOI：
10.1016/j.taap.2014.10.020
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发表时间：
2015-01-01
影响因子：
3.8
通讯作者：
Keating AF
中科院分区：
文献类型：
--
作者：
Ganesan S;Nteeba J;Keating AF
卵巢间隙连接蛋白α 4（GJA 4或连接蛋白37; CX 37）、α 1（GJA 1或连接蛋白43; CX 43）和γ 1（GJC 1或连接蛋白45; CX 45）参与细胞通讯和卵泡发生。7，12-二甲基苯并[a]蒽（DMBA）改变培养的新生大鼠卵巢中Cx 37和Cx43的表达。此外，肥胖对DMBA诱导的卵巢细胞死亡和卵泡耗竭具有累加效应，因此，我们研究了肥胖和DMBA对CX蛋白水平的体内影响。从6、12、18或24周龄的瘦小鼠和肥胖小鼠收集卵巢。对18周龄小鼠（瘦小鼠和肥胖小鼠）的子集给予芝麻油或DMBA（1 mg/kg; ip）14天，并在此后3天收集卵巢。18周时，肥胖大鼠卵巢Cx43、Cx45 mRNA和蛋白水平均下降（P < 0.05）; 24周时，肥胖大鼠卵巢Cx 37 mRNA和蛋白水平下降（P < 0.05）。DMBA暴露后，肥胖大鼠卵巢中Cx 37 mRNA和窦卵泡蛋白表达强度降低（P < 0.05），Cx 37蛋白总量降低（P < 0.05）。DMBA处理使瘦型和肥胖型卵巢Cx43 mRNA和总蛋白水平降低（P < 0.05），而肥胖对照组的基础蛋白染色强度降低（P < 0.05）。肥胖组Cx45 mRNA、总蛋白及蛋白质染色强度均降低（P < 0.05）。这些数据支持，肥胖暂时改变间隙连接蛋白的表达，DMBA诱导的卵毒性可能涉及减少间隙连接蛋白的功能。
The ovarian gap junction proteins alpha 4 (GJA4 or connexin 37; CX37), alpha 1 (GJA1 or connexin 43; CX43) and gamma 1 (GJC1 or connexin 45; CX45) are involved in cell communication and folliculogenesis. 7,12-dimethylbenz[a]anthracene (DMBA) alters Cx37 and Cx43 expression in cultured neonatal rat ovaries. Additionally, obesity has an additive effect on DMBA-induced ovarian cell death and follicle depletion, thus, we investigated in vivo impacts of obesity and DMBA on CX protein levels. Ovaries were collected from lean and obese mice aged 6, 12, 18, or 24 wks. A subset of 18 wk old mice (lean and obese) were dosed with sesame oil or DMBA (1mg/kg; ip) for 14 days and ovaries collected 3 days thereafter. Cx43 and Cx45 mRNA and protein levels decreased (P < 0.05) after 18 wks while Cx37 mRNA and protein levels decreased (P < 0.05) after 24 wks in obese ovaries. Cx37 mRNA and antral follicle protein staining intensity were reduced (P < 0.05) by obesity while total CX37 protein was reduced (P < 0.05) in DMBA exposed obese ovaries. Cx43 mRNA and total protein levels were decreased (P < 0.05) by DMBA in both lean and obese ovaries while basal protein staining intensity was reduced (P < 0.05) in obese controls. Cx45 mRNA, total protein and protein staining intensity level were decreased (P < 0.05) by obesity. These data support that obesity temporally alters gap junction protein expression and that DMBA-induced ovotoxicity may involve reduced gap junction protein function.