Impact of obesity on ovotoxicity induced by 7,12-dimethylbenz[a]anthracene in mice.
Impact of obesity on ovotoxicity induced by 7,12-dimethylbenz[a]anthracene in mice.
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肥胖对 7,12-二甲基苯并[a]蒽诱导的小鼠卵毒性的影响。
DOI：
10.1095/biolreprod.113.114215
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发表时间：
2014
影响因子：
3.6
通讯作者：
Keating,AileenF
中科院分区：
文献类型：
--
作者：
Nteeba,Jackson;Ganesan,Shanthi;Keating,AileenF
胰岛素在肥胖期间升高，可能通过磷脂酰肌醇3-激酶(PI3K)信号调节卵巢外组织中的外源生物转化酶。PI3K调节卵母细胞活力、卵泡激活和卵巢化学生物转化。7，12-二甲基苯并[a]蒽(DMBA)是一种致癌物和卵毒物质，会破坏卵泡的各个阶段，导致卵巢早衰。据报道，肥胖会促进DMBA诱导的肿瘤，但肥胖是否会影响卵巢的异种代谢仍不清楚。因此，我们研究了DMBA暴露(1 mg/kg，腹腔注射14天)后，异源代谢基因微粒体环氧化物水解酶(Ephx1)、谷胱甘肽转移酶(GST)类PI(GSTP1)和类MU1(GSTM1)以及PI3K信号成员(蛋白激酶B[AKT]α[Akt1]、β[Akt2]和叉头转录因子亚家族3[Foxo3])在瘦体和肥胖雌性小鼠卵巢中的表达。相对于瘦小鼠，肥胖小鼠健康的原始和初级卵泡数量减少(P<；0.05)，次级和排卵前卵泡数量增加(P<；0.05)。肥胖增加(P<；0.05)Akt1、Akt2、GSTM1和Ephx1mRNA以及pAKTSer473/Thr308、GSTM1、GSTP1和EPHX1蛋白水平。DMBA降低了瘦小鼠和肥胖小鼠的卵巢重量(P<；0.05)，然而，肥胖DMBA处理的雌性小鼠卵巢重量的下降幅度更大(P<；0.05)。在瘦小和肥胖小鼠中，DMBA均减少(P<；0.05)健康卵泡数量，增加Gstp1和Ephx1mRNA以及GSTM1、GSTP1和EPHX1蛋白水平，降低Akt1和Akt2mRNA以及pAKTSer473或pAKTThr308、FOX03和pFOXO3Ser253蛋白的表达。肥胖与DMBA暴露对Gstm1和Ephx1mRNA以及GSTM1和EPHX1蛋白表达的增加存在相加效应。
Insulin, elevated during obesity, regulates xenobiotic biotransformation enzymes, potentially through phosphatidylinositol 3-kinase (PI3K) signaling, in extraovarian tissues. PI3K regulates oocyte viability, follicular activation, and ovarian chemical biotransformation. 7,12-Dimethylbenz[a]anthracene (DMBA), a carcinogen and ovotoxicant, destroys all stages of follicles, leading to premature ovarian failure. Obesity has been reported to promote DMBA-induced tumors, but it remains unknown whether obesity affects ovarian xenobiotic metabolism. Therefore, we investigated ovarian expression of xenobiotic metabolism genes—microsomal epoxide hydrolase (Ephx1), glutathioneS-transferase (GST) class Pi (Gstp1) and class mu 1 (Gstm1), and PI3K-signaling members (protein kinase B [AKT] alpha [Akt1], beta [Akt2], and the forkhead transcription factor subfamily 3 [Foxo3])—in lean and obese female mice after DMBA exposure (1 mg/kg; intraperitoneal injection for 14 days). Relative to lean, obese mice had decreased (P< 0.05) healthy primordial and primary follicle numbers but increased (P< 0.05) secondary and preovulatory follicles numbers. Obesity increased (P< 0.05)Akt1, Akt2, Gstm1,andEphx1mRNA and pAKTSer473/Thr308, GSTM1, GSTP1, and EPHX1 protein levels. DMBA decreased (P< 0.05) ovarian weight in lean and obese mice, however, obese DMBA-treated females had a greater reduction (P< 0.05) in ovarian weight. In both lean and obese mice, DMBA decreased (P< 0.05) all stages of healthy follicle numbers, increasedGstp1andEphx1mRNA as well as GSTM1, GSTP1, and EPHX1 protein levels, and decreasedAkt1andAkt2mRNA as well as pAKTSer473or pAKTThr308, FOXO3, and pFOXO3Ser253protein expression. There was an additive effect between obesity and DMBA exposure for increasedGstm1andEphx1mRNA as well as GSTM1 and EPHX1 protein expression.
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通过先证者确定的家庭中方差分量模型的稳健推断：I. 先证者表型的调节
影响因子：
2.1
作者：
T. Beaty;K. Liang;D. Rao
通讯作者：
D. Rao
通过复杂分离分析检测家系间的遗传异质性：在高胆固醇血症中的应用。
影响因子：
9.8
作者：
P. Moll;T. Berry;W. Weidman;R. Ellefson;H. Gordon;B. Kottke
通讯作者：
B. Kottke
通过截断确定的家庭数据的多因素分析：两种统计推断方法的比较评估。
影响因子：
9.8
作者：
Rao,DC;Wette,R;Ewens,WJ
通讯作者：
Ewens,WJ
精神分裂症：遗传模型的系统构建。
影响因子：
9.8
作者：
J. Stewart
通讯作者：
J. Stewart
谱系数据方差分量模型的确定和拟合优度。
DOI：
--
发表时间：
1984
期刊：
Progress in clinical and biological research
影响因子：
--
作者：
M. Boehnke;K. Lange
通讯作者：
K. Lange