Novel ovarian endometriosis model causes infertility via iron-mediated oxidative stress in mice.
Novel ovarian endometriosis model causes infertility via iron-mediated oxidative stress in mice.
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DOI：
10.1016/j.redox.2020.101726
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发表时间：
2020-10
期刊：
影响因子：
11.4
通讯作者：
Toyokuni S
中科院分区：
文献类型：
--
作者：
Hayashi S;Nakamura T;Motooka Y;Ito F;Jiang L;Akatsuka S;Iwase A;Kajiyama H;Kikkawa F;Toyokuni S
卵巢子宫内膜异位症（OE）不仅给育龄妇女带来严重的月经疼痛，而且还导致不孕和卵巢癌发生的风险增加。虽然腹膜子宫内膜异位症模型已经开发了同基因植入切碎的子宫组织和致癌K-ras等位基因与条件Pten删除卵巢表面上皮内产生癌前子宫内膜腺体形态，其次是卵巢样腺癌，一直没有类似于人类同行的OE小鼠模型，适用于临床前研究。在这里，我们首次建立了一个小鼠OE模型，揭示不孕症，并评估参与铁催化氧化应激的发病机制。将雌性小鼠的子宫组织块植入同系小鼠卵巢表面诱发卵巢上皮性变（OE），植入后4周，85.7%（12/14）的小鼠子宫内膜异位生长。子宫内膜异位症病变累及肠、胰腺和腹膜壁。OE组中卵巢周围纤维化明显，并呈时间依赖性增加。OE组铁积累显著增加，导致卵泡各阶段的氧化应激，通过4-羟基-2-壬烯醛修饰蛋白和8-羟基-2 ′-脱氧鸟苷评估。促卵泡激素受体在卵泡中的表达在OE组的窦前、窦期和排卵前期均显著降低。最后，与对照组相比，OE组的幼仔数量显著减少。这个模型提供了一个机会，以评估药物或程序，以抵消卵巢子宫内膜异位症在临床前设置。本研究首次建立了一种经粘液囊切除的小鼠卵巢子宫内膜异位症模型。卵巢子宫内膜异位症诱导卵泡铁催化氧化应激。卵巢子宫内膜异位症模型揭示了不孕症，适用于临床前研究。
Ovarian endometriosis (OE) provides women of reproductive age with not only severe menstrual pain but also infertility and an increased risk for ovarian carcinogenesis. Whereas peritoneal endometriosis models have been developed with syngeneic implantation of minced uterine tissue and oncogenic K-ras allele with conditional Pten deletion within ovarian surface epithelium generated preneoplastic endometrial glandular morphology, followed by endometrioid adenocarcinoma, there has been no mouse model of OE similar to human counterparts, applicable to preclinical studies. Here we for the first time established a murine OE model that reveals infertility, and evaluated the involvement of iron catalyzed oxidative stress in the pathogenesis. Minced uterine tissue from female mice was implanted on ovarian surface of syngeneic mice after bursectomy to induce OE. Ectopic growth of endometrium was observed in association with ovary 4 weeks after implantation in 85.7% (12/14) of the operated mice with our protocol. Endometriotic lesions involved intestine, pancreas and peritoneal wall. Fibrosis around the ovary was prominent and increased time-dependently in the OE group. Iron accumulation was significantly increased in the OE group, leading to oxidative stress in each stage of the follicles as evaluated by 4-hydroxy-2-nonenal-modified proteins and 8-hydroxy-2′-deoxyguanosine. Expression of follicle stimulating hormone receptor in the follicles revealed a significant decrease during pre-antral, antral and pre-ovulatory phases in the OE group. Finally, the number of pups was significantly reduced in the OE group in comparison to the controls. This model affords an opportunity to evaluate agents or procedures to counteract ovarian endometriosis in the preclinical settings. We for the first time established a murine ovarian endometriosis model via bursectomy. Ovarian endometriosis induced iron catalyzed oxidative stress in ovarian follicles. This ovarian endometriosis model reveals infertility and is applicable to preclinical studies.
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影响因子：
3.2
作者：
Macer ML;Taylor HS
通讯作者：
Taylor HS
DOI：
10.1186/s12958-018-0426-y
发表时间：
2018-10-27
期刊：
Reproductive biology and endocrinology : RB&E
影响因子：
--
作者：
Qin Y;Iwase A;Murase T;Bayasula;Ishida C;Kato N;Nakamura T;Osuka S;Takikawa S;Goto M;Kotani T;Kikkawa F
通讯作者：
Kikkawa F
影响因子：
82.9
作者：
Dinulescu, DM;Ince, TA;Jacks, T
通讯作者：
Jacks, T
颗粒卵丘细胞过度氧化应激诱导细胞衰老导致子宫内膜异位症相关不孕
影响因子：
11.4
作者：
Lin, Xiang;Dai, Yongdong;Zhang, Songying
通讯作者：
Zhang, Songying
影响因子：
3.7
作者：
Bilotas MA;Olivares CN;Ricci AG;Baston JI;Bengochea TS;Meresman GF;Barañao RI
通讯作者：
Barañao RI