Exogenous insulin-like growth factor 1 accelerates growth and maturation of follicles in human cortical xenografts and increases ovarian output in mice.
Exogenous insulin-like growth factor 1 accelerates growth and maturation of follicles in human cortical xenografts and increases ovarian output in mice.
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DOI：
10.1016/j.xfss.2021.07.002
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发表时间：
2021-08
期刊：
影响因子：
--
通讯作者：
James, Daylon
中科院分区：
文献类型：
--
作者：
Man, Limor;Lustgarten Guahmich, Nicole;Kallinos, Eleni;Park, Laura;Caiazza, Barbara;Khan, Monica;Liu, Zong-Ying;Patel, Ritaben;Torres, Carmen;Lekovich, Jovana;Zhong, Liangwen;Bodine, Richard;Wen, Duancheng;Zaninovic, Nikica;Schattman, Glenn;Rosenwaks, Zev;James, Daylon
测定外源性胰岛素样生长因子 1 (IGF1) 对人卵巢皮质异种移植物中卵泡生长和成熟的影响。异种移植模型。大学研究实验室。卵巢组织是在脑死亡器官捐献者或接受卵巢组织冷冻保存以保存生育能力的患者同意和机构审查委员会批准的情况下捐献的。将皮质碎片移植到免疫功能低下的小鼠体内。来自四名女性（年龄分别为 19、25、33 和 46 岁）的冷冻保存的卵巢皮质碎片被移植到免疫功能低下小鼠的臀肌中，该小鼠的臀肌中含有内皮细胞的纤维蛋白基质，这些内皮细胞被编码分泌型 IGF1 的慢病毒颗粒转导。异种移植物在 3、8 和 14 周后恢复。此外，对C57/Bl6小鼠进行卵巢内注射盐水或重组IGF1（60μg），然后进行超排卵、乙炔基脱氧尿苷掺入分析以及整个卵巢的核糖核酸测序。对于异种移植：卵泡计数和分布；窦卵泡计数；和黄体/白色念珠菌计数。对于小鼠：卵泡计数和分布；卵母细胞产量、乙炔脱氧尿苷掺入（颗粒细胞增殖）；和卵巢转录组特征。 3周时，IGF1条件下的异种移植物显示初级卵泡的百分比下降，而集中在窦前亚型的次级卵泡的百分比增加； 8周时，次级卵泡的增加集中在简单亚型； 14周后，原始卵泡减少，虽然高级卵泡的数量并没有使实验证明其意义，但窦卵泡减少，黄体增加。小鼠的支持实验显示，卵巢内注射重组 IGF1（60 μg）后，正常卵母细胞数量增加，并且二级和腔前阶段卵泡的增殖指数增加。注射重组 IGF1 (25 μg) 后对整个卵巢进行的核糖核酸测序分析显示，与类固醇生成和黄体化相关的转录物急剧（24 小时）上调。外源性 IGF1 加快了原始、初级和次级卵泡的生长速度，但导致长期（14 周）异种移植物中窦期卵泡几乎不存在。在小鼠中，急性注射 IGF1 可促进卵泡提前并增加卵母细胞产量。结果表明，虽然超生理IGF1单独促进早期/窦前卵泡的生长速度，但持续和/或后期的影响会破坏窦卵泡的生长/存活或促进过早黄体化。这些发现为解释卵泡生长/动员提供了一个时间框架，并且可能有助于理解人类生长激素在辅助生殖中的临床应用。
To measure the influence of exogenous insulin-like growth factor 1 (IGF1) on follicle growth and maturation in human ovarian cortical xenografts. Xenotransplantation model. University-based research laboratory. Ovarian tissue was donated with consent and institutional review board approval by brain-dead organ donors or patients undergoing ovarian tissue cryopreservation for fertility preservation. Cortical fragments were transplanted into immunocompromised mice. Cryopreserved ovarian cortical fragments from four women (aged 19, 25, 33, and 46 years) were transplanted into the gluteus muscle of immunocompromised mice in a fibrin matrix containing endothelial cells that were transduced with lentiviral particles encoding secreted IGF1. Xenografts were recovered after 3, 8, and 14 weeks. In addition, C57/Bl6 mice underwent intraovarian injection of saline or recombinant IGF1 (60 μg), followed by superovulation, analysis of ethynyl-deoxyuridine incorporation, and ribonucleic acid sequencing of the whole ovaries. For xenografts: follicle count and distribution; antral follicle count; and corpora lutea/albicans count. For mice: follicle count and distribution; oocyte yield, ethynyl-deoxyuridine incorporation (granulosa cell proliferation); and ovarian transcriptomic signature. At 3 weeks, xenografts in the IGF1 condition revealed a decreased percentage of primary follicles and increased percentage of secondary follicles that were concentrated in the preantral subtype; at 8 weeks, an increase in secondary follicles was concentrated in the simple subtype; after 14 weeks, primordial follicles were reduced, and while the number of advanced follicles did not power the experiment to demonstrate significance, antral follicles reduced and corpora lutea increased. Supporting experiments in mice revealed an increase in normal oocytes following intraovarian injection of recombinant IGF1 (60 μg) as well as increased proliferative index among follicles of secondary and preantral stages. Ribonucleic acid sequencing analysis of the whole ovaries following injection of recombinant IGF1 (25 μg) revealed an acute (24 hours) upregulation of transcripts related to steroidogenesis and luteinization. Exogenous IGF1 advances the pace of growth among primordial, primary, and secondary stage follicles but results in near absence of antral stage follicles in long-term (14 weeks) xenografts. In mice, acute administration of IGF1 promotes follicle advance and increased oocyte yield. The results suggest that while superphysiological IGF1 alone advances the pace of growth among early/preantral follicles, a sustained and/or later-stage influence undermines antral follicle growth/survival or promotes premature luteinization. These findings provide a temporal framework for interpreting follicle growth/mobilization and may be useful in understanding the clinical application of human growth hormone in the context of assisted reproduction.
影响因子：
2.4
作者：
Hanaue M;Miwa N;Takamatsu K
通讯作者：
Takamatsu K