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卵巢支架促进了环磷酰胺损伤小鼠卵巢的恢复。

Ovarian scaffolds promoted mouse ovary recovery from cyclophosphamide damage.

机构信息

College of Biological Sciences, Inner Mongolia University, 235 West Univ. Road, Hohhot, 010021, Inner Mongolia, China.

Key Laboratory of Medical Cell Biology, Clinical Medicine Research Center, Affiliated Hospital of Inner Mongolia Medical University, 1 Tongdao North Street, Hohhot, 010050, Inner Mongolia, China.

出版信息

J Reprod Immunol. 2023 Jun;157:103950. doi: 10.1016/j.jri.2023.103950. Epub 2023 Apr 13.

DOI:10.1016/j.jri.2023.103950
PMID:37079974
Abstract

There is growing evidence to suggest that scaffold of tissue can promote the tissue reparation. In this study, we investigate the effects of ovarian scaffolds on the reparation of cyclophosphamide (CPA) damaged mice ovaries. The mice were first administered with CPA, was then either transplanted an ovarian scaffold into each ovarian bursa for the experimental group (EG) or underwent sham surgery as the control (CG). To evaluate the extent of ovarian damage caused by CPA, a third group which did not undergo any treatment was included for the normal control (NG). Their ovaries were harvested for examination at day 30, 60, and 90 post CPA injection. We found that in EG, the number of all types of follicles in the ovaries remained almost the same throughout. The numbers of follicles were not significantly different from CG, except at day 60, where in CG the numbers of each type of follicle decreased to basal levels. The decrease in the number of ovarian follicles at day 60 in CG was mirrored by the significant increase in the number of apoptotic granulosa cells in the follicles, and was corroborated further by the basal levels of serum estradiol. Furthermore, we observed a significant decrease in collagen composition preceded by macrophage polarization, and elevation of inflammatory cytokine expression in the ovaries of the EG compared to the CG at day 60. We concluded that ovarian scaffolds can effectively protect primordial follicles from CPA-damage and promote the reparation of CPA-damaged ovaries. This research establishes a proof of concept for the future treatment of chemo-damaged ovaries.

摘要

越来越多的证据表明,组织支架可以促进组织修复。在这项研究中,我们研究了卵巢支架对环磷酰胺(CPA)损伤的小鼠卵巢修复的影响。首先给小鼠注射 CPA,实验组(EG)将卵巢支架移植到每个卵巢囊,对照组(CG)则进行假手术。为了评估 CPA 对卵巢造成的损伤程度,我们还设立了未接受任何治疗的正常对照组(NG)。在 CPA 注射后第 30、60 和 90 天,采集它们的卵巢进行检查。我们发现,在 EG 中,卵巢中所有类型的卵泡数量在整个过程中几乎保持不变。除了第 60 天,CG 中每个类型的卵泡数量减少到基础水平外,卵泡数量与 CG 无显著差异。CG 中卵泡数量在第 60 天的减少与卵泡中颗粒细胞凋亡数量的显著增加相吻合,血清雌二醇水平也进一步证实了这一点。此外,我们还观察到,与 CG 相比,EG 中卵巢内胶原组成的显著减少伴随着巨噬细胞极化的增加,以及炎症细胞因子表达的升高,这一现象在第 60 天尤为明显。我们得出结论,卵巢支架可以有效地保护原始卵泡免受 CPA 损伤,并促进 CPA 损伤的卵巢修复。这项研究为未来化疗损伤卵巢的治疗提供了概念验证。

相似文献

1
Ovarian scaffolds promoted mouse ovary recovery from cyclophosphamide damage.卵巢支架促进了环磷酰胺损伤小鼠卵巢的恢复。
J Reprod Immunol. 2023 Jun;157:103950. doi: 10.1016/j.jri.2023.103950. Epub 2023 Apr 13.
2
Reproductive toxicity of cyclophosphamide in the C57BL/6N mouse: 1. Effects on ovarian structure and function.环磷酰胺对C57BL/6N小鼠的生殖毒性:1. 对卵巢结构和功能的影响。
Reprod Toxicol. 1992;6(5):411-21. doi: 10.1016/0890-6238(92)90004-d.
3
Ceramide-1-phosphate has protective properties against cyclophosphamide-induced ovarian damage in a mice model of premature ovarian failure.神经酰胺-1-磷酸对环磷酰胺诱导的早发性卵巢衰竭小鼠模型中的卵巢损伤具有保护作用。
Hum Reprod. 2018 May 1;33(5):844-859. doi: 10.1093/humrep/dey045.
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The magnitude of gonadotoxicity of chemotherapy drugs on ovarian follicles and granulosa cells varies depending upon the category of the drugs and the type of granulosa cells.化疗药物对卵巢卵泡和颗粒细胞的性腺毒性程度因药物类别和颗粒细胞类型而异。
Hum Reprod. 2015 Dec;30(12):2926-35. doi: 10.1093/humrep/dev256. Epub 2015 Oct 13.
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Both in vivo FSH depletion and follicular exposure to Gonadotrophin-releasing hormone analogues in vitro are not effective to prevent follicular depletion during chemotherapy in mice.体内 FSH 耗竭和体外卵泡暴露于促性腺激素释放激素类似物均不能有效预防化疗小鼠卵泡耗竭。
Mol Hum Reprod. 2018 Apr 1;24(4):221-232. doi: 10.1093/molehr/gay005.
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Dual suppression of follicle activation pathways completely prevents the cyclophosphamide-induced loss of ovarian reserve.双重抑制卵泡激活途径可完全防止环磷酰胺诱导的卵巢储备损失。
Hum Reprod. 2023 Jun 1;38(6):1086-1098. doi: 10.1093/humrep/dead064.
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Inhibitors of apoptosis protect the ovarian reserve from cyclophosphamide.凋亡抑制剂可保护卵巢储备免受环磷酰胺的影响。
J Endocrinol. 2019 Feb 1;240(2):243-256. doi: 10.1530/JOE-18-0370.
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Cisplatin- and cyclophosphamide-induced primordial follicle depletion is caused by direct damage to oocytes.顺铂和环磷酰胺诱导的原始卵泡耗竭是由卵母细胞的直接损伤引起的。
Mol Hum Reprod. 2019 Aug 1;25(8):433-444. doi: 10.1093/molehr/gaz020.
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Effects of cyclophosphamide and buthionine sulfoximine on ovarian glutathione and apoptosis.环磷酰胺和丁硫氨酸亚砜胺对卵巢谷胱甘肽及细胞凋亡的影响。
Free Radic Biol Med. 2004 Jun 1;36(11):1366-77. doi: 10.1016/j.freeradbiomed.2004.02.067.
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Anti-Müllerian hormone inhibits activation and growth of bovine ovarian follicles in vitro and is localized to growing follicles.抗苗勒管激素在体外抑制牛卵巢卵泡的激活和生长,并定位于生长卵泡。
Mol Hum Reprod. 2017 May 1;23(5):282-291. doi: 10.1093/molehr/gax010.

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