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枸橼酸他莫昔芬对成年雌性大鼠卵巢卵泡颗粒细胞的影响:光镜研究

The Effect of Tamoxifen Citrate on Granulosa Cells of Ovarian Follicles in Adult Female Rats: Light Microscopic Study.

作者信息

Aljassim Fatimah Khalil, El-Sheikh Amal Ahmed, Motabagani Mohamed A

机构信息

Department of Anatomy, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.

出版信息

J Microsc Ultrastruct. 2022 Nov 9;12(1):1-5. doi: 10.4103/jmau.jmau_79_21. eCollection 2024 Jan-Mar.

DOI:10.4103/jmau.jmau_79_21
PMID:38633571
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11019587/
Abstract

BACKGROUND

Tamoxifen is a drug that has been used extensively as a chemotherapeutic agent for breast cancer. It should be taken for a long period, from few weeks up to many years, so it can induce gynecological and nongynecological complications.

AIM

Present study was conducted to clarify the histopathological effects of tamoxifen intake on the ovarian follicles of rats and evaluate the promising recovery after drug withdrawal.

MATERIALS AND METHODS

Adult female albino rats ( = 24) were randomly divided into four groups. Group I: Control rats without treatment. Group II: Rats received olive oil vehicle. Group III: Rats received 5 mg/kg daily of tamoxifen dissolved in olive oil by oral administration for 4 weeks. Group IV: Rats received tamoxifen as in Group III then will be kept for another 4 weeks without treatment for recovery. Then, the rats were anaesthetized and the ovaries were removed and prepared for histological assessment by light microscope.

RESULTS

The ovarian histological findings in the ovary of Group III revealed an increase in atretic ovarian follicles, appearance of cystic ovarian follicles, and cystic corpus luteum. The granulosa cells of ovarian follicles were disorganized with vacuolation of their cytoplasm, increased number of pyknotic nuclei, fragmented nuclei, and apoptotic bodies. After the withdrawal of drug, the ovarian tissue showed slight improvement with the appearance of some atretic follicles with degenerated oocyte and stromal hyperplasia.

CONCLUSION

Based on the results, tamoxifen induced marked histological changes in the ovary. If tamoxifen is mandatory for the prevention of breast cancer, frequent gynecological examination should be carried out to detect any side effects.

摘要

背景

他莫昔芬是一种被广泛用作乳腺癌化疗药物的药物。它需要长期服用,从几周至数年不等,因此可能引发妇科和非妇科并发症。

目的

进行本研究以阐明服用他莫昔芬对大鼠卵巢卵泡的组织病理学影响,并评估停药后有望出现的恢复情况。

材料与方法

将24只成年雌性白化病大鼠随机分为四组。第一组:未接受治疗的对照大鼠。第二组:接受橄榄油载体的大鼠。第三组:大鼠通过口服给予溶解于橄榄油中的他莫昔芬,剂量为5毫克/千克,持续4周。第四组:大鼠按第三组方式接受他莫昔芬治疗,然后停药4周以观察恢复情况。随后,将大鼠麻醉并摘除卵巢,制备用于光学显微镜组织学评估的样本。

结果

第三组大鼠卵巢的组织学检查结果显示闭锁卵泡增多、出现囊性卵巢卵泡和囊性黄体。卵巢卵泡的颗粒细胞排列紊乱,细胞质有空泡化,固缩核数量增加、核碎片化以及出现凋亡小体。停药后,卵巢组织有轻微改善,出现一些卵母细胞退化的闭锁卵泡和间质增生。

结论

基于这些结果,他莫昔芬可引起卵巢明显的组织学变化。如果预防乳腺癌必须使用他莫昔芬,则应频繁进行妇科检查以检测任何副作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04eb/11019587/aada1f70f925/JMAU-12-1-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04eb/11019587/debf434f7e3e/JMAU-12-1-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04eb/11019587/45d4e128f571/JMAU-12-1-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04eb/11019587/ce4ddbfe0bee/JMAU-12-1-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04eb/11019587/cb930577f75e/JMAU-12-1-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04eb/11019587/46b14470ddfd/JMAU-12-1-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04eb/11019587/aada1f70f925/JMAU-12-1-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04eb/11019587/debf434f7e3e/JMAU-12-1-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04eb/11019587/45d4e128f571/JMAU-12-1-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04eb/11019587/ce4ddbfe0bee/JMAU-12-1-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04eb/11019587/cb930577f75e/JMAU-12-1-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04eb/11019587/46b14470ddfd/JMAU-12-1-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04eb/11019587/aada1f70f925/JMAU-12-1-g006.jpg

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本文引用的文献

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Tamoxifen suppresses brain metastasis of estrogen receptor-deficient breast cancer by skewing microglia polarization and enhancing their immune functions.他莫昔芬通过改变小胶质细胞极化状态并增强其免疫功能抑制雌激素受体阴性乳腺癌脑转移。
Breast Cancer Res. 2021 Mar 18;23(1):35. doi: 10.1186/s13058-021-01412-z.
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Estrogen Receptors in Polycystic Ovary Syndrome.多囊卵巢综合征中的雌激素受体。
Cells. 2021 Feb 21;10(2):459. doi: 10.3390/cells10020459.
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Endocrine Risk Factors of Endometrial Cancer: Polycystic Ovary Syndrome, Oral Contraceptives, Infertility, Tamoxifen.
子宫内膜癌的内分泌危险因素:多囊卵巢综合征、口服避孕药、不孕症、他莫昔芬。
Cancers (Basel). 2020 Jul 2;12(7):1766. doi: 10.3390/cancers12071766.
4
Concurrent tamoxifen-related Müllerian adenofibromas in uterus and ovary.子宫和卵巢同时出现的与他莫昔芬相关的苗勒管腺纤维瘤。
Int J Clin Exp Pathol. 2015 Nov 1;8(11):15381-5. eCollection 2015.
5
Tamoxifen prevents apoptosis and follicle loss from cyclophosphamide in cultured rat ovaries.他莫昔芬可预防环磷酰胺诱导的培养大鼠卵巢细胞凋亡和卵泡丢失。
Biol Reprod. 2015 May;92(5):132. doi: 10.1095/biolreprod.114.126136. Epub 2015 Apr 1.
6
Effect of tamoxifen on ovarian reserve: A randomized controlled assessor-blind trial in a mouse model.他莫昔芬对卵巢储备功能的影响:小鼠模型中的一项随机对照、评估者盲法试验。
J Turk Ger Gynecol Assoc. 2014 Dec 1;15(4):228-32. doi: 10.5152/jtgga.2014.14166. eCollection 2014.
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Nonproliferative and proliferative lesions of the rat and mouse female reproductive system.大鼠和小鼠雌性生殖系统的非增殖性和增殖性病变
J Toxicol Pathol. 2014;27(3-4 Suppl):1S-107S. doi: 10.1293/tox.27.1S.
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Morphological and immunohistochemical analysis in ovaries and fallopian tubes of tamoxifen, letrozole and clomiphene-treated rats.他莫昔芬、来曲唑和氯米酚处理的大鼠卵巢和输卵管的形态学和免疫组织化学分析。
Arch Gynecol Obstet. 2014 Sep;290(3):553-9. doi: 10.1007/s00404-014-3234-4. Epub 2014 Apr 12.
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Tumorigenic effects of tamoxifen on the female genital tract.他莫昔芬对女性生殖道的致瘤作用。
Clin Med Pathol. 2008;1:17-34. doi: 10.4137/cpath.s487. Epub 2008 Mar 1.
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Tamoxifen decreases ovarian follicular loss from experimental toxicant DMBA and chemotherapy agents cyclophosphamide and doxorubicin in the rat.他莫昔芬可减少 DMBA 实验性毒物和环磷酰胺及阿霉素化疗药物引起的大鼠卵巢卵泡丢失。
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