Omega‐3 polyunsaturated fatty acids and its metabolite 12‐HEPE rescue busulfan disrupted spermatogenesis via target to GPR120

Author:

Jing Jun123ORCID,Ouyang Lei4,Zhang Hong3,Liang Kuan24,Ma Rujun23,Ge Xie23,Tang Ting123,Zhao Shanmeizi5ORCID,Xue Tongmin126,Shen Jiaming3,Ma Jinzhao23ORCID,Li Zhou3,Wu Jing7,Yang Yang8,Zhao Wei23,Zheng Lu3,Qian Zhang3,Sun Shanshan5,Ge Yifeng23,Chen Li23,Li Chaojun1,Yao Bing12345ORCID

Affiliation:

1. State Key Laboratory of Reproductive Medicine and Offspring Health Nanjing Medical University Nanjing China

2. Department of Reproductive Medicine, Affiliated Jinling Hospital Nanjing Medical University Nanjing China

3. Department of Reproductive Medicine, Affiliated Jinling Hospital, Clinical School of Medical College Nanjing University Nanjing China

4. Department of Reproductive Medicine, Affiliated Jinling Hospital, The First School of Clinical Medicine Southern Medical University Nanjing China

5. School of Life Science Nanjing Normal University Nanjing China

6. Reproductive Medical Center, Clinical Medical College (Northern Jiangsu People's Hospital) Yangzhou University Yangzhou China

7. Core Laboratory, Sir Run Run Hospital Nanjing Medical University Nanjing China

8. Basic Medical Laboratory, Affiliated Jinling Hospital, Clinical School of Medical College Nanjing University Nanjing China

Abstract

AbstractBusulfan is an antineoplastic, which is always accompanied with the abnormal of spermatogonia self‐renewal and differentiation. It has been demonstrated that the omega‐3 polyunsaturated fatty acids (PUFAs) benefits mature spermatozoa. However, whether omega‐3 can protect endogenous spermatogonia and the detailed mechanisms are still unclear. Evaluate of spermatogenesis function (in vivo) were examined by histopathological analysis, immunofluorescence staining, and western blotting. The levels of lipid metabolites in testicular tissue were determined via liquid chromatography. We investigated the effect of lipid metabolites on Sertoli cells provided paracrine factors to regulate spermatogonia proliferation and differentiation using co‐culture system. In our study, we showed that omega‐3 PUFAs significantly improved the process of sperm production and elevated the quantity of both undifferentiated Lin28+ spermatogonia and differentiated c‐kit+ spermatogonia in a mouse model where spermatogenic function was disrupted by busulfan. Mass spectrometry revealed an increase in the levels of several omega‐3 metabolites in the testes of mice fed with omega‐3 PUFAs. The eicosapentaenoic acid metabolite 12‐hydroxyeicosapentaenoic acid (12‐HEPE) up‐regulated bone morphogenic protein 4 (BMP4) expression through GPR120‐ERK1/2 pathway activation in Sertoli cells and restored spermatogonia proliferation and differentiation. Our study provides evidence that omega‐3 PUFAs metabolite 12‐HEPE effectively protects spermatogonia and reveals that GPR120 might be a tractable pharmacological target for fertility in men received chemotherapy or severe spermatogenesis dysfunction.

Funder

National Key Research and Development Program of China

National Natural Science Foundation of China

Publisher

Wiley

Subject

Cell Biology,General Medicine

Reference77 articles.

1. Recipient preparation is critical for spermatogonial transplantation in the rat

2. The effects of olive leaf extract on the testis, sperm quality and testicular germ cell apoptosis in male rats exposed to busulfan;Ganjalikhan Hakemi S;Int J Fertil Steril,2019

3. Toxicological review of busulfan (Myleran)

4. The roles and mechanisms of Leydig cells and myoid cells in regulating spermatogenesis

5. The spermatogonial stem cell niche

Cited by 3 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3