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

ABSTRACT: Busulfan 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.

SUBMITTER: Jing J

PROVIDER: S-EPMC10849791 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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

Jing Jun J Ouyang Lei L Zhang Hong H Liang Kuan K Ma Rujun R Ge Xie X Tang Ting T Zhao Shanmeizi S Xue Tongmin T Shen Jiaming J Ma Jinzhao J Li Zhou Z Wu Jing J Yang Yang Y Zhao Wei W Zheng Lu L Qian Zhang Z Sun Shanshan S Ge Yifeng Y Chen Li L Li Chaojun C Yao Bing B

Cell proliferation 20230924 2

Busulfan 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 ...[more]

PMID: 37743695

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Project description:We examined if the distribution of impaired or normal spermatogenesis differs along the length of seminiferous tubules in disorders of spermatogenesis. For this purpose, three-dimensional (3D) reconstruction of seminiferous tubules was performed in mice with experimental spermatogenesis disorder induced by intraperitoneal injection of busulfan, and the areas of impaired and normal spermatogenesis were analyzed microscopically. The volume of the testis and length of seminiferous tubules decreased, and the proportion of tubule areas with impaired spermatogenesis increased depending on the dose of busulfan. With the highest dose of busulfan, although the proportion of impaired spermatogenesis was similar among individual seminiferous tubules, it was slightly but significantly higher in shorter tubules and in tubule areas near branching points. The tubule areas with impaired and normal spermatogenesis consisted of many segments of varying lengths. With increasing doses of busulfan, the markedly impaired segments increased in length without changing in number, whereas normal segments, although reduced in number and length, remained even with the highest dose of busulfan. Individual remaining normal segments consisted of several different stages, among which stage I and XII were found at higher frequencies, and stage VI at a lower frequency than expected in normal seminiferous tubules. We also examined if the distribution of impaired or normal spermatogenesis differs among different 3D positions in the testis without considering the course of seminiferous tubules. Although the proportions of impaired spermatogenesis with the minimum dose of busulfan and normal spermatogenesis with the highest dose of busulfan greatly varied by location within a single testis, there were no 3D positions with these specific proportions common to different testes, suggesting that the factors influencing the severity of busulfan-induced spermatogenesis disorder are not fixed in location among individual mice.

Dataset Information

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

Publications

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

Similar Datasets

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