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

Jing, Jun; Ouyang, Lei; Zhang, Hong; Liang, Kuan; Ma, Rujun; Ge, Xie; Tang, Ting; Zhao, Shanmeizi; Xue, Tongmin; Shen, Jiaming; Ma, Jinzhao; Li, Zhou; Wu, Jing; Yang, Yang; Zhao, Wei; Zheng, Lu; Qian, Zhang; Sun, Shanshan; Ge, Yifeng; Chen, Li; Li, Chaojun; Yao, Bing

doi:10.1111/cpr.13551

Cited by 3 publications

(1 citation statement)

References 77 publications

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“…However, low level of T and high level of ROS are commonly observed. It has been reported that BUS administration could significantly increase ROS in spermatogonia and inhibit its differentiation and proliferation ( Jing et al, 2023 ). ROS is a double-edged sword in spermatogenesis, high level of ROS could lead to oxidative stress and cell death.…”

Section: Discussionmentioning

confidence: 99%

Ursolic acid attenuates oligospermia in busulfan-induced mice by promoting motor proteins

Dong,

Ye,

Dong

et al. 2024

PeerJ

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Background Oligospermia is one of the most common reasons for male infertility which is troubling numerous couples of child-bearing age. This investigation scrutinizes the implications and mechanistic underpinnings of ursolic acid’s effect on busulfan-induced oligospermia in mouse models. Methods A singular intraperitoneal injection of busulfan at a dosage of 30 mg/kg induced oligospermia. Two weeks subsequent to this induction, mice were subjected to various dosages of ursolic acid (10, 30, and 50 mg/kg body weight, respectively) on a daily basis for four consecutive weeks. Following this treatment period, a meticulous analysis of epididymal sperm parameters, encompassing concentration and motility, was conducted using a computer-assisted sperm analysis system. The histopathology of the mice testes was performed utilizing hematoxylin and eosin staining, and the cytoskeleton regeneration of the testicular tissues was analyzed via immunofluorescent staining. Serum hormone levels, including testosterone, luteinizing hormone, and follicle-stimulating hormone, as well as reactive oxygen species levels (inclusive of reactive oxygen species and malondialdehyde), were gauged employing specific enzyme-linked immunosorbent assay kits. Differentially expressed genes of testicular mRNA between the oligospermia-induced group and the various ursolic acid treatment groups were identified through RNA sequencing analysis. Results The results revealed that a dosage of 50 mg/kg ursolic acid treatment could increase the concentration of epididymal sperm in oligospermia mice, promote the recovery of testicular morphology, regulate hormone levels and ameliorate oxidative damage. The mechanism research results indicated that ursolic acid increased the expression level of genes related to motor proteins in oligospermia mice.

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Section: Discussionmentioning

confidence: 99%

Ursolic acid attenuates oligospermia in busulfan-induced mice by promoting motor proteins

Dong,

Ye,

Dong

et al. 2024

PeerJ

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Octanoic acid mitigates busulfan-induced blood-testis barrier damage by alleviating oxidative stress and autophagy

Cao,

Zhang,

et al. 2024

Lipids Health Dis

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Background The management of male infertility continues to encounter an array of challenges and constraints, necessitating an in-depth exploration of novel therapeutic targets to enhance its efficacy. As an eight-carbon medium-chain fatty acid, octanoic acid (OCA) shows promise for improving health, yet its impact on spermatogenesis remains inadequately researched. Methods Mass spectrometry was performed to determine the fatty acid content and screen for a pivotal lipid component in the serum of patients with severe spermatogenesis disorders. The sperm quality was examined, and histopathological analysis and biotin tracer tests were performed to assess spermatogenesis function and the integrity of the blood-testis barrier (BTB) in vivo. Cell-based in vitro experiments were carried out to investigate the effects of OCA administration on Sertoli cell dysfunction. This research aimed to elucidate the mechanism by which OCA may influence the function of Sertoli cells. Results A pronounced reduction in OCA content was observed in the serum of patients with severe spermatogenesis disorders, indicating that OCA deficiency is related to spermatogenic disorders. The protective effect of OCA on reproduction was tested in a mouse model of spermatogenic disorder induced by busulfan at a dose 30 mg/kg body weight (BW). The mice in the study were separated into distinct groups and administered varying amounts of OCA, specifically at doses of 32, 64, 128, and 256 mg/kg BW. After evaluating sperm parameters, the most effective dose was determined to be 32 mg/kg BW. In vivo experiments showed that treatment with OCA significantly improved sperm quality, testicular histopathology and BTB integrity, which were damaged by busulfan. Moreover, OCA intervention reduced busulfan-induced oxidative stress and autophagy in mouse testes. In vitro, OCA pretreatment (100 µM) significantly ameliorated Sertoli cell dysfunction by alleviating busulfan (800 µM)-induced oxidative stress and autophagy. Moreover, rapamycin (5 µM)-induced autophagy led to Sertoli cell barrier dysfunction, while OCA administration exerted a protective effect by alleviating autophagy. Conclusions This study demonstrated that OCA administration suppressed oxidative stress and autophagy to alleviate busulfan-induced BTB damage. These findings provide a deeper understanding of the toxicology of busulfan and a promising avenue for the development of novel OCA-based therapies for male infertility.

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Inflammasome activity regulation by PUFA metabolites

Atalay Ekiner,

Gęgotek,

Skrzydlewska

2024

Front. Immunol.

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Oxidative stress and the accompanying chronic inflammation constitute an important metabolic problem that may lead to pathology, especially when the body is exposed to physicochemical and biological factors, including UV radiation, pathogens, drugs, as well as endogenous metabolic disorders. The cellular response is associated, among others, with changes in lipid metabolism, mainly due to the oxidation and the action of lipolytic enzymes. Products of oxidative fragmentation/cyclization of polyunsaturated fatty acids (PUFAs) [4-HNE, MDA, 8-isoprostanes, neuroprostanes] and eicosanoids generated as a result of the enzymatic metabolism of PUFAs significantly modify cellular metabolism, including inflammation and the functioning of the immune system by interfering with intracellular molecular signaling. The key regulators of inflammation, the effectiveness of which can be regulated by interacting with the products of lipid metabolism under oxidative stress, are inflammasome complexes. An example is both negative or positive regulation of NLRP3 inflammasome activity by 4-HNE depending on the severity of oxidative stress. 4-HNE modifies NLRP3 activity by both direct interaction with NLRP3 and alteration of NF-κB signaling. Furthermore, prostaglandin E2 is known to be positively correlated with both NLRP3 and NLRC4 activity, while its potential interference with AIM2 or NLRP1 activity is unproven. Therefore, the influence of PUFA metabolites on the activity of well-characterized inflammasome complexes is reviewed.

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

Cited by 3 publications

References 77 publications

Ursolic acid attenuates oligospermia in busulfan-induced mice by promoting motor proteins

Ursolic acid attenuates oligospermia in busulfan-induced mice by promoting motor proteins

Octanoic acid mitigates busulfan-induced blood-testis barrier damage by alleviating oxidative stress and autophagy

Inflammasome activity regulation by PUFA metabolites

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