Dietary ω3-and ω6-Polyunsaturated fatty acids reconstitute fertility of Juvenile and adult Fads2-Deficient mice

Stoffel, Wilhelm; Schmidt‐Soltau, Inga; Binczek, Erika; Thomas, Andreas; Thevis, Mario; Wegner, Ina

doi:10.1016/j.molmet.2020.100974

Cited by 43 publications

(31 citation statements)

References 47 publications

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“…One reason could be the deficiency of highly unsaturated fatty acids. However, this defect can be reversed by docosahexaenoic acid (DHA) in the diet [218][219][220][221]. Male Elovl2 −/− mice, as expected, also displayed arrested spermatogenesis and infertility, which supports the idea that PUFAs with 24-30 carbons of the ω-6 family are required for normal sperm formation and male fertility.…”

Section: Lipid Metabolism-related Knockout Mice Modelsupporting

confidence: 59%

Sperm Lipid Markers of Male Fertility in Mammals

Shan

Hirschfeld

et al. 2021

IJMS

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Sperm plasma membrane lipids are essential for the function and integrity of mammalian spermatozoa. Various lipid types are involved in each key step within the fertilization process in their own yet coordinated way. The balance between lipid metabolism is tightly regulated to ensure physiological cellular processes, especially referring to crucial steps such as sperm motility, capacitation, acrosome reaction or fusion. At the same time, it has been shown that male reproductive function depends on the homeostasis of sperm lipids. Here, we review the effects of phospholipid, neutral lipid and glycolipid homeostasis on sperm fertilization function and male fertility in mammals.

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Section: Lipid Metabolism-related Knockout Mice Modelsupporting

confidence: 59%

Sperm Lipid Markers of Male Fertility in Mammals

Shan

Hirschfeld

et al. 2021

IJMS

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“…Increase oxidative stress may cause ROS-mediated damage to macromolecules and critical enzymes involved in testicular steroidogenesis and spermatogenesis, besides lipid peroxidation of the germ cell membrane that is rich in polyunsaturated fatty acids. [72][73][74] Furthermore, the testis and epididymis of rats treated with DOX exhibited marked (p < 0.05) increased in XO activity. The activity of XO in this study may have increased following an increase in the concentration of Ca 2þ since excess Ca 2þ activates the protease Calpain, which converts xanthine dehydrogenase (XDH) into XO.…”

Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Luteolin abates reproductive toxicity mediated by the oxido-inflammatory response in Doxorubicin-treated rats

Owumi

Ijadele

Arunsi

et al. 2020

Toxicology Research and Application

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The anti-neoplastic use of Doxorubicin (DOX) is hampered by several limitations, including reproductive toxicity. Luteolin (LUT)–a phytochemical-biological benefits include antioxidative and anti-inflammatory actions. Here we examined the protective effect of LUT against DOX-induced reproductive toxicity in an in vivo model—male albino Wistar rats—randomly assigned to five groups and treated as follows: Control (corn oil 2 mL/kg; per os), LUT (100 mg/kg; per os), DOX (2 mg/kg) by intraperitoneal injections, co-treated groups received LUT (50 and 100 mg/kg) with DOX. Treatment with DOX alone, significantly (p > 0.05), reduced biomarkers of testicular function, reproductive hormone levels, testicular and epididymal antioxidant, and anti-inflammatory cytokine. DOX increased (p > 0.05) sperm morphological abnormalities, as well as reactive oxygen and nitrogen species, lipid peroxidation, xanthine oxidase, a pro-inflammatory cytokine, and apoptotic biomarkers. Furthermore, testicular and epididymal histological lesion complemented the observed biochemical changes in treated rats. LUT co-treatment resulted in a dosage-dependent improvement in rats’ survivability, antioxidants capacity, reduction in biomarkers of oxidative stress, pro-inflammatory cytokines, and apoptosis in rat’s testis and epididymis. Also, LUT treatment resulted in improved histological features in the testis and epididymis, relative to DOX alone treated rats. LUT co-treatment abated DOX-mediated reproductive organ injuries associated with pro-oxidative, inflammatory, and apoptotic mechanisms. LUT supplementation may serve as a phyto-protective agent in alleviating male reproductive organ toxic injuries associated with Doxorubicin therapy.

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“…Mice were perfused from the left ventricle with cold PBS, then with PBS and PBS-buffered 4% paraformaldehyde. Tissues were fixed and processed for light- and immunofluorescence microscopy as described before [ 12 ].…”

Section: Methodsmentioning

confidence: 99%

“…To study underlying genetic and epigenetic mechanisms of this polygenic disorder, genetically defined null allelic murine strains, including the LDLR-deficient mutant ( ldlr −/−), lacking the LDL-receptor for LDL uptake, and the ApoE- ( apoe −/−) mutant, devoid of the remnant and VLDL-ligand for cholesterol clearance by the LDL and LRP (LDL-receptor related), have been generated by transgenic techniques [ 5 ]. These two strains rapidly develop extensive atherosclerosis throughout the entire aorta and are congenial models for nutrition studies implementing atherogenic HFHC (“Western”) diets [ [5] , [6] , [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] ] .…”

Section: Introductionmentioning

confidence: 99%

High fat / high cholesterol diet does not provoke atherosclerosis in the ω3-and ω6-polyunsaturated fatty acid synthesis–inactivated Δ6-fatty acid desaturase–deficient mouse

Stoffel

Binczek

Schmidt‐Soltau

et al. 2021

Molecular Metabolism

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Objective An increased ω6/ω3-polyunsaturated fatty acid ratio in the current Western diet is regarded as a critical epigenetic nutritional factor in the pathogenesis of several human lifestyle diseases, metabolic syndrome, cardiovascular disease, the central nervous system and the female and male reproductive systems. The impact of nutrient ω3-and ω6-PUFAs in the pathogenesis of dyslipoproteinemia and atherosclerosis has been a topic of intense efforts for several decades. Cellular homeostasis of the ω3-and ω6- PUFA pool is maintained by the synthesis of ω3-and ω6-PUFAs from essential fatty acids (EFA) (linoleic and α-linolenic acid) and their dietary supply. In this study, we used the auxotrophic Δ6-fatty acid desaturase- (FADS2) deficient mouse ( fads2 −/−), an unbiased model congenial for stringent feeding experiments, to investigate the molecular basis of the proposed protective role of dietary ω3-and ω6-PUFAs (Western diet) in the pathogenesis of multifactorial dyslipoproteinemia and atherosclerosis. We focused on the metabolic axis—liver endoplasmic reticulum (ER), serum lipoprotein system (Lp) and aorta vessel wall. Furthermore, we addressed the impact of the inactivated fads2 -locus with inactivated PUFA synthesis on the development and progression of extended atherosclerosis in two different mouse mutants with disrupted cholesterol homeostasis, using the apoe −/− and ldlr −/− mutants and the fads2 −/− x apoe −/− and fads2 −/− x ldlr −/− double mutants. Methods Cohorts of +/+ and fads2 −/− mice underwent two long-term dietary regimens: a) a PUFA-free standard chow diet containing only EFAs, essential for viability, and b) a high fat/high cholesterol (HFHC) diet, a mimicry of the human atherogenic “Western” diet. c) To study the molecular impact of PUFA synthesis deficiency on the development and progression of atherosclerosis in the hypercholesterolemic apoe −/− and ldlr −/− mouse models fed PUFA-free regular and sustained HFHC diets, we generated the fads2 −/− x apoe −/− and the fads2 −/− x ldlr −/− double knockout mutants. We assessed essential molecular, biochemical and cell biological links between the diet-induced modified lipidomes of the membrane systems of the endoplasmic reticulum/Golgi complex, the site of lipid synthesis, the PL monolayer and neutral lipid core of LD and serum-Lp profiles and cellular reactions in the aortic wall. Results ω3-and ω6-PUFA synthesis deficiency in the fads2 −/− mouse causes a) hypocholesterolemia and hypotriglyceridemia, b) dyslipoproteinemia with a shi...

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Dietary ω3-and ω6-Polyunsaturated fatty acids reconstitute fertility of Juvenile and adult Fads2-Deficient mice

Cited by 43 publications

References 47 publications

Sperm Lipid Markers of Male Fertility in Mammals

Sperm Lipid Markers of Male Fertility in Mammals

Luteolin abates reproductive toxicity mediated by the oxido-inflammatory response in Doxorubicin-treated rats

High fat / high cholesterol diet does not provoke atherosclerosis in the ω3-and ω6-polyunsaturated fatty acid synthesis–inactivated Δ6-fatty acid desaturase–deficient mouse

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