Lycium barbarum polysaccharide protects against ethanol‐induced spermiotoxicity and testicular degeneration in Immp2l ^+/− mice

Abstract

Studies have indicated that high levels of ethanol exposure impaired spermatogenesis in mice. However, the effects of chronic and low‐dose alcohol consumption on susceptible populations remain unclear. The previous studies have confirmed that Immp2l mutant mice (Immp2lTg(Tyr)979Ove or Immp2l−/−) suffered from increased levels of oxidative stress(OS) and male infertility, heterozygous lmmp2l mice (Immp2l+/−) showed no altered ROS levels under physiological condition. Lycium barbarum polysaccharide (LBP) significantly scavenge oxygen free radicals and enhance antioxidant enzyme activity. The objectives of present study were to research the effects of chronic and low‐dose alcohol‐induced damage on Immp2l+/−, explore the protective function of LBP and possible mechanism. The results indicated that chronic ethanol exposure leads to spermatogenic impairment and triggered a toxic effect on germ cell, 10 mg/kg LBP administration improved the quality of spermatozoon, decreased the ratio of apoptotic germ cells and the expression of Col1a1 and Col1a2, while increased the level of TNP2 and RPL31. In conclusion, the study may provide basic knowledge about LBP’s important role against ethanol‐induced spermiotoxicity and testicular degeneration in Immp2l+/− mice, and the mechanism may be that LBP influenced the state of the spermatogenic epithelium by decreasing the expression of Collagen level leading to alterations in protein biosynthesis during the process of spermatogenesis.

Antioxidant Behavioural Phenotype in the Immp2l Gene Knock-Out Mouse

“…An earlier truncated Immp2l mouse model ( Immp2l Tg(Tyr)979Ove ) first reported in 2008 by Lu et al [ 3 ] and which subsequently became the subject of at least 18 additional publications [ 3 , 28 , 29 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 ] presented with increased ROS and numerous associated oxidative stress phenotypes. Furthermore, this earlier truncated Immp2l Tg(Tyr)979Ove mouse had a complex genotype ( Immp2l Tg(Tyr)979Ove ) inclusive of an intragenic deletion in Immp2l and expressed a largely intact yet truncated form of Immp2l that made it difficult to determine the precise origin of the increased levels of ROS and associated oxidative stress phenotypes [ 3 ].…”

“…In addition, the earlier truncated Immp2l Tg(Tyr)979Ove mouse was developed on a blind background strain of mice (FVB/N) that made it unsuitable for behavioural examination [ 3 ]. As our primary interest is the aetiology of ASD-relevant behaviours, we developed the new Immp2l KD −/− KO mouse strain on a C57BL/6J background [ 53 ] that we demonstrate is devoid of Immp2l peptidase activity yet exhibits none of the overt oxidative stress-related phenotypes reported for the earlier truncated Immp2l Tg(Tyr)979Ove mouse model [ 3 , 28 , 29 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 ].…”

Potential role of inducible nitric oxide synthase (iNOS) activity in testicular dysfunction following co-administration of alcohol and combination antiretroviral therapy (cART) in diabetic rats: an immunohistochemistry study

“…Our results revealed that immuno-expression of caspase 3, an executioner of cell apoptosis increased significantly in testis of treated groups relative to the control, which implies increased apoptosis due to the treatments. Additionally, previous studies have reported apoptosis in the testis of animals that are diabetic [ 44 , 65 ], exposed to alcohol [ 66 , 67 ], and treated with cART [ 47 , 68 ]. Further, a significant decrease in the number of germ cells expressing Ki-67 but with strong staining intensity was recorded in the treated groups suggesting a disruption of germ cell proliferation and spermatogenesis dysfunction.…”

Mechanism of 2,4‐Dichlorophenoxyacetic acid‐induced damage to rat testis via Fas/FasL pathway and the protective effect of Lycium barbarum polysaccharides

“…LBP ( Lycium barbarum polysaccharides) has biological activities especially regarding reproductive system protection, such as enhancing immune function, antioxidation, reducing inflammation, and apoptosis 30 . Studies have shown that the protective effect of LBP on germ cells is mainly associated with the ability of LBP to enhance antioxidation, thereby reducing the level of oxidative stress and inhibiting apoptosis 31–33 . It has been reported that LBP mainly plays an anti‐inflammatory, immunomodulatory, antioxidant, and anti‐apoptotic role through the nuclear factor‐κ B, PI3K‐AKT–mTOR, p38‐MAPK, WNT‐β‐catenin, PI3K‐AKT‐GSK‐3β, and MyD88 signaling pathways 34 .…”

“…30 Studies have shown that the protective effect of LBP on germ cells is mainly associated with the ability of LBP to enhance antioxidation, thereby reducing the level of oxidative stress and inhibiting apoptosis. [31][32][33] It has been reported that LBP mainly plays an antiinflammatory, immunomodulatory, antioxidant, and anti-apoptotic role through the nuclear factor-κ B, PI3K-AKT-mTOR, p38-MAPK, WNTβ-catenin, PI3K-AKT-GSK-3β, and MyD88 signaling pathways. 34 However, it remains to be determined, whether LBP also reduces the expression of Fas/FasL signaling pathway proteins, which would result in a protective effect.…”