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Effects of bone marrow mesenchymal stem cells on ovarian and testicular function in aging Sprague-Dawley rats induced by D-galactose.

ABSTRACT: To investigate the effect of bone marrow mesenchymal stem cells (MSCs) on ovarian and testicular function of aging Sprague-Dawley (SD) rats induced by D-galactose (D-gal) and try to clarify the underlying functional mechanism. Adherent culture was used to isolate and purify rat MSCs. The status, proliferation and differentiation of MSCs were detected by hematoxylin-eosin staining, MTT, colony formation, flow cytometry and directional differentiation. The aging rat model was established by subcutaneous injection of D-gal, and the homing of MSCs was detected by fluorescence microscope after infusion of GFP-labeled MSCs through caudal vein. ELISA was used to detect the content of sex hormone in serum, and HE staining was used to observe the structure and morphology of testis and ovary. The isolated and purified MSCs were in good condition, and most of the cells were in G1 phase, which had strong abilities of cell proliferation, colony formation and differentiation. After GFP-labeled MSCs were infused, MSCs could be homed into the testis and ovary of rats. MSCs infusion could significantly improve the morphology of testis and ovary, increase the contents of P and E2 while decrease the contents of LH and FSH in female rats, and increase the content of testosterone in male rats (P < 0.01). It also increased the activity of superoxide dismutase (SOD) in serum of ovary and testis and significantly decreased the content of malondialdehyde (MDA). MSCs affected the content of MDA and the activity of SOD by reducing the expression of cyclin-dependent kinase inhibitor 2A (p16) and increasing proliferating cell nuclear antigen (PCNA), consequently improving the aging and injury of reproductive organs.

SUBMITTER: Wang Z

PROVIDER: S-EPMC7513855 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Consumption of dairy products reduces risk of type 2 diabetes. Milk proteins and fats exhibit anti-diabetic properties but milk sugars have been studied little in this context. Galactose from milk lactose is readily converted to glycogen in the liver but its effects on insulin sensitivity have not been assessed. Prebiotic oligosaccharides from milk alter gut microbiota and can thereby influence host metabolism. Our objective was to assess the effect on insulin sensitivity of dietary galactose compared to glucose and fructose, and fermentable galacto-oligosaccharides compared to non-fermentable methylcellulose. METHODS:Diets containing 15% of dry matter from glucose, fructose, galactose, galacto-oligosaccharides, or methylcellulose were fed to 36 rats per diet for 9 weeks. Hyperinsulinemic-euglycemic clamps with [3-3H]glucose infusion and a steady-state 2-[1-14C]deoxyglucose bolus injection were used to assess insulin sensitivity and glucose uptake indices. Tissue was collected in fed, fasted and fasted, insulin-stimulated states. RESULTS:Galactose increased glucose infusion rate during the clamp by 53% and decreased endogenous glucose production by 57% compared to glucose and fructose. Fed-state hepatic glycogen content was greater with galactose compared to glucose and fructose, consistent with a potentiation of the insulin effect on glycogen synthase by dephosphorylation. Galactose decreased the fecal Firmicutes:Bacteroidetes ratio while galacto-oligosaccharides increased abundance of fecal Bifidobacterium spp. 481-fold compared to methylcellulose, and also increased abundance of Lactobacillus spp. and Bacteroidetes. Galacto-oligosaccharides did not affect glucose infusion rate or endogenous glucose production during basal or clamp periods compared to methylcellulose. CONCLUSIONS:Galactose at 15% of daily intake improved hepatic insulin sensitivity in rats compared to glucose and fructose. Galactose caused an increase in fed-state hepatic glycogen content and a favourable shift in gut microbial populations. Intake of galacto-oligosaccharides improved the gut microbial profile but did not improve insulin sensitivity.

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Effects of bone marrow mesenchymal stem cells on ovarian and testicular function in aging Sprague-Dawley rats induced by D-galactose.

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