Maternal lipopolysaccharide exposure results in glucose metabolism disorders and sex hormone imbalance in male offspring.

An adverse intrauterine environment may be an important factor contributing to the development of type 2 diabetes in later life. The present study investigated the longitudinal effects of maternal lipopolysaccharide (LPS) exposure during the third trimester on glucose metabolism and sex hormone balance in the offspring. Pregnant mice were intraperitoneally injected with LPS (50 µg/kg) daily from gestational day (GD) 15 to GD17. Glucose tolerance test (GTT) and insulin tolerance test (ITT) were assessed at postnatal day (PND) 60 and PND120. Sex hormones, their receptors, and metabolic enzymes (aromatase) were measured in male offspring at different phases of development (PND14: juvenile; PND35: adolescence; PND60: adulthood; and PND120: middle age). LPS-exposed male offspring exhibited glucose intolerance and insulin resistance by GTT and ITT at middle age, accompanied by an increase in fasting blood glucose and reductions in serum insulin levels and hepatic phosphorylated (p) -AKT/AKT ratio. However, glucose intolerance and insulin resistance were not observed in LPS-exposed female offspring. Maternal LPS exposure upregulated hepatic aromatase proteins and mRNA levels in male offspring at all time points. At adolescence, the testosterone/estradiol ratio (T/E2) was markedly reduced in LPS-exposed male offspring. Moreover, maternal LPS exposure significantly increased hepatic estrogen receptor (ER) α expressions and decreased hepatic androgen receptor (AR) expressions in male offspring. At adulthood, maternal LPS exposure increased serum estradiol levels, decreased serum testosterone levels and elevated hepatic ERß expressions in male offspring. In conclusion, maternal LPS exposure upregulated aromatase expressions, followed by a reduction in the T/E2 ratio and an alteration in sex hormone receptor activity, which might be involved in the development of glucose metabolism disorders in middle-aged male offspring. This study provides a novel clue and direction to clarify the pathogenesis of maternal infection-related diabetes in male offspring.

Folic Acid Promotes Wound Healing in Diabetic Mice by Suppression of Oxidative Stress.

The aim of this study was to investigate the effects of folic acid on impaired wound healing in diabetic mice. Male mice were divided into three groups: group 1, the non-diabetic mice (control); group 2, the streptozotocin (STZ)-induced type 1 diabetic mice; and group 3, the diabetic mice that received a daily dose of 3 mg/kg folic acid via oral gavage. Full-thickness excision wounds were created with 8-mm skin biopsy punches. Each wound closure was continuously evaluated until the wound healed up. Wound healing was delayed in diabetic mice compared with the non-diabetic mice. There were significantly reduced levels of hydroxyproline content (indicator of collagen deposition) and glutathione in diabetic wounds, whereas levels of lipid peroxidation and protein nitrotyrosination were increased. Daily supplementation with folic acid restored diabetes-induced healing delay. Histopathology showed that folic acid supplementation accelerated granulation tissue formation, proliferation of fibroblasts, and tissue regeneration in diabetic mice. Interestingly, folic acid alleviated diabetes-induced impaired collagen deposition in wounds. Moreover, folic acid significantly decreased levels of lipid peroxidation, protein nitrotyrosination and glutathione depletion in diabetic wounds. In conclusion, our results indicate that folic acid supplementation may improve impaired wound healing via suppressing oxidative stress in diabetic mice.