Metformin treatment of high-fat diet-fed obese male mice restores sperm function and fetal growth, without requiring weight loss
Nicole O. McPherson, Michelle Lane
Abstract
(n = 8) for 6 weeks. Animals fed with CD continued on a CD (n = 9). Males were mated with fertile C57BL6 females for the assessment of pregnancy and fetal growth. Sperm motility, spermatozoa and testicular morphology, sperm-zona pellucida binding, sperm reactive oxygen species (ROS) (intracellular [DCFDA], superoxide [MSR], and oxidative DNA lesions [8OHdG]), and mitochondrial membrane potential (JC1) were assessed. Metformin treatment of HFD males improved glucose tolerance (+12%, P < 0.05) and reduced Homeostatic Model Assessment of Insulin Resistance (HOMA-IR; -36%, P < 0.05). This occurred in the absence of a change in body weight or adiposity. Metformin treatment of HFD-fed males restored testicular morphology (+33%, P < 0.05), sperm motility (+66%, P < 0.05), sperm-zona pellucida binding (+25%, P < 0.05), sperm intracellular ROS concentrations (-32%, P < 0.05), and oxidative DNA lesions (-45%, P < 0.05) to the levels of the CD males. Metformin treatment of HFD fathers increased fetal weights and lengths compared with those born to HFD fathers (+8%, P < 0.05), with fetal lengths restored to those of fetuses of CD males. Short-term metformin treatment in men who are obese could be a potential intervention for the treatment of subfertility, without the need for a reduction in body weight/adiposity.