In vitro exposure to metformin activates human spermatozoa at therapeutically relevant concentrations
Abstract
Abstract Background Metformin, a drug used to treat type 2 diabetes, has gained attention for its multiple therapeutic applications. However, little is known about its effects on human sperm function at therapeutically relevant concentration. Objectives The aim of this study was to elucidate the in vitro actions of metformin on human sperm function and explore the underlying mechanism of any effects. Materials and methods Human ejaculated spermatozoa were treated with therapeutically relevant concentrations (0.25, 5, 10, 20, 40, and 80 µM) of metformin in vitro. Fertilization‐essential functions of spermatozoa were examined, including viability, motility, capacitation, acrosome reaction, hyperactivation, and penetration ability. The signaling pathways mediated by 5′‐AMP‐activated protein kinase (AMPK), intracellular calcium concentration ([Ca2+]i), and tyrosine phosphorylation of spermatozoa were also measured. Results Although metformin did not affect sperm viability, motility, and [Ca2+]i, it significantly increased the percentages of capacitated spermatozoa, acrosomal‐reacted spermatozoa, and hyperactivated spermatozoa as well as penetration ability of human spermatozoa at the concentrations of 40 and 80 µM (P < .05). These concentrations of metformin also elevated the levels of phosphorylated AMPK and tyrosine phosphorylation in human spermatozoa. In addition, activation of AMPK by A769662 (an AMPK activator) had similar effects to metformin on human spermatozoa, while…
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