Prepubertal exposure to gadolinium-based contrast agents impairs sperm quality and elevates oxidative stress in adult rats

Abstract

Gadolinium-based contrast agents (GBCAs) are widely used in magnetic resonance imaging. Gadolinium (Gd) retention has been reported in various tissues of both patients and experimental animals, even in those with normal renal and hepatic function and an intact blood-brain barrier. Gadoteric Acid (Dotarem®) is approved for use in children of all ages, including neonates. In these groups, the blood-tissue barriers in the male reproductive tract are still developing, which may lead to more pronounced Gd retention than in adults. The aim of this study was to evaluate the effects of a single prepubertal exposure (15 days postnatal, pnd) to gadoteric acid (Gadoterate meglumine - Dotarem®) on sperm quality and quantity in adult rats. Male rats were treated with a single dose of gadoteric acid at a clinical-equivalent dose (0.6 mMol/kg) or at one-tenth that dose (0.06 mMol/kg), at 15pnd (prepubertal phase). The rats were euthanized at 110pnd (adult phase). Gd-treated animals exhibited reduced testicular and epididymal weights, decrease daily sperm production, and increased epididymal sperm transit time. Sperm motility, viability, morphology, mitochondrial function, acrosomal and DNA integrity, and chromatin compaction were also negatively affected. Furthermore, increased oxidative stress markers and lipid peroxidation were observed in sperm and testicular tissue. A single prepubertal exposure to Gd, before the establishment of testicular and epididymal barriers, may lead to long-term alterations in sperm quantitative and qualitative parameters and induce oxidative stress in sperm and male reproductive tissues in adulthood.