Increased sperm deoxyribonucleic acid damage leads to poor embryo quality and subfertility of male rats treated with methylphenidate hydrochloride in adolescence

Author(s)

da Costa Nunes Gomes, Ana Clara ; Bellin, Camila Souza ; Dias, Stephanie da Silva ; de Rosa, Thalita de Queiroz ; de Araujo, Marina Pereira ; Miraglia, Sandra Maria ; Mendes, Talita Biude ; Vendramini, Vanessa

• Document type: Journal article
• Source: ANDROLOGY; v. 10, n. 8, p. 12-pg., 2022-09-02.

Abstract

Background Methylphenidate hydrochloride (MPH) is a psychostimulant widely used in the treatment of attention-deficit hyperactive disorder (ADHD), as well as a performance enhancer, for at least 60 years. Despite the notable effectiveness as a psychostimulant, ADHD is a chronic disorder and has a two-third chance of accompanying the individual throughout life. Long-term use of MPH has been associated not only with an increase in the development of neurodegenerative diseases, but it also causes side effects on male fertility in experimental animals. Objectives To investigate whether methylphenidate poses a risk to sperm DNA structure and to the quality of embryos conceived after treatment during adolescence in rats. Materials and methods Wistar rats at 38 days of age were treated either with 5 mg/kg body weight of MPH, in a single daily dose for 30 days, via gavage or with distilled water-only protocol. Levels of oxidative stress in testicular and epididymal tissues were evaluated. Sperm chromatin quality and acrosome integrity was assessed under flow cytometry. From 107 days of age, animals were mated with untreated females. The effects of the paternal contribution at two different embryo development moments-cleavage stage (2.5 days post coitum) and late gestation (20 days post coitum) -were analyzed. Results MPH caused high levels of sperm DNA damage, which was reflected in 40% of decrease in early embryo quality and a lower number of live pups at 20 dpc. Discussion The high level of fragmentation seen in the embryos sired from the MPH group is consistent with the poor chromatin structure of the sperm and does not seem to be a result of oxidative stress in the reproductive tissues. Conclusions The results presented here suggest that the subchronic use of MPH during male prepubertal phase may cause long-term subfertility and compromise embryo survival. (AU)

• FAPESP's process: 17/09712-4 - Effect of methylphenidate hydrochloride (Ritalin®) on paternal fertility and on the quality of the embryos conceived after chronic treatment of rats at adolescence
• Grantee: Stephanie da Silva Dias
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 17/09725-9 - Effect of methylphenidade hydrochloride (Ritalin®) on the quality of sperm genome and function in rats treated at adolescence
• Grantee: Camila Souza Bellin
• Support Opportunities: Scholarships in Brazil - Scientific Initiation