Department of Morphology and Genetics, Laboratory of Reproductive and Developmental Biology (LaBReD), Paulista School of Medicine, Federal University of Sao Paulo-EPM/UNIFESP, Sao Paulo, Brazil.
Paulista School of Nursing, Federal University of Sao Paulo-EPE/UNIFESP, Sao Paulo, Brazil.
Andrology. 2022 Nov;10(8):1632-1643. doi: 10.1111/andr.13277. Epub 2022 Sep 2.
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.
To investigate whether methylphenidate poses a risk to sperm DNA structure and to the quality of embryos conceived after treatment during adolescence in rats.
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.
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.
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.
The results presented here suggest that the subchronic use of MPH during male prepubertal phase may cause long-term subfertility and compromise embryo survival.
盐酸哌甲酯（MPH）是一种广泛用于治疗注意力缺陷多动障碍（ADHD）的精神兴奋剂，也是一种性能增强剂，至少已有 60 年的历史。尽管作为一种精神兴奋剂具有显著的效果，但 ADHD 是一种慢性疾病，有三分之二的可能性会伴随个体终生。长期使用 MPH 不仅与神经退行性疾病的发展增加有关，而且还会对实验动物的男性生育力产生副作用。
研究盐酸哌甲酯是否会对青春期大鼠在治疗期间产生的精子 DNA 结构和胚胎质量造成风险。
38 天大的 Wistar 大鼠每天通过灌胃接受 5mg/kg 体重的 MPH 或仅接受蒸馏水处理，持续 30 天。评估睾丸和附睾组织中的氧化应激水平。通过流式细胞术评估精子染色质质量和顶体完整性。从 107 天大开始，动物与未经处理的雌性动物交配。分析父本在两个不同胚胎发育时刻（合子后 2.5 天和晚期妊娠 20 天）的贡献。
MPH 导致精子 DNA 损伤水平升高，这反映在早期胚胎质量降低了 40%，20 天妊娠时活产幼崽数量减少。
MPH 组胚胎中出现的高碎片率与精子染色质结构差一致，似乎不是生殖组织中氧化应激的结果。
这里提出的结果表明，雄性青春期前阶段的亚慢性 MPH 使用可能导致长期的低生育力和胚胎存活率降低。
