Reproductive Technologies and Parkinson’s disease: A Study of the Substantia Nigra and Motor Functions in C57BL/6 and B6.CG-TG Mice
摘要
Parkinson’s disease (PD) is an age-related neurodegenerativepathology characterized by abnormalities of the brain’s dopaminergicsystem, alpha-synucleinopathy, and motor dysfunction. A possibleassociation of assisted reproductive technologies (ARTs) with neuropathologiesis discussed in the medical literature, but there is a lack of experimentalstudies addressing this issue. Here, we investigated the effectsof ARTs, namely in vitro culture of preimplantation embryos andembryo transfer (ET), on the manifestation of traits characteristicof PD in offspring, such as motor dysfunction, reduced density ofneurons (including the dopaminergic), and alpha-synuclein accumulationin the substantia nigra pars compacta (SNpc) of the brain.Male offspring of the mouse strains B6.Cg-Tg and C57BL/6 (hereinafterreferred to as wild type, WT), born via ART (groups B6.Cg-Tg ETand WT ET) or natural mating (groups B6.Cg-Tg CTL and WT CTL), weretested at the age of six months. Motor coordination and body balancewere studied using the rotarod test; neuronal density and alpha-synuclein accumulationin the SNpc were assessed immunohistochemically. B6.Cg-Tg mice bornwithout using ART (B6.Cg-Tg CTL) were found to be characterizedby a low density of neurons (including the dopaminergic) and alpha-synucleinaccumulation in the SNpc neurons compared to wild type mice (WT CTL).WT offspring born via ART (WT ET group) were characterized by impairedmotor coordination and body balance, as well as by a reduced densityof SNpc neurons (including the dopaminergic). The offspring of theB6.Cg-Tg mice born via ART (B6.Cg-Tg ET group) were characterizedby an increased alpha-synuclein accumulation in SNpc neurons. Theresults of our study suggest a possible link between the use ofmodern ARTs and the increased predisposition to neurodegenerativeprocesses, including the manifestation of signature features ofthe PD phenotype in offspring.