Reproductive Technologies and Parkinson’s disease: A Study of the Substantia Nigra and Motor Functions in C57BL/6 and B6.CG-TG Mice

Parkinson’s disease (PD) is an age-related neurodegenerative pathology characterized by abnormalities of the brain’s dopaminergic system, alpha-synucleinopathy, and motor dysfunction. A possible association of assisted reproductive technologies (ARTs) with neuropathologies is discussed in the medical literature, but there is a lack of experimental studies addressing this issue. Here, we investigated the effects of ARTs, namely in vitro culture of preimplantation embryos and embryo transfer (ET), on the manifestation of traits characteristic of PD in offspring, such as motor dysfunction, reduced density of neurons (including the dopaminergic), and alpha-synuclein accumulation in the substantia nigra pars compacta (SNpc) of the brain. Male offspring of the mouse strains B6.Cg-Tg and C57BL/6 (hereinafter referred to as wild type, WT), born via ART (groups B6.Cg-Tg ET and WT ET) or natural mating (groups B6.Cg-Tg CTL and WT CTL), were tested at the age of six months. Motor coordination and body balance were studied using the rotarod test; neuronal density and alpha-synuclein accumulation in the SNpc were assessed immunohistochemically. B6.Cg-Tg mice born without using ART (B6.Cg-Tg CTL) were found to be characterized by a low density of neurons (including the dopaminergic) and alpha-synuclein accumulation in the SNpc neurons compared to wild type mice (WT CTL). WT offspring born via ART (WT ET group) were characterized by impaired motor coordination and body balance, as well as by a reduced density of SNpc neurons (including the dopaminergic). The offspring of the B6.Cg-Tg mice born via ART (B6.Cg-Tg ET group) were characterized by an increased alpha-synuclein accumulation in SNpc neurons. The results of our study suggest a possible link between the use of modern ARTs and the increased predisposition to neurodegenerative processes, including the manifestation of signature features of the PD phenotype in offspring.