Ziętek Marta Marlena, Jaszczyk Aneta, Stankiewicz Adrian Mateusz, Sampino Silvestre
Department of Experimental Embryology, Institute of Genetics and Animal Biotechnology of the Polish Academy of Sciences, Jastrzębiec, Poland.
Department of Animal Behavior and Welfare, Institute of Genetics and Animal Biotechnology of the Polish Academy of Sciences, Jastrzębiec, Poland.
Sci Rep. 2024 Dec 30;14(1):31733. doi: 10.1038/s41598-024-82070-x.
Autism spectrum disorders encompass diverse neurodevelopmental conditions marked by alterations in social communication and repetitive behaviors. Advanced maternal age is associated with an increased risk of bearing children affected by autism but the etiological factors underlying this association are not well known. Here, we investigated the effects of advanced maternal age on offspring health and behavior in two genetically divergent mouse strains: the BTBR T Itpr3/J (BTBR) mouse model of idiopathic autism, and the C57BL/6 J (B6) control strain, as a model of genetic variability. In both strains, advanced maternal age negatively affected female reproductive and pregnancy outcomes, and perturbed placental and fetal growth, and the expression of genes in the fetal brain tissues. Postnatally, advanced maternal age had strain-dependent effects on offspring sociability, learning skills, and the occurrence of perseverative behaviors, varying between male and female offspring. These findings disentangle the relationship between genetic determinants and maternal age-related factors in shaping the emergence of autism-like behaviors in mice, highlighting the interplay between maternal age, genetic variability, and prenatal programming, in the occurrence of neurodevelopmental disorders.
自闭症谱系障碍包括多种神经发育状况，其特征是社交沟通和重复行为发生改变。高龄产妇生育患自闭症子女的风险增加，但这种关联背后的病因尚不清楚。在此，我们研究了高龄产妇对两种基因不同的小鼠品系后代健康和行为的影响：作为特发性自闭症小鼠模型的BTBR T Itpr3/J（BTBR）小鼠，以及作为遗传变异性模型的C57BL/6 J（B6）对照品系。在这两个品系中，高龄产妇均对雌性生殖和妊娠结局产生负面影响，扰乱胎盘和胎儿生长以及胎儿脑组织中的基因表达。出生后，高龄产妇对后代的社交能力、学习技能和持续性行为的发生具有品系依赖性影响，且在雌雄后代之间存在差异。这些发现厘清了基因决定因素与母亲年龄相关因素在塑造小鼠自闭症样行为出现过程中的关系，突出了母亲年龄、遗传变异性和产前编程在神经发育障碍发生中的相互作用。
