Pregnancy at Advanced Maternal Age Affects Behavior and Hippocampal Gene Expression in Mouse Offspring.
There is growing evidence that advanced maternal age is a risk factor for neurological and neuropsychiatric disorders in offspring. However, it remains unclear whether the altered brain programming induced by advanced maternal age is mediated by pre- or postnatal factors. Here, a mouse model was used to investigate whether pregnancy at advanced age may provoke behavioral and brain gene expression changes in offspring. Swiss Albino mice conceived by 3-month-old males and either 15-18-month-old (n = 11) or 3-month-old control females (n = 5), were delivered by cesarean section, fostered after birth by 3-month-old dams and subjected to a battery of behavioral tests. Furthermore, genome-wide mRNA expression was analyzed in the hippocampi of 4-month-old males offspring using microarrays. Offspring conceived by old mothers exhibited increased ultrasound vocalization activity during separation from the foster mother, increased anxiety-like behaviors in adult life, and altered patterns of hippocampal gene expression, compared to controls. These effects were not reversed by the postnatal maternal care provided by the young foster mothers, suggesting that the altered brain programming is already established at birth, consistent with prenatal effects related to maternal aging.
Department of Experimental Embryology, Institute of Genetics and Animal Breeding of the Polish Academy of Sciences, Jastrzebiec, Poland.|Faculty of Veterinary Medicine, University of Teramo, Italy.
Silvestre
S
Sampino
Department of Molecular Biology, Institute of Genetics and Animal Breeding of The Polish Academy of Sciences, Jastrzebiec, Poland.
Adrian Mateusz
AM
Stankiewicz
Department of Experimental Embryology, Institute of Genetics and Animal Breeding of the Polish Academy of Sciences, Jastrzebiec, Poland.
Federica
F
Zacchini
Faculty of Computer Science, Bialystok University of Technology, Poland.
Joanna
J
Goscik
Department of Genomics and Biodiversity, Institute of Genetics and Animal Breeding of The Polish Academy of Sciences, Jastrzebiec, Poland.
Agnieszka
A
Szostak
Faculty of Biology, University of Gdansk, Poland.|Department of Pharmacology, Toxicology and Neuroscience, Louisiana State University Health Sciences Center, Shreveport.
Artur Hugo
AH
Swiergiel
Laboratory of Clinical Epidemiology, Institute of Biomedicine and Molecular Immunology, National Research Center of Italy, Palermo.
Gaspare
G
Drago
Department of Experimental Embryology, Institute of Genetics and Animal Breeding of the Polish Academy of Sciences, Jastrzebiec, Poland.
Jacek Andrzej
JA
Modlinski
Department of Experimental Embryology, Institute of Genetics and Animal Breeding of the Polish Academy of Sciences, Jastrzebiec, Poland.|Faculty of Veterinary Medicine, University of Teramo, Italy.|Department of Animal Reproduction Biotechnology, National Research Institute of Animal Production, Balice, Poland.
Grazyna Ewa
GE
Ptak
D000367:Age Factors; D000818:Animals; D001007:Anxiety / Q000235:genetics* / Q000378:metabolism; D001522:Behavior, Animal; D004195:Disease Models, Animal; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D008423:Maternal Age; D051379:Mice; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011270:Pregnancy, Animal; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D013315:Stress, Psychological / Q000235:genetics* / Q000378:metabolism
D012333:RNA, Messenger
Brain disorders; Delayed motherhood; Maternal effects