Advanced paternal age directly impacts mouse embryonic placental imprinting

Autor: Blair R. McCallie, Jason C. Parks, William B. Schoolcraft, Michelle M. Denomme, Nathan McCubbin, Mandy G. Katz-Jaffe
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Male
Embryology
Aging
medicine.risk_factor
Physiology
Placenta
Intrauterine growth restriction
Artificial Gene Amplification and Extension
Biochemistry
Polymerase Chain Reaction
Epigenesis
Genetic
Epigenome
Fathers
Mice
0302 clinical medicine
Animal Cells
Pregnancy
Medicine and Health Sciences
Imprinting (psychology)
030219 obstetrics & reproductive medicine
Multidisciplinary
DNA methylation
KCNQ1OT1
Reproduction
Chromatin
Nucleic acids
Medicine
Epigenetics
Female
Anatomy
Cellular Types
DNA modification
Chromatin modification
Research Article
Chromosome biology
Cell biology
Offspring
Science
Biology
Research and Analysis Methods
Paternal Age
Andrology
03 medical and health sciences
Genomic Imprinting
medicine
Genetics
Animals
Humans
Paternal age effect
Molecular Biology Techniques
Molecular Biology
Biology and life sciences
Reproductive System
DNA
medicine.disease
Sperm
030104 developmental biology
Germ Cells
Infertility
Gene expression
Genomic imprinting
Physiological Processes
Organism Development
Developmental Biology
Zdroj: PLoS ONE
PLoS ONE, Vol 15, Iss 3, p e0229904 (2020)
ISSN: 1932-6203
Popis: The placental epigenome plays a critical role in regulating mammalian growth and development. Alterations to placental methylation, often observed at imprinted genes, can lead to adverse pregnancy complications such as intrauterine growth restriction and preterm birth. Similar associations have been observed in offspring derived from advanced paternal age fathers. As parental age at time of conception continues to rise, the impact of advanced paternal age on these reproductive outcomes is a growing concern, but limited information is available on the molecular mechanisms affected in utero. This longitudinal murine research study thus investigated the impact of paternal aging on genomic imprinting in viable F1 embryonic portions of the placentas derived from the same paternal males when they were young (4-6 months) and when they aged (11-15 months). The use of a controlled outbred mouse model enabled analysis of offspring throughout the natural lifetime of the same paternal males and excluded confounding factors like female age or infertility. Firstly, paternal age significantly impacted embryonic placental weight, fetal weight and length. Targeted bisulfite sequencing was utilized to examine imprinted methylation at the Kcnq1ot1 imprinting control region, with significant hypermethylation observed upon natural paternal aging. Quantitative real-time PCR assessed imprinted gene expression levels at various imprinting clusters, resulting in transcript level alterations attributable to advanced paternal age. In summary, our results demonstrate a paternal age effect with dysregulation at numerous imprinted loci, providing a mechanism for future adverse placental and offspring health conditions.
Databáze: OpenAIRE
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