dc.contributor.author
Zhang, Xiaoli
dc.contributor.author
Reichetzeder, Christoph
dc.contributor.author
Liu, Yvonne
dc.contributor.author
Hocher, Johann-Georg
dc.contributor.author
Hasan, Ahmed A.
dc.contributor.author
Lin, Ge
dc.contributor.author
Kleuser, Burkhard
dc.contributor.author
Hu, Liang
dc.contributor.author
Hocher, Berthold
dc.date.accessioned
2024-04-17T07:09:54Z
dc.date.available
2024-04-17T07:09:54Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/43284
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-43000
dc.description.abstract
Background: Preclinical animal studies and clinical studies indicate that both maternal as well as paternal genetic alterations/gene defects might affect the phenotype of the next-generation without transmissions of the affected gene. Currently, the question of whether the same genetic defect present in the mother or father leads to a similar phenotype in the offspring remains insufficiently elucidated.
Methods: In this head-to-head study, we crossbred female and male mice with heterozygous endothelial eNOS knockout (eNOS+/−) with male and female wild-type (wt) mice, respectively. Subsequently, we compared the phenotype of the resulting wt offspring with that of wt offspring born to parents with no eNOS deficiency.
Results: Wt female offspring of mothers with heterozygous eNOS showed elevated liver fat accumulation, while wt male offspring of fathers with heterozygous eNOS exhibited increased fasting insulin, heightened insulin levels after a glucose load, and elevated liver glycogen content. By quantitative mass-spectrometry it was shown that concentrations of six serum metabolites (lysoPhosphatidylcholine acyl C20:3, phosphatidylcholine diacyl C36:2, phosphatidylcholine diacyl C38:1, phosphatidylcholine acyl-alkyl C34:1, phosphatidylcholine acyl-alkyl C36:3, and phosphatidylcholine acyl-alkyl C42:5 (PC ae C42:5) as well as four liver carbon metabolites (fructose 6-phosphate, fructose 1,6-bisphosphate, glucose 6-phosphate and fumarate) were different between wt offspring with eNOS+/− mothers and wt offspring with eNOS+/− fathers. Importantly, fumarate was inversely correlated with the liver fat accumulation in female offspring with eNOS+/− mothers and increased liver glycogen in offspring of both sexes with eNOS+/− fathers. The qRT-PCR results revealed that the gene expression patterns were different between wt offspring with eNOS+/− mothers and those offspring with eNOS+/− fathers. Different gene expression patterns were correlated with different observed phenotypic changes in male/female offspring born to mothers or fathers with a heterozygous eNOS genotype.
Conclusion: The identical parental genetic alteration (heterozygous eNOS deficiency), without being passed on to the offspring, results in distinct metabolic, liver phenotype, and gene expression pattern variations depending on whether the genetic alteration originated from the father or the mother.
en
dc.format.extent
13 Seiten
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
maternal and paternal programming
en
dc.subject
metabolomics
en
dc.subject
sex-dependent effects
en
dc.subject.ddc
500 Naturwissenschaften und Mathematik::570 Biowissenschaften; Biologie::570 Biowissenschaften; Biologie
dc.title
Parental sex-dependent effects of either maternal or paternal eNOS deficiency on the offspring’s phenotype without transmission of the parental eNOS deficiency to the offspring
dc.type
Wissenschaftlicher Artikel
dc.date.updated
2024-04-12T12:53:17Z
dcterms.bibliographicCitation.articlenumber
1306178
dcterms.bibliographicCitation.doi
10.3389/fphys.2023.1306178
dcterms.bibliographicCitation.journaltitle
Frontiers in Physiology
dcterms.bibliographicCitation.volume
14
dcterms.bibliographicCitation.url
https://doi.org/10.3389/fphys.2023.1306178
refubium.affiliation
Biologie, Chemie, Pharmazie
refubium.affiliation.other
Institut für Pharmazie
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.isPartOf.eissn
1664-042X
refubium.resourceType.provider
DeepGreen