Epigenetic modification of fetal baboon hepatic phosphoenolpyruvate carboxykinase following exposure to moderately reduced nutrient availability.
Decreased maternal nutrient availability during pregnancy induces compensatory fetal metabolic and endocrine responses. Knowledge of cellular changes involved is critical to understanding normal and abnormal development. Several studies in rodents and sheep report increased fetal plasma cortisol and associated increased gluconeogenesis in response to maternal nutrient reduction (MNR) but observations in primates are lacking. We determined MNR effects on fetal liver phosphoenolpyruvate carboxykinase 1 (protein, PEPCK1; gene, PCK1 orthologous/homologous human chromosomal region 20q13.31) at 0.9 gestation (G). Female baboon social groups were fed ad libitum (control, CTR) or 70% CTR (MNR) from 0.16 to 0.9G when fetuses were delivered by caesarean section under general anaesthesia. Plasma cortisol was elevated in fetuses of MNR mothers (P < 0.05). Immunoreactive PEPCK1 protein was located around the liver lobule central vein and was low in CTR fetuses but rose to 63% of adult levels in MNR fetuses. PCK1 mRNA measured by QRT-PCR increased in MNR (2.3-fold; P < 0.05) while the 25% rise in protein by Western blot analysis was not significant. PCK1 promoter methylation analysis using bisulfite sequencing was significantly reduced in six out of nine CpG-dinucleotides evaluated in MNR compared with CTR liver samples. In conclusion, these are the first data from a fetal non-human primate indicating hypomethylation of the PCK1 promoter in the liver following moderate maternal nutrient reduction.
Nijland
Mark J
MJ
Center for Pregnancy and Newborn Research, University of Texas Health Science Center, San Antonio, TX, USA.
Mitsuya
Kozoh
K
Li
Cun
C
Ford
Stephen
S
McDonald
Thomas J
TJ
Nathanielsz
Peter W
PW
Cox
Laura A
LA
D000818:Animals; D001483:Base Sequence; D044127:Epigenesis, Genetic / Q000235:genetics / Q000502:physiology*; D005260:Female; D005333:Fetus / Q000378:metabolism*; D008099:Liver / Q000196:embryology* / Q000201:enzymology*; D044342:Malnutrition / Q000378:metabolism*; D008745:Methylation; D023421:Models, Animal; D008969:Molecular Sequence Data; D010215:Papio / Q000378:metabolism*; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism
D012333:RNA, Messenger; D010729:Phosphoenolpyruvate Carboxykinase (GTP)