The intrauterine metabolic environment modulates the gene expression pattern in fetal rat islets: prevention by maternal taurine supplementation.
OBJECTIVE
Events during fetal life may in critical time windows programme tissue development leading to organ dysfunction with potentially harmful consequences in adulthood such as diabetes. In rats, the beta cell mass of progeny from dams fed with a low-protein (LP) diet during gestation is decreased at birth and metabolic perturbation lasts through adulthood even though a normal diet is given after birth or after weaning. Maternal and fetal plasma taurine levels are suboptimal. Maternal taurine supplementation prevents these induced abnormalities. In this study, we aimed to reveal changes in gene expression in fetal islets affected by the LP diet and how taurine may prevent these changes.


METHODS
Pregnant Wistar rats were fed an LP diet (8% [wt/wt] protein) supplemented or not with taurine in the drinking water or a control diet (20% [wt/wt] protein). At 21.5 days of gestation, fetal pancreases were removed, digested and cultured for 7 days. Neoformed islets were collected and transcriptome analysis was performed.


RESULTS
Maternal LP diet significantly changed the expression of more than 10% of the genes. Tricarboxylic acid cycle and ATP production were highly targeted, but so too were cell proliferation and defence. Maternal taurine supplementation normalised the expression of all altered genes.


CONCLUSIONS
Development of the beta cells and particularly their respiration is modulated by the intrauterine environment, which may epigenetically modify expression of the genome and programme the beta cell towards a pre-diabetic phenotype. This mis-programming by maternal LP diet was prevented by early taurine intervention.
Reusens
B
B
Laboratoire de Biologie Cellulaire, Université catholique de Louvain, 5, Place Croix du Sud, 1348, Louvain-la-Neuve, Belgium. brigitte.reusens@uclouvain.be
Sparre
T
T
Kalbe
L
L
Bouckenooghe
T
T
Theys
N
N
Kruhøffer
M
M
Orntoft
T F
TF
Nerup
J
J
Remacle
C
C
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D019587:Dietary Supplements; D005260:Female; D005333:Fetus / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D006019:Glycolysis / Q000235:genetics; D050417:Insulin-Secreting Cells / Q000201:enzymology / Q000502:physiology; D007515:Islets of Langerhans / Q000196:embryology* / Q000201:enzymology / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D013654:Taurine / Q000097:blood / Q000494:pharmacology*; D014599:Uterus / Q000502:physiology
D013654:Taurine; D000255:Adenosine Triphosphate