Maternal low protein diet restricted to the preimplantation period induces a gender-specific change on hepatic gene expression in rat fetuses.

It has been shown previously that maternal low protein diet (LPD) throughout rat gestation altered hepatic gene expression and enzyme activities in offspring. Here, we investigate the effect of maternal LPD (9% casein vs. 18% control) exclusively during the preimplantation period (switched diet group) or provided throughout gestation on hepatic gene expression in day 20 fetuses. Using quantitative competitive PCR, we found that switched diet induced a two-fold increase (P = 0.008) in hepatic gene expression of phosphoenolpyruvate carboxykinase (PEPCK, a rate limiting enzyme for gluconeogenesis) in male fetuses and a 17% increase (P = 0.005) in 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1, acts primarily as a reductase to produce active glucocorticoid) in female liver compared with control fetuses. Maternal LPD administered throughout gestation increased 11beta-HSD1 expression in male fetal liver by 27% (P = 0.042) compared with controls. However, maternal LPD fed for either period did not affect fetal hepatic insulin receptor (IR), glucocorticoid receptor (GR), glycogen synthase (GS) nor placental glucose transporter 1 (Glut1) and 3 (Glut3) transcript levels. The alteration in fetal hepatic gene expression could not be attributed specifically to known regulators including insulin or glucose concentrations in fetal blood nor alteration in cAMP in fetal liver, although a combination of these regulatory factors may be responsible. Fetal hepatic glycogen level was unaffected by maternal diet. The present findings show that the long term potential of the preimplantation embryo is sensitive to maternal LPD such that basal levels of hepatic gene expression in day 20 fetuses are altered in a gender-specific manner.

Imprinted gene expression in the rat embryo-fetal axis is altered in response to periconceptional maternal low protein diet.

In our previous study, we have shown that maternal low protein diet (LPD, 9% casein vs 18% casein control) fed exclusively during the rat preimplantation period (0-4.25 day postcoitum) induced low birth weight, altered postnatal growth and hypertension in a gender-specific manner. In this study, we investigated the effect of maternal LPD restricted only to the preimplantation period (switched diet) or provided throughout gestation on fetal growth and imprinted gene expression in blastocyst and fetal stages of development. Male, but not female, blastocysts collected from LPD dams displayed a significant reduction (30%) in H19 mRNA level. A significant reduction in H19 (9.4%) and Igf2 (10.9%) mRNA was also observed in male, but not in female, fetal liver at day 20 postcoitum in response to maternal LPD restricted to the preimplantation period. No effect on the blastocyst expression of Igf2R was observed in relation to maternal diet. The reduction in H19 mRNA expression did not correlate with an observed alteration in DNA methylation at the H19 differentially methylated region in fetal liver. In contrast, maternal LPD throughout 20 days of gestation did not affect male or female H19 and Igf2 imprinted gene expression in fetal liver. Neither LPD nor switched diet treatments affected H19 and Igf2 imprinted gene expression in day 20 placenta. Our findings demonstrate that one contributor to the alteration in postnatal growth induced by periconceptional maternal LPD may derive from a gender-specific programming of imprinted gene expression originating within the preimplantation embryo itself.