title: Maternal low protein diet restricted to the preimplantation period induces a gender-specific change on hepatic gene expression in rat fetuses.
abstract: 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.
authors.affiliation: School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton, UK. wyk@soton.ac.uk
authors.forename: Wing Yee
authors.initials: WY
authors.lastname: Kwong
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Miller
authors.forename: Adrian P
authors.initials: AP
authors.lastname: Wilkins
authors.forename: Mark S
authors.initials: MS
authors.lastname: Dear
authors.forename: J Neville
authors.initials: JN
authors.lastname: Wright
authors.forename: Clive
authors.initials: C
authors.lastname: Osmond
authors.forename: Junlong
authors.initials: J
authors.lastname: Zhang
authors.forename: Tom P
authors.initials: TP
authors.lastname: Fleming
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics; D000818:Animals; D001755:Blastocyst; D001786:Blood Glucose / Q000032:analysis; D000242:Cyclic AMP / Q000032:analysis; D018753:Diet, Protein-Restricted; D005260:Female; D005333:Fetus / Q000737:chemistry / Q000378:metabolism*; D015870:Gene Expression; D007328:Insulin / Q000097:blood; D008099:Liver / Q000737:chemistry / Q000378:metabolism*; D008112:Liver Glycogen / Q000097:blood; D008297:Male; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000235:genetics; D010920:Placenta / Q000737:chemistry / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012737:Sex Factors
chemical_list: D001786:Blood Glucose; D007328:Insulin; D008112:Liver Glycogen; D012333:RNA, Messenger; D000242:Cyclic AMP; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D019764:Phosphoenolpyruvate Carboxykinase (ATP)