Both Genders Can Propagate Obesity-Prone-Phenotype Impacting Placental Amino Acid Transport System A Activity in a Rat Model of Gestational Protein Restriction
Article
Haafiz, Allah, Bernstein, Hilton M., Beveridge, Mark, Novak, Donald A.
funding text
This work was supported by NIH grants RO1 HD 29934 and HD 41112. Allah Haafiz and Hilton Bernstein contributed equally to this work, and should be considered co-first authors.
abstract
Background. Gestational protein restriction (GPR) can program a fetal phenotype prone to develop metabolic syndrome (MetS) in successive generations. Objectives. To understand the placental-fetal adaptations underpinning metabolic syndrome (MetS) prone phenotype in successive generations. Material and Methods. Rats (F0) were pair-fed either a 19% normal protein diet (NPD) or an 8% low protein diet (LPD) through pregnancy and lactation. Male and female offspring (F1) were bred to control animals, and the growth of F2 animals monitored for 15 months. [(14)C]-2-(methylamino) isobutyric acid) (MeAIB) was used to monitor the activity of placental amino acid transport system A (SysA). Results. Maternal weight gain (g) in F0 pregnancies of the LPD group was less than the NPD group (105 +/- 15 vs. 120 +/- 25, p <= 0.005). Fetal, 3.8 +/- 0.9 g (LPD) vs. 3.7 +/- 0.7 g (NPD); p <= 0.2, and placental weights, 0.56 +/- 0.01 g (LPD) vs. 0.6 +/- 0.02 g (NPD); p <= 0.6 were comparable. MeAIB transfer expressed as (DPM) of gram fetus/mL maternal serum (0.08 +/- 0.010 vs. 0.14 +/- 0.02; p <= 0.003) and (DPM) gram fetus/DPM gram placenta were lower (0.10 +/- 0.01 vs. 0.14 +/- 0.01; p <= 0.02) in LPD than NPD group. Transport in apical membrane vesicles from LPD group was decreased (15 +/- 2 vs. 23 +/- 4, pmol.mg(-1) protein 10sec(-1); p = 0.05). Maternal-fetal MeAIB transfers, fetal and placental weights, and maternal weight gains in F1 pregnancies were comparable between animals descended from NPD and LPD groups. However, F2 generation postnatal weight gains were impacted by F1 gestational nutrition (LPD vs. NPD; p <= 0.0001). Conclusions. Moderate GPR impacted placental nutrient transfer in F0 pregnancies; F2 descended from LPD exposed F1 generation tended to be larger than their NPD derived counterparts through 15 months of age samples (Adv Clin Exp Med 2010, 19, 3, 301-312).