title: Protein deficiency and intestinal nematode infection in pregnant mice differentially impact fetal growth through specific stress hormones, growth factors, and cytokines.
abstract: BACKGROUND
  Protein deficiency (PD) and intestinal nematode infections commonly co-occur during pregnancy and impair fetal growth, but the complex network of signals has not been explored.
  
  
  OBJECTIVE
  Our objective was to assess those stress hormones, growth factors, and cytokines affected by maternal PD and nematode infection and associated with fetal growth.
  
  
  METHODS
  Using a 2 × 2 factorial design, CD-1 mice, fed protein-sufficient (PS; 24%) or protein-deficient (PD; 6%) isoenergetic diets, were either uninfected or infected every 5 d with Heligmosomoides bakeri, beginning on gestational day (GD) 5. Biomarker concentrations were measured on GD 18 in maternal serum (m), fetal serum (f), and amniotic fluid (af) by using Luminex.
  
  
  RESULTS
  Maternal PD lowered fetal body mass (PS/uninfected 1.25 ± 0.02 g, PS/infected 1.19 ± 0.02 g vs. PD/uninfected 1.11 ± 0.02 g, PD/infected 0.97 ± 0.02 g; P = 0.02), fetal lung (P = 0.005), and liver (P = 0.003) but not brain mass, whereas maternal infection lowered fetal length (PS/uninfected 2.28 ± 0.02 cm, PD/uninfected 2.27 ± 0.03 cm vs. PS/infected 2.21 ± 0.03 cm, PD/infected 2.11 ± 0.02 cm; P = 0.05) and kidney mass (P = 0.04). PD elevated stress hormones (m-adrenocortiotropic hormone, f-corticosterone, af-corticosterone) and reduced insulin-like growth factor 1 in all compartments (P ≤ 0.01), but these were unassociated with fetal mass or length. Fetal mass was positively associated with f-leptin (R(2) = 0.71, P = 0.0001) and negatively with fetal cytokines [tumor necrosis factor-α: R(2) = 0.62, P = 0.001; interleukin-4 (IL-4): R(2) = 0.63, P = 0.0004]. In contrast, maternal infection lowered f-prolactin (P = 0.02) that was positively associated with fetal length (R(2) = 0.43; P = 0.03); no other biomarker was affected by infection. Regression analyses showed associations between organ growth, cytokines, and growth factors: 1) thymus, spleen, heart, and brain with m-IL-10; 2) brain and kidney with f-vascular endothelial growth factor, af-monocyte chemotactic protein 1, af-interferon-γ, and af-eotaxin; and 3) liver and lung with f-leptin and af-corticosterone (all P ≤ 0.02).
  
  
  CONCLUSIONS
  PD and nematode infection impaired fetal mass and linear growth, respectively. Fetal mass, length, and individual organ masses were regulated by different hormones, growth factors, and cytokines.
authors.affiliation: Institute of Parasitology, and.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Starr
authors.affiliation: Institute of Parasitology, and.
authors.forename: Marilyn E
authors.initials: ME
authors.lastname: Scott
authors.affiliation: School of Dietetics and Human Nutrition, McGill University (Macdonald Campus), Ste-Anne-de-Bellevue, Canada kris.koski@mcgill.ca.
authors.forename: Kristine G
authors.initials: KG
authors.lastname: Koski
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000032:analysis / Q000097:blood / Q000378:metabolism; D000653:Amniotic Fluid / Q000737:chemistry; D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D003345:Corticosterone / Q000032:analysis / Q000097:blood / Q000378:metabolism; D016207:Cytokines / Q000032:analysis / Q000097:blood / Q000378:metabolism; D005260:Female; D047109:Fetal Development / Q000502:physiology*; D005325:Fetal Organ Maturity; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis / Q000097:blood / Q000378:metabolism; D007411:Intestinal Diseases, Parasitic / Q000150:complications* / Q000378:metabolism; D051379:Mice; D009349:Nematode Infections / Q000150:complications* / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism; D011488:Protein Deficiency / Q000150:complications* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000097:blood
chemical_list: D015415:Biomarkers; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D042461:Vascular Endothelial Growth Factor A; D007334:Insulin-Like Growth Factor I; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone
keywords: Heligmosomoides bakeri; amniotic fluid; inflammation; mouse model; nematode; organ masses; protein deficiency; serum