title: Methyl donor deficiency affects fetal programming of gastric ghrelin cell organization and function in the rat.
abstract: Methyl donor deficiency (MDD) during pregnancy influences intrauterine development. Ghrelin is expressed in the stomach of fetuses and influences fetal growth, but MDD influence on gastric ghrelin is unknown. We examined the gastric ghrelin system in MDD-induced intrauterine growth retardation. By using specific markers and approaches (such as periodic acid-Schiff, bromodeoxyuridine, homocysteine, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling, immunostaining, reverse transcription-polymerase chain reaction), we studied the gastric oxyntic mucosa cellular organization and ghrelin gene expression in the mucosa in 20-day-old fetuses and weanling pups, and plasma ghrelin concentration in weanling rat pups of dams either normally fed or deprived of choline, folate, vitamin B6, and vitamin B12 during gestation and suckling periods. MDD fetuses weighed less than controls; the weight deficit reached 57% at weaning (P < 0.001). Both at the end of gestation and at weaning, they presented with an aberrant gastric oxyntic mucosa formation with loss of cell polarity, anarchic cell migration, abnormal progenitor differentiation, apoptosis, and signs of surface layer erosion. Ghrelin cells were abnormally located in the pit region of oxyntic glands. At weaning, plasma ghrelin levels were decreased (-28%; P < 0.001) despite unchanged mRNA expression in the stomach. This decrease was associated with lower body weight. Taken together, these data indicate that one mechanism through which MDD influences fetal programming is the remodeling of gastric cellular organization, leading to dysfunction of the ghrelin system and dramatic effects on growth.
authors: INSERM U954, Nutrition, Génétique et Expositions aux Risques Environnementaux, 54505 Vandoeuvre Cedex, France.
authors: Carine
authors: C
authors: Bossenmeyer-Pourié
authors: Sébastien
authors: S
authors: Blaise
authors: Grégory
authors: G
authors: Pourié
authors: Catherine
authors: C
authors: Tomasetto
authors: Sandra
authors: S
authors: Audonnet
authors: Sandrine
authors: S
authors: Ortiou
authors: Violette
authors: V
authors: Koziel
authors: Marie-Christine
authors: MC
authors: Rio
authors: Jean-Luc
authors: JL
authors: Daval
authors: Jean-Louis
authors: JL
authors: Guéant
authors: Bernard
authors: B
authors: Beck
mesh_terms: D000818:Animals; D001835:Body Weight; D019070:Cell Lineage; D002794:Choline / Q000378:metabolism; D003677:Deficiency Diseases / Q000196:embryology* / Q000503:physiopathology*; D019858:Enteroendocrine Cells / Q000378:metabolism; D005260:Female; D047109:Fetal Development; D005492:Folic Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism* / Q000473:pathology*; D054439:Ghrelin / Q000097:blood / Q000378:metabolism*; D013006:Growth Hormone / Q000097:blood; D006710:Homocysteine / Q000097:blood; D007150:Immunohistochemistry; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D014805:Vitamin B 12 / Q000378:metabolism; D014886:Weaning
chemical_list: D054439:Ghrelin; D006710:Homocysteine; D013006:Growth Hormone; D005492:Folic Acid; D002794:Choline; D014805:Vitamin B 12