Placental and Cord Blood Methylation of Genes Involved in Energy Homeostasis: Association With Fetal Growth and Neonatal Body Composition

Abstract

Low weight at birth is associated with subsequent susceptibility to diabetes. Epigenetic modulation is among the mechanisms potentially mediating this association. We performed a genome-wide DNA methylation analysis in placentas from term infants born appropriatefor-gestational-age (AGA) or small-for-gestational-age (SGA) to identify new genes related to fetal growth and neonatal body composition. Candidate genes were validated by bisulfite pyrosequencing (30 AGA, 21 SGA) and also analyzed in cord blood. Gene expression analyses were performed by RT-PCR. Neonatal body composition was assessed by dual X-ray absorptiometry at age 2 weeks. The ATG2B, NKX6.1, and SLC13A5 genes (respectively related to autophagy, b-cell development and function, and lipid metabolism) were hypermethylated in placenta and cord blood from SGA newborns, whereas GPR120 (related to free fatty acid regulation) was hypomethylated in placenta and hypermethylated in cord blood. Gene expression levels were opposite to methylation status, and both correlated with birth weight, circulating IGF-I, and total and abdominal fat at age 2 weeks. In conclusion, alterations in methylation and expression of genes involved in the regulation of energy homeostasis were found to relate to fetal growth and neonatal body composition and thus may be among the early mechanisms modulating later susceptibility to diabetes.

The sequence of prenatal growth restraint and postnatal catch‐up growth: normal heart but thicker intima‐media and more pre‐peritoneal fat in late infancy

“…S1, flow chart). Specific inclusion criteria for the present study were birth at Hospital Sant Joan de Déu, Barcelona, after an uncomplicated, term (37–42 weeks), singleton pregnancy (no gestational diabetes, no maternal hypertension, no alcohol abuse, no drug addiction); birth weight Z ‐score between −1 and +1 for gestational age (AGA birth weight range, 2.9–3.8 kg) or Z ‐score below −2 for gestational age (SGA birthweight range, 1.9–2.6 kg) ; either exclusive breastfeeding or exclusive formula feeding for 4 months; spontaneous catch‐up in weight and height, defined as weight and height Z ‐score > −2.0 by age 1 year ; written, informed consent from at least one parent. The exclusion criteria were clinical evidence for syndromic or infectious aetiology of SGA, complications at birth (resuscitation or parenteral nutrition), systemic disease, acute illness and congenital malformations.…”

The Effect Gestational Diabetes has on DNA Methylation as Related to Fetal Development and the Outcomes of the Mother and Offspring

“…A number of studies have focused on the effects of GDM-induced DNA methylation on fetal growth and newborn weigh [8,[63][64][65][66][67][68] (Table 1). The majority of these studies have analyzed placental cord blood [8,[63][64][65] while two studied both cord blood and placental cotyledon tissue [66,67]. These studies shared the finding that restricted fetal growth and offspring weight correlated with changed DNA methylation patterns in genes associated with growth control such as POU2F1, PKHD1, NFE2, NHLH2, and AGTR2 [8].…”

BMP9 promotes osteogenic differentiation of SMSCs by activating the JNK/Smad2/3 signaling pathway

“…Mesenchymal stem cells (MSCs), with low immunogenicity and multidirectional differentiation potential, are regarded as ideal seed cells in tissue engineering . Over the past decades, MSCs have been obtained from different tissues, including the bone marrow, adipose tissue, umbilical cord blood, and placental tissue . Bone formation requires an increase in the number of osteoblasts, which can be derived from MSCs .…”

“…11 Over the past decades, MSCs have been obtained from different tissues, including the bone marrow, adipose tissue, umbilical cord blood, and placental tissue. 12,13 Bone formation requires an increase in the number of osteoblasts, which can be derived from MSCs. 14,15 However, proper selection of seed cells for bone formation remains a critical problem.…”