Poster Topical Area: Nutrient-Gene Interactions

Location: Hall D

Poster Board Number: 447

P17-024 - Imbalance in maternal dietary ratio of folate and vitamin B12 during pregnancy influences expression of imprinted IGF2/H19lncRNAvia epigenetic regulation

Sunday, Jun 10
8:00 AM – 6:00 PM

Objective:Till date there have been no studies to check the effect of altered dietary ratio of folate and vitamin B12 during pregnancy on fetal growth. So, the present study was designed to check the influence of dietary ratio of both vitamins on:


Abbreviations: NB: Normal B12 NF: Normal folate FD: Folate deficient FO: Folate over supplementation BD: B12 deficient BO: B12 over supplementation


Methods:
Four week old C57BL/6 female mice (F0) were randomized into nine groups NBNF, NBFO, NBFD, BDNF, BDFD, BDFO, BONF, BOFO and BOFDand were fed diet (V khot et al.,2014) for six weeks while males were on normal diet. Mating was carried out and both male and female fetuses (F1) fed on the same diets were mated again and on day 20 of gestation maternal and fetal tissues (F2) were isolated. Folate, homocysteine and B12 levels were analyzed in serum. The expression of miRNA 675 and imprinted genes along with their promoter DNA methylation was studied. Expression of folate transporters RFC, PCFT, FOLR1 and global DNA methylation were studied.


Results:
Circulating folate, B12 levels were reduced while homocysteine levels were high in F1 females of deficient groups (P<0.01).Abnormal growth in fetuses was observed in both deficient conditions along with altered male/female ratio. In maternal and fetal tissues, over-expression of H19 was observed in deficient conditions along with decreased promoter methylation (P<0.01). Biparental expression of H19 in F2 fetuses was found in NBFD and BDFD groups in spite of being transcribed from the maternal allele.In contrast, loss of IGF2 was observed along with increased methylation in both F1 and F2 generation(P<0.05) in deficient groups. miRNA 675 associated with IGF2/H19 locus was upregulated in maternal tissues under deficient conditions.

Expression of folate transporters viz. PCFT, RFC and FOLR1 was increased in deficient groups (P<0.01) along with decrease in global methylation in maternal tissues except placenta (P<0.05)


Conclusion:
Maternal dietary ratio of folate and B12 during pregnancy influences fetal growth by altering the expression and promoter methylation of imprinted IGF2/H19lncRNA.




Funding Source: Department of Biotechnology (BT/PR10671/PFN/20/811/2013), Government of India
PGIMER, Chandigarh
Circulating folate, B12 and Homocysteine levels in serum of F1 generation

Body weights of mice for F1 generation and ratio of male/female born to F1 generation (mother)

CoAuthors: DIVIKA SAPEHIA, Ph.D Research Scholar – PGIMER; Dr. Jyotdeep Kaur, Ph.D – PGIMER

Aatish Mahajan

Ph.D Research Scholar
PGIMER, Chandigarh
Chandigarh, Chandigarh, India