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Table 4 Pathways associated with learning/memory abilities were differentially methylated in the brain of males in response to maternal FA intake during pregnancy

From: Maternal folic acid impacts DNA methylation profile in male rat offspring implicated in neurodevelopment and learning/memory abilities

Group/pathway

No. of DMGs (%)a

Selected genes

P value

FA-D/FA-N

 cGMP-PKG signaling pathwayb

29/167 (17.37)

Gucy1a2, Gucy1a3, Adcy4, Calml3, Ednra, Myh7, Myl9, Mylk2, Pde2a (hypermethylated), Adcy3, Adcy7, Cacna1d, Irs2, Irs3, Adcy1, Adcy5, Adrb1, Atp2b4, Bad, Gna11, Gna13, Irs1, Itpr3, Kcnmb4, Mrvi1, Pde2a, Pde3b, Pde5a, Ppp1ca, Vdac3 (hypomethylated)

7.83E−04

 Gap junctionb

15/88 (17.05)

Gucy1a2, Gucy1a3, Adcy4, Egfr (hypermethylated), Adcy3, Adcy7, Adcy1, Adcy5, Adrb1, Cdk1, Gna11, Itpr3, Pdgfc, Sos1, Tubb6 (hypomethylated)

1.61E−02

 Calcium signaling pathwayb

27/188 (14.36)

Grin2d, Adcy4, Calml3, Cckbr, Ednra, Egfr, Erbb3, Grin1, Mylk2, P2rx1, Ptger1, Tnnc2, Trhr (hypermethylated), Adcy3, Adcy7, Cacna1d, Cacna1h, Gnal, Phkg2, Adcy1, Adrb1, Atp2b4, Gna11, Itpr3, Plcd3, Stim2, Vdac3 (hypomethylated)

1.63E−02

 mTOR signaling pathway

26/157 (16.56)

Atp6v1f, Flcn, Rps6ka1, Rraga, Slc3a2, Wnt10a, Wnt5b, Wnt7b (hypermethylated), Atp6v1b2, Atp6v1e2, Atp6v1h, Cab39, Ddit4, Dvl3, Eif4e2, Igf1r, Irs1, Prkaa1, Pten, Rps6ka3, Rragd, Sos1, Stk11, Ulk2, Wnt3, Wnt7a (hypomethylated)

2.86E−03

 Rap1 signaling pathway

30/217 (13.82)

Actb, Adcy4, Calml3, Egfr, Fgf14, Fgf21, Fgfr1, Grin1, Mapk12, Prkci, Rapgef6, Skap1, Vegfb (hypermethylated), Adcy1, Adcy3, Adcy5, Adcy7, Efna2, Fgf12, Fgf20, Fgfr2, Igf1r, Itgb1, Kitlg, Map2k3, Ngfr, Pdgfc, Pfn1, Rasgrp3, Sipa1l2 (hypomethylated)

1.93E−02

 Notch signaling pathway

10/52 (19.23)

Aph1b, Notch1, Psen1 (hypermethylated), Ctbp2, Dtx3l, Dvl3, Hes5, Jag1, Lfng, Notch2 (hypomethylated)

2.09E−02

 Endocytosis

35/263 (13.31)

Ap2m1, Arpc4, Chmp1a, Chmp2a, Chmp5, Cyth2, Dnm3, Egfr, Folr1, Gbf1, Grk5, Iqsec3, Kif5a, Nedd4l, Prkci, RT1-M10-1, Sh3kbp1, Stam2, Stambp (hypermethylated), Arf1, Arf5, Arf6, Capza2, Cxcr4, Fgfr2, Git2, Igf1r, Pld2, Rab11fip1, Sh3glb2, Smad2, Smad3, Snx2, Spg20, Vps37a (hypomethylated)

2.09E−02

 Neurotrophin signaling pathway

19/124 (15.32)

Calml3, Irak3, Irak4, Kidins220, Mapk12, Ntf3, Ntrk1, Psen1, Rps6ka1, Tp73 (hypermethylated), Arhgdia, Bad, Irs1, Ngfr, Ntrk2, Ptpn11, Rela, Rps6ka3, Sos1 (hypomethylated)

2.17E−02

FA-S/FA-N

 cGMP-PKG signaling pathwayb

25/167 (14.97)

Adcy3, Adcy7, Gucy1a2, Irs2, Calm3, Cngb1, Mapk3, Nfatc4, Ppp3r2 (hypermethylated), Cacna1d, Gucy1a3, Irs3, Adcy2, Adcy6, Adra2c, Atp1b1, Atp1b3, Fxyd2, Gata4, Kcnma1, Map2k2, Mylk, Nos3, Prkce, Slc8a2 (hypomethylated)

2.38E−04

 Gap junctionb

14/88 (15.91)

Adcy3, Adcy7, Gucy1a2, Csnk1d, Hras, Htr2c, Mapk3, Mapk7, Tuba3b, Tuba4a (hypermethylated), Gucy1a3, Adcy2, Adcy6, Map2k2 (hypomethylated)

3.07E−03

 Calcium signaling pathwayb

27/188 (14.36)

Adcy3, Adcy7, Cacna1h, Phkg2, Calm3, Camk2a, Drd5, Grpr, Htr2c, P2rx4, P2rx6, Phka2, Ppp3r2, Tacr1 (hypermethylated), Cacna1d, Gnal, Grin2d, Adcy2, Camk2d, Erbb4, Gna14, Htr5b, Ltb4r2, Mylk, Nos3, P2rx5, Slc8a2 (hypomethylated)

2.73E−04

 MAPK signaling pathway

37/298 (12.42)

Cacna1h, Dusp4, Dusp8, Dusp9, Fgf16, Fgf4, Hras, Hspa8, Hspb1, Il1rap, Map4k3, Mapk3, Mapk7, Myc, Myd88, Pla2g4b, Ppp3r2, Rac2 (hypermethylated), Cacna1d, Cacng6, Cdc25b, Dusp3, Fas, Fgf20, Ikbkb, Il1r1, Kitlg, Map2k2, Map3k1, Map3k12, Map3k13, Map4k4, Mapk8ip1, Tgfa, Tgfb1, Traf2, Vegfa (hypomethylated)

4.51E−04

 ErbB signaling pathway

15/89 (16.85)

Camk2a, Hras, Mapk3, Myc, Pak6, Rps6kb1, Shc2 (hypermethylated), Areg, Camk2d, Erbb4, Map2k2, Rps6kb2, Shc1, Shc3, Tgfa (hypomethylated)

1.22E−03

 Glutamatergic synapse

14/116 (12.07)

Adcy3, Adcy7, Grm6, Mapk3, Pla2g4b, Ppp3r2, Slc17a8, Slc38a1 (hypermethylated), Adcy2, Adcy6, Cacna1d, Grin2d, Shank1, Shank2 (hypomethylated)

3.20E−02

 Neuroactive ligand-receptor interaction

29/291 (9.97)

Chrna2, Drd5, Gabra5, Gabrd, Gabre, Gcgr, Gpr50, Grm6, Grpr, Htr1a, Htr2c, P2rx4, P2rx6, Prss2, Pth1r, Sstr1, Tacr1, Uts2r (hypermethylated), Adra2c, Chrna1, Glp2r, Grid1, Grin2d, Htr5b, Ltb4r2, Mc2r, P2rx5, Prlhr, Ptgir (hypomethylated)

3.44E−02

  1. The genes which altered methylation in both FA-D and FA-S were showed by bold type. The P value was calculated by Fisher’s exact test
  2. aThe ratio of No. of DMGs was calculated by the number of DMGs in a given pathway divided by the total number of genes in this pathway
  3. bThe pathways overlapped between FA-D/FA-N and FA-S/FA-N groups