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Table 3 Pathways associated with neurodevelopment 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

 Signaling pathways regulating pluripotency of stem cellsb

25/139 (17.99)

Wnt10a, Fgfr1, Mapk12, Pax6, Smad1, Wnt5b, Wnt7b (hypermethylated), Isl1, Neurog1, Onecut1, Bmpr1b, Dvl3, Esrrb, Fgfr2, Igf1r, Jak2, Klf4, Lhx5, Nanog, Pcgf1, Smad2, Smad3, Tbx3, Wnt3, Wnt7a (hypomethylated)

1.05E−03

 Autophagy—animalb

23/134 (17.16)

Bnip3, Mtmr4, Rraga (hypermethylated), Irs2, Irs3, Nrbf2, Pten, Rb1cc1, Rragd, Ulk2, Atg10, Bad, Ddit4, Eif2ak3, Ern1, Igf1r, Irs1, Lamp1, Ppp2cb, Prkaa1, Stk11, Stx17, Uvrag (hypomethylated)

3.07E−03

 Tight junctionb

25/170 (14.71)

Nedd4l, Actb, Arhgap17, Cldn18, Dlg2, Marveld3, Mpp4, Myh7b, Myl9, Prkag1, Prkci, Rapgef6 (hypermethylated), Cacna1d, Cldn17, Ezr, Itgb1, Slc9a3r1, Crb3, F11r, Hspa4, Marveld2, Ppp2cb, Prkaa1, Prkag2, Stk11 (hypomethylated)

1.54E−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

 Notch signaling pathway

10/52 (19.23)

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

 Protein processing in endoplasmic reticulum

23/164 (14.02)

Bag1, Ddit3, Dnajc5b, Gcs1, Hsph1, Nploc4, Preb, Stt3a (hypermethylated), Ckap4, Derl1, Dnaja2, Eif2ak3, Ern1, P4hb, Rad23b, Sec31a, Sec61a1, Sec61a2, Ssr1, Stt3b, Stub1, Ubqln1, Yod1 (hypomethylated)

3.23E−02

FA-S/FA-N

 Signaling pathways regulating pluripotency of stem cellsb

18/139 (12.95)

Neurog1, Dusp9, Hnf1a, Hras, Inhbb, Inhbe, Mapk3, Myc, Nodal, Pcgf3, Pcgf5, Zic3 (hypermethylated), Isl1, Onecut1, Wnt10a, Bmpr2, Fzd4, Map2k2 (hypomethylated)

8.27E−03

 Autophagy—animalb

18/134 (13.43)

Irs2, Pten, Rb1cc1, Atg2a, Atg3, Hras, Mapk3, Rps6kb1, RragB (hypermethylated), Irs3, Nrbf2, Rragd, Ulk2, Atg9b, Eif2s1, Gabarapl2, Map2k2, Rps6kb2 (hypomethylated)

5.67E−03

 Tight junctionb

21/170 (12.35)

Cldn17, Itgb1, Actr3b, Bves, Sympk, Tuba3b, Tuba4a (hypermethylated), Cacna1d, Ezr, Nedd4l, Slc9a3r1,Cldn11, Cldn19, Cttn, Gata4, Map3k1, Myl2, Ppp2r1b, Prkag3, Prkce, Synpo (hypomethylated)

7.82E−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

 TGF-beta signaling pathway

13/87 (14.94)

Cdkn2b, Fst, Inhbb, Inhbe, Ltbp1, Mapk3, Myc, Nodal, Rps6kb1 (hypermethylated), Bmpr2, Ppp2r1b, Rps6kb2, Tgfb1 (hypomethylated)

7.30E−03

 Axon guidance

19/178 (10.67)

Camk2a, Cfl1, Dpysl5, Hras, Itgb1, Mapk3, Nfatc4, Pak6, Plxnb3, Ppp3r2, Rac2, Sema4a, Sema7a, Trpc3 (hypermethylated), Bmpr2, Camk2d, Ntng1, Rgs3, Srgap2 (hypomethylated)

4.35E−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