Lactation undernutrition leads to multigenerational molecular programming of hypothalamic gene networks controlling reproduction

Table 1 Significantly activated IPA BioFunctions identified for DEG in hypothalamus of CON vs LUN 21-day old female progeny (F1)

Categories	Functions annotation	p-value	Predicted activation state	Activation z-score^a	Bias-corrected z-score	Molecules*
Lipid metabolism, small molecule biochemistry	synthesis of lipid	0.00414	Increased	2.064	2.121	ACSL3, AGTR1, AVP, CCL2, CES1, CRHR2, DPP4, ESR1, FAS, FCGR1A, HSD3B1, KISS1, MARC2, MGST2, NR1H3, OXT, PIK3R1, POMC, PRKCD, PROX1, PTK2B, RGS3, TCF7L2, TRH
Connective tissue development and function, tissue morphology	mass of adipose tissue	0.00097	Decreased	−2.871	−2.857	CARTPT, CDKN1A, DLK1, E2F1, ESR1, FOXP2, HRH3, NR1H3, POMC, SHOX2
	quantity of connective tissue	0.00083	Decreased	−2.179	−2.161	ADAMTS1, Ahsp, CALCB, CARTPT, CCL2, CDKN1A, CES1, CHRNA7, CIDEB, CRHR2, E2F1, ESR1, HBA1/HBA2, Hbb-b1, HRH3, KLK3, NR1H3, PIK3R1, POMC, PRKG1, SLC14A1, SLC4A1, UHRF1
Cell cycle	cell cycle progression	0.00057	Decreased	−2.319	−2.289	ADARB1, AVP, CALCB, CAMK2A, CCK, CDKN1A, DPP4, E2F1, ESR1, FAS, HSPA1A/HSPA1B, ING3, LEF1, MCM2, MYOCD, NKX3-1, NUPR1, NUSAP1, PGAM2, PIK3R1, PRKCD, PRKCG, PRKCH, PRKG1, PROX1, PTK2B, PTPRN2, RASSF3, RBM3, TCF7L2, TF, USP1, USP2, VAV3, ZIC1
Cell-to-cell signaling and interaction	synaptic depression	0.00017	Decreased	−2.200	−2.171	ADCY1, CAMK2A, CPEB3, DLG4, GRID2IP, MAP1B, PRKCG, PTK2B, SV2B

^aThreshold for activation z- score for decreased BioFunctions was maintained at ≤ −2.179
*Genes up- (bold) and down-regulated in hypothalami of control (CON) vs. LUN 21-day old F1 females

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