Epigenetic modifications of placenta in women with gestational diabetes mellitus and their offspring

Table 1 Relationship between placental transport function and fetal weight in gestational diabetes mellitus

Nutrient	Transporter	GDM model		Cell lines	Mechanism of action	Localization	Result	Ref.
		Gestational age	Animal species
Glucose	GLUT1	37+ wk gestation	-	-	-	P↑; BM↑	FBW (+); AFM (+), SSFM (+)	[17,18]
		Full-term placenta	-	-	p-Akt and Erk↑	P↑	FBW↑	[23]
	GLUT4	37+ wk gestation	-	-	-	P↑	SSFM (+); FBW (+)	[17]
	GLUT9	37+ wk gestation	-	-	-	P↑	FBW (*)	[17]
	GLUT3	-	db/+mice & HFD-induced C57B L/6J mice	-	AMPK↓	PM↓	FBW↑	[20]
Amino acids	System A	-	-	Insulin stimulates PHT cell and PVE	p-Akt and Erk↑	PHT↑	FBW↑	[9]
		-	-	TNF-α stimulation PHT cell	Erk; p38MAPK	PHT↑	FBW↑	[30]
		-	-	IL-6 treat PCT	JAK/STAT	PCT↑	FBW↑	[31]
		-	-	LPS and poly (I:C) treat PCT	TLR3 and TLR4↑	PCT↑	FBW↑	[32]
	SNAT 1	37-41+6 wk gestation	-	-	IGF-I and mTOR↑	P↑	FBW (+)	[25]
		-	-	TNF-α stimulation PHT cell	Erk; p38MAPK	PHT↑	FBW↑	[30]
		-	-	LPS and poly (I:C) treat PCT	TLR3 and TLR4↑	PCT↑	FBW↑	[32]
	SNAT2	-	-	TNF-α stimulation PHT cell	Erk; p38MAPK	PHT↑	FBW↑	[30]
		-	-	IL-6 treat PCT	JAK/STAT	PCT↑	FBW↑	[31]
		-	-	LPS and poly (I:C) treat PCT	TLR3 and TLR4↑	PCT↑	FBW↑	[32]
	SNAT3	-	-	IL-6 treat PCT	JAK/STAT	PCT↑	FBW↑	[31]
	System L	-	-	MVM and BMs from GDM	-	MVM↑	FBW↑	[28]
		-	STZ-induced SD rats	-	mTORC1↓	P↓	FBW↓	[46]
Lipids	TG	-	-	Hight glucose and insulin treat PHT	-	PHT↑	FBW↑	[35]
		-	HF/HCD induced C57BL/6J mice	-	CEH↑, TGH↓	P↑	FBW↑	[36]
		37-42 wk gestation	-	Hight glucose treat PE	β-oxidation↓	P↑	FBW↑	[38]
	EL	Full-term placenta	-	-	p-Akt and Erk↑	P↑	FBW↑	[41]
	FAT	-	-	Hight glucose and insulin treat PHT	-	PHT↑	FBW↑	[35]
		Full-term placenta	-	-	p-Akt and Erk↑	P↑	FBW↑, FBW (+)	[41,42]
	FABP4 A-FABP L-FABP	Full-term placenta	-	-	p-Akt and Erk↑	PHT↑, P↑	FBW↑	[34,40,41]
	FABP3, FABP4	-	-	Hight glucose and insulin treat PHT	-	PHT↑	FBW↑	[35]
	FATP-1	Full-term placenta	-	-	p-Akt and Erk↑	P↑	FBW↑	[41]

P: Placenta; FBW: Fetal baby weight; SSFM: Subscapular fat mass; AFM: Abdominal; PM: Plasma membrane; BM: Basement membrane; PHT: Primary human trophoblast; PVE: Placental villous explants; PE: Placental explants; PTC: Primary trophoblast cells; CEH: Cholesterol ester hydrolase; MVMs: Microvillous plasma membranes; +: Positive correlation; *: Correlation; FATPs: Fatty acids transport proteins.