Table 1.

Placenta-related phenotypes associated with genetic disruption of components of the HIF signaling pathway.

Gene symbol	Species	Mutationa	Placental phenotype	References
Arnt	Mouse	Global-LOF	Midgestation lethality (gd 9.5 to 10.5); failure of labyrinthine vascularization; decreased junctional zone trophoblast progenitor cells	Kozak et al., 1997; Maltepe et al., 1997; Abbott and Buckalew, 2000; Adelman et al., 2000
Hif1a	Mouse	Global-LOF	Midgestation lethality (gd 10.5); impaired labyrinthine vascularization; decreased junctional zone trophoblast progenitor cells; not as severe as Arnt null placenta phenotype	Iyer et al., 1998; Ryan et al., 1998; Kotch et al., 1999; Cowden-Dahl et al., 2005a
Hif1a	Mouse	Maternal-LOF	Placental growth restriction; disrupted decidual natural killer cell expansion and interstitial trophoblast invasion	Kenchegowda et al., 2017
Epas1	Mouse	Global-LOF	Modest placental phenotype	Cowden-Dahl et al., 2005a
Hif1a/Epas1	Mouse	Global-LOF	Phenocopies global Arnt null	Cowden-Dahl et al., 2005a
Egln1	Mouse	Global-LOF	Lethality between gd 12.5 and 14.5; junctional zone expansion and compromised labyrinth zone development	Takeda et al., 2006; Ozolins et al., 2009
Vhl	Mouse	Global-LOF	Midgestation lethality (gd 10.5 to 12.5); failure of labyrinthine vascularization	Gnarra et al., 1997
Fih1	Mouse	Global-LOF	None apparent	Zhang et al., 2010
Cited2	Mouse	Global-LOF	Placental growth restriction	Withington et al., 2006
Cited2	Rat	Global-LOF	Placental growth restriction	Dhakal et al., 2016
Cited2	Mouse	Trophoblast-LOF	Impaired labyrinthine vascularization	Moreau et al., 2014
Commd1	Mouse	Global-LOF	Midgestation lethality (gd 9.5 to 10.5); failure of labyrinthine vascularization	van de Sluis et al., 2007
miR-210	Mouse	Global-LOF	None apparent	Krawczynski et al., 2016
miR-210	Mouse	Trophoblast-GOF	None apparent	Krawczynski et al., 2016
Kdm3a	Rat	Trophoblast-LOF	Disruption of hypoxia-activated placenta adaptations	Chakraborty et al., 2016
Mmp12	Rat	Global-LOF	Disruption of hypoxia-activated placenta adaptations	Chakraborty et al., 2016

^aLOF, loss of function; GOF, gain of function