Table 1.
Studies showing parallels in IUGR fetal pathology between sheep and humans
| Pathology | Sheep | Human | ||
|---|---|---|---|---|
| O2 | ~28% ↓ fetal arterial O2 at 0.7 gestation; 30–50% ↓ fetal arterial O2 near term | Limesand et al., 2007; Limesand et al., 2013; Macko et al., 2013; Macko et al., 2016 | ~33% ↓ fetal arterial O2 at ~0.75 gestation;15–40% ↓ cord blood O2 at delivery | Pardi et al., 1993; Roberts et al., 1999; Marconi et al., 2006 |
| Glucose | ~23% ↓ fetal arterial O2 at 0.7 gestation; ~40% ↓ fetal arterial O2 near term | Limesand et al., 2013; Macko et al., 2013; Macko et al., 2016 | ~33% ↓ umbilical vein glucose in 3rd trimester; ~50% ↓ cord blood glucose at delivery | Economides et al., 1991; Roberts et al., 1999; Lee et al., 2010 |
| Catecholamines | 5 to 5.7-fold ↑ fetal arterial norepinephrine near term; ~2.7-fold ↑ fetal arterial epinephrine near term | Limesand et al., 2007; Leos et al., 2010; Macko et al., 2013; Macko et al., 2016; Rozance et al., 2018 | 7.4-fold ↑ fetal arterial norepinephrine near term; 3.1-fold ↑ amniotic fluid norepinephrine in third trimester | Divers et al., 1981; Greenough et al., 1990 |
| Inflammation | 5-fold ↑ fetal arterial IL-6 near term; 10-fold ↑ fetal arterial Activin A near term | Bertucci et al., 2011; Kelly et al., 2017; Jones et al., 2018 | 1.3 to 2.4-fold ↑ cord blood TNFα, IL-6, and IL-18 at delivery | Makikallio et al., 2012; Krajewski et al., 2014; Visentin et al., 2014 |
| Insulin, IGF | ~40% (basal) and 52% (glucose-stim.) ↓ fetal arterial insulin near term; ~33% ↓ fetal arterial IGF-I near term | Bauer et al., 2003; Leos et al., 2010; Macko et al., 2016 | ~50% ↓ cord blood insulin at delivery; ~38% ↓ cord blood IGF-I at delivery; ~13% ↓ cord blood insulin at delivery | Hubinont et al., 1991; Lee et al., 2010 |
| Insulin action | 1.6 to 2.4-fold ↑ perinatal insulin sensitivity; ~19% ↓ neonatal insulin sensitivity | Camacho et al., 2016a; Camacho et al., 2017; Merrick et al., 2017 | 3.7-fold ↑ perinatal insulin sensitivity; ~7% ↓ insulin responsive in neonatal muscle | Ozanne et al., 2005; Meral et al., 2011; Milovanovic et al., 2014 |
| Glucose oxidation | 17–30% ↓ fetal glucose oxidation near term; ~33% ↓ neonatal glucose oxidation | Limesand et al., 2007; Brown et al., 2015; Merrick et al., 2017 | ~23% ↓ juvenile glucose oxidation | Jornayvaz et al., 2004 |
| Myoblast function | ~13% ↓ fetal myoblast proliferation; ~46% ↓ fetal myoblast differentiation; ~12% ↓ neonatal myoblast proliferation | Yates et al., 2014; Camacho et al., 2016b; Riley et al., 2016 | ↓ Myonuclear content of gastrocnemius muscle | Widdowson et al., 1972 |
IGF, insulin-like growth factor; IL, interleukin; IUGR, intrauterine growth restriction; TNFα, tumor necrosis factor α.