Abstract
Placental restriction and insufficiency are associated with altered patterns of placental growth, morphology, substrate transport capacity, growth factor expression, and glucocorticoid exposure. We have used a pregnant sheep model in which the intrauterine environment has been perturbed by uterine carunclectomy (Cx). This procedure results in early restriction of placental growth and either the development of chronic fetal hypoxemia (PaO2≤17 mmHg) in late gestation or in compensatory placental growth and the maintenance of fetal normoxemia (PaO2>17 mmHg). Based on fetal PaO2, Cx, and Control ewes were assigned to either a normoxemic fetal group (Nx) or a hypoxemic fetal group (Hx) in late gestation, resulting in 4 groups. Cx resulted in a decrease in the volumes of fetal and maternal connective tissues in the placenta and increased placental mRNA expression of IGF2, vascular endothelial growth factor (VEGF), VEGFR‐2,ANGPT2, and TIE2. There were reduced volumes of trophoblast, maternal epithelium, and maternal connective tissues in the placenta and a decrease in placental GLUT1 and 11βHSD2 mRNA expression in the Hx compared to Nx groups. Our data show that early restriction of placental growth has effects on morphological and functional characteristics of the placenta in late gestation, independent of whether the fetus becomes hypoxemic. Similarly, there is a distinct set of placental changes that are only present in fetuses that were hypoxemic in late gestation, independent of whether Cx occurred. Thus, we provide further understanding of the different placental cellular and molecular mechanisms that are present in early placental restriction and in the emergence of later placental insufficiency.
Highlights
In mammals, the placenta is the primary interface between the mother and fetus and plays an essential role in maintaining fetal growth and development by facilitating the transfer of oxygen and nutrients to the fetus and removing fetal carbon dioxide and wastes
Total placental weight was lower in the Cx compared with the Control groups (P < 0.05), and lower in the hypoxemic fetal group (Hx) compared with the normoxemic fetal group (Nx) groups (P < 0.05; Fig. 2), irrespective of the sex of the fetus
This study has shown that early restriction of placental growth affects morphological and functional characteristics of the placenta in late gestation, independently of whether or not the fetus becomes hypoxemic (Fig. 9)
Summary
The placenta is the primary interface between the mother and fetus and plays an essential role in maintaining fetal growth and development by facilitating the transfer of oxygen and nutrients to the fetus and removing fetal carbon dioxide and wastes. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society. Regulation of Placental Structure and Function placenta to deliver an adequate supply of substrates to the fetus is termed placental insufficiency and results in intrauterine growth restriction (IUGR). IUGR is clinically defined as a birth weight below the tenth centile for gestational age, that is, where the fetus does not meet its growth potential (McMillen et al 2001; Morrison 2008). IUGR affects 5–10% of pregnancies in developed countries (Limesand et al 2006; Bamfo and Odibo 2011; Li et al 2012), and is associated with a high incidence of perinatal morbidity and mortality, as well as an increased risk of cardiovascular disease, hypertension and type 2 diabetes in adulthood (Barker et al 1993, 2010; McMillen and Robinson 2005)
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