Ovine Surgical Model of Uterine Space Restriction: Interactive Effects of Uterine Anomalies and Multifetal Gestations on Fetal and Placental Growth1

Abstract

Intrauterine growth restriction (IUGR) is observed in conditions with limitations in uterine space (e.g., uterine anomalies and multifetal gestations). IUGR is associated with reduced fetal weight, organ growth, and a spectrum of adult-onset diseases. To examine the interaction of uterine anomalies and multifetal gestations, we developed a surgical uterine space restriction model with a unilateral uterine horn ligation before breeding (unilateral surgery). Placentas and fetuses were studied on Gestational Day (GD) 120 and GD 130 (term = 147 days). Unilateral surgery decreased placentome numbers in singleton and twin pregnancies (25% and 50%, respectively) but not unilateral triplets. Unilateral surgery decreased total placentome weight in twin pregnancies (decreased 24%). Fetuses categorized as uterine space restricted (unilateral twin and both groups of triplets) had 51% fewer placentomes per fetus and a 31% reduction in placentomal weight per fetus compared to the nonrestricted group (control singleton, unilateral singleton, and control twin). By GD 130, uterine space-restricted fetuses exhibited decreased weight, smaller crown-rump, abdominal girth, and thoracic girth as well as decreased fetal heart, kidney, liver, spleen, and thymus weights. Lung and brain weights were unaffected, demonstrating asymmetric IUGR. At GD 130, placental efficiency (fetal weight per total placentomal weight) was elevated in uterine space-restricted fetuses. However, fetal arterial creatinine, blood urea nitrogen, and cholesterol were elevated, suggesting insufficient placental clearance. Maternal-to-fetal glucose and triglycerides ratios were elevated in the uterine space-restricted pregnancies, suggesting placental nutrient transport insufficiency. This model allows for examination of interactive effects of uterine space restriction-induced IUGR on placental adaptation and fetal organ growth.

Impact of chronic hypoxemia on blood flow to the brain, heart, and adrenal gland in the late-gestation IUGR sheep fetus

“…Interestingly, there was an increase in placental efficiency (i.e., fetal:placental weight) in the PR fetuses. This is consistent with a model of IUGR, in which uterine space is restricted, and this is associated with a higher placental efficiency (51). This suggests that adaptations occur in the placenta of PR fetuses that increase the ability of the placenta to transfer substrates to the PR fetus or that the PR fetus makes adaptations such that the requirement for substrates is reduced.…”

Uterine artery leptin receptors during the ovarian cycle and pregnancy regulate angiogenesis in ovine uterine artery endothelial cells†

“…This model restricts pregnancy to only one horn (gravid) throughout gestation allowing us to study local pregnancy-specific maternal-fetal vascular function and angiogenesis [25][26][27]. The control pregnant group comprised of sham operated (n = 15) and nonsurgical controls (n = 22).…”

“…During pregnancy, these uterine vascular adaptations lead to the rises in UBF which are required to provide for an adequate maternal-fetal vascular interface to meet the nutrient and oxygen demands of the rapidly growing fetus [21]. Using a preconception surgical model, we established a cohort of unilateral ovine pregnancies and demonstrated that rises in UBF as well as uterine vascular adaptations are seen only ipsilateral, but not contralateral, to the fetus and placental unit [25][26][27]. Additionally, we previously reported experimental analyses of the ex vivo uterine artery endothelium (UAendo) and uterine artery vascular smooth muscle (UAvsm) from pregnant versus nonpregnant ewes.…”

Growth and development of the ovine conceptus1

“…However, there are also many nonfunctional caruncles (i.e., those that did not participate in induction of formation of a placentome). The number of functional caruncles and placentomes can be altered surgically (Alexander, 1964a) or by restricting the pregnancy to 1 uterine horn (Bazer et al, 1979), but there is compensatory growth of placentomes so that fetal weight is not necessarily affected (Meyer et al, 2010). In fact, we used the unilaterally pregnant ewe model to test the hypothesis that intrauterine crowding would stimulate more caruncles to become engaged with the chorioallantos to form placentomes (Bazer et al, 1979;Gaton et al, 1984).…”