Fetal Research

Intrauterine growth restriction (IUGR) is a major cause of perinatal morbidity, death, and longterm complications, such as diabetes and hypertension in adulthood. IUGR is associated with a reduced rate of net protein accretion. One PPB-funded research group is focused on increasing the rate of fetal growth by altering maternal amino-acid concentrations. This group already demonstrated that, in normal human pregnancies, maternal infusion of a commercial amino-acid solution elevates maternal amino-acid concentrations, which leads to significantly higher umbilical uptake of most amino acids. Their current research project has demonstrated that, in pregnancies complicated by IUGR, increasing the maternal concentration of amino acids leads to an increased fetal uptake of some amino acids. PPB researchers are continuing their studies of the development of IUGR (Am J Obstet Gynecol 2002; 187:741-6).

Locally expressed, vascular mediators that are of a paracrine nature regulate the uteroplacental vasculature. By studying these mediators, diseases related to inadequate uteroplacental perfusion, including IUGR and preeclampsia, can be better understood. One PPB-funded researcher has concentrated on endothelins, a family of potent, long-acting vasoconstrictors, and their role in perfusion. Specifically, this work explores endothelin-1 (ET-1), the most physiologically significant isoform in mammals that is produced by the vascular endothelium. This research has studied the role of ET-1 in the pathophysiology of hypoxia-induced IUGR in the rat model. By administering an endothelin-A receptor agonist to prevent hypoxia-induced IUGR, the grantee has elucidated the primary role of ET-1 in the development of growth restriction. An ET-1-mediated increase in vascular resistance in the uteroplacental vascular bed leads to decreased placental perfusion, which then leads to hypoxia and IUGR. A better understanding of the mechanisms that regulate placental perfusion and function may allow for treatment strategies in pregnancies complicated by IUGR or preeclampsia at early gestational ages when delivery is not an option (J Soc Gynecol Investig 2004; 11:16-21).

Another PPB-funded investigator has studied the complications associated with nuchal cord, in which the umbilical cord loops around the fetal neck. This common condition is observed in 16 percent to 35 percent of neonates at birth. The researcher found that antenatal nuchal cords usually occur randomly, with increased frequency in late gestation, and appear to be a normal part of intrauterine life that does not significantly increase the risk of acute- or labor-associated fetal hypoxia.

Investigators have also been exploring why neonates born to mothers who smoke have altered lung mechanics. In one study, rhesus monkeys exposed to nicotine in early and mid-gestation had increased thickness and increased collagen gene expression in their airway walls. The collagen production occurred in cells containing nicotine and acetylcholine, which suggests that nicotine can cross the placenta and directly affect lung development.

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