Uterine Artery Ligation in the Maternal Rat Alters Fetal Tissue Glucose Utilization

Abstract

LcI [2DG]t dt o [glucose] MAT ERIALS AND METHODSby which these conditions retard fetal growth and the processes th at are responsible for the neonatal hypoglycemia are not completely understood.Maternal uterine art ery ligati on has frequentl y been used to study the consequences of redu ced uterine blood flow on the fetu s. Th is procedur e severely retard s fetal growth in the rat (4-10). Previou s studies using this model have suggested that lim ited fetal nutrient availability and altered placental gaseous excha nge play important roles in the impairm ent of fetal growt h (5, 6). Restricted glucose delivery to th e developing fetus lead s to low levels of glucose, th e primary fetal metabolic substrate, and insulin, an important fetal growt h ho rm one (6). Uterine artery ligati on has been show n to pr odu ce fetal hypo xia, hypercapnia, and acidosis (6), which likely affect both cellular metabolism and fetal growth. This m odel is also associated with reduced glycogen sto res and delayed inductio n of gluco neogenic en zyme s (7,8). Th ese processes also app ear to be importa nt facto rs in th e development of hypoglycem ia in the small-for-gestationa l-age newborn ( I I, 12). Ho wever, sm all-for-gestati on al-age human infants may ha ve increa sed metabolic rat es (13, 14) and rapid clearance ofi.v. adm inistered glucose (15, 16), which could also contribute to the development of hypoglycemia.The effects of uterine artery ligation on fetal GU rem ain unknown. Knowledge of th ese effects may further define th e mechanisms responsible for altered fetal glucose homeostasis, IUGR, and neonatal hyp oglycemia. Studies of fetal GU, however, would be incomplete if individual tissue responses to ut erine artery ligation were not co nside red. Fetal brain growth is m inimally, if at all, affected by th is procedure, whereas hepatic growth is mark edly impaired (4, 5). Therefore, the effects on GU of individua l tissues may differ. Furthermore, these effects m ay change with tim e after the procedure. We therefore performed un ilateral uterine artery ligat ion s on pregnant rat s and measured GU of several major fetal tissues from fetu ses in the ligated and nonli gated ut erin e horn s at 24 and 48 h after ligation .We used a modification of SokolofT's 2DG method to measu re fetal rat tissue G U (17)(18)(19). 2DG is transported into th e cell and phosphorylated by hexokinase or glucokinase in a manner similar to glucose. Becau se of th e absence of the hydroxyl group at position 2, the phosph orylated product, 2DG6 P, is not furth er metab olized (17). Th e accum ulation of 2DG6P within a tissue can therefore be used to determ ine G U . The standard equa tion to measure GU of a parti cular tissue after an i.v. puls e of 2DG is:where [2DG6P] is the tissue con centration of 2DG6P at time T , 464 Abbreviations C U, glucose utilization IUCR, intrauterine growth retardation LC, lumped constant P k , placental discrimination constant 2DC, 2-deoxyglucose 2DC6P, 2-deoxyglucose-6-phosphate ABSTRACT. We studied the effects ...

Increased Rat Placental Fatty Acid, but Decreased Amino Acid and Glucose Transporters Potentially Modify Intrauterine Programming

“…By comparison of both groups with placentas from un‐operated control dams, we demonstrate an immediate, longitudinally stable reduction of GLUT‐1 in LIG placentas and a short reduction on day E20 in SOP placentas. Consistent with a down‐regulation of placental glucose transporters, it was demonstrated that fetal‐maternal glucose ratios are persistently reduced 24 and 48 h after uterine artery ligation [Lueder and Ogata, ]. Together with relatively increased fatty acid transport, this may result in a decreased respiratory quotient of the LIG and also SOP fetuses, with may have significant impact on programming energy metabolism.…”

Transient Rise of Glucose Uptake in the Fetal Rat Brain after Brief Episodes of Intrauterine Ischemia

“…While studying the long-term conse quences of ischemia on glucose transport and utilization in the fetal brain, Lueder and Ogata [14] showed that glucose utilization was reduced, 24 h after unilateral uterine artery ligation. At this time, cerebral glucose transport in the fetus did not differ from the control [15], In a different experimental model, cesarean-delivered preterm rats subjected to anoxia showed a substantial reduction in brain glucose levels in spite of adequate lev els of glucose in the circulation [8].…”

Epigenetics and fetal adaptation to perinatal events: Diversity through fidelity1

“…In our group, we have taken the approach of looking at representative “candidate” genes in multiple disparate models of perinatal insult. We have used animal models ranging from IUGR, produced by UPI (Lueder and Ogata, 1990; Lane et al, 1996) and maternal malnutrition (Desai et al, 2008), to mechanical ventilation (Albertine et al, 1999) to test the hypothesis that significant changes in the perinatal environment can 1) increase the risk of associated adult morbidities, such as diabetes; 2) affect perinatal and postnatal gene expression of the same candidate genes; and 3) modify the chromatin structure of relevant candidate genes.…”