The effect of alterations in placental blood flow on the growth of and nutrient supply to the fetal guinea‐pig.

Abstract

SUMMARY1. The distribution of the cardiac output and the maternal placental blood flow has been measured in guinea-pigs at days 49-51 of pregnancy using radioactively labelled microspheres. In some instances uterine blood flow was reduced chronically by ligating one uterine artery at day 30 of pregnancy.2. Between 3 and 4 % of the cardiac output passed normally to placenta, and this could be reduced to < 2 % after uterine artery ligation. The result of the ligation was to reduce fetal and placental weight by up to 70 %.3. Fetal and placental weight showed a close linear correlation in controls and in pregnancies with uterine artery ligation. However, when placental size was reduced below 60 % of control, fetal weight was less affected by a reduction in placental weights than normal.4. Placental blood flow and placental size exhibited a close linear relationship over the whole range of values, but there was limiting placental weight which approached 1-3 g as placental blood flow approached zero. Thus a reduced placental size, particularly below about 50 %, was associated with a proportionately greater reduction in maternal placental blood flow.5. Maternal placental blood flow or the percentage of maternal cardiac output to the placenta and fetal weight also showed a well-correlated linear relationship.However, when placental blood flow was below about 50 % of control values further reduction had a less than normal effect upon fetal growth.6. Small fetuses were hypoglycaemic and hypoinsulinaemic and the degree of each was dependent upon the extent of the reduction in fetal weight and in maternal placental blood flow. In fetuses that were below about 40 % of normal size, and in which placental blood was below about 30 % of control, fetal weight was less sensitive to falls in blood glucose, which in turn was more sensitive than normal to a fall in maternal placental blood flow.7. The results indicate that over the range of 50-100% of normal fetal growth, maternal placental blood flow and probably nutrient supply to the fetus vary in parallel. Hence over this range fetal and placental growth rates are determined in

Central stiffening in adulthood linked to aberrant aortic remodeling under suboptimal intrauterine conditions

“…Chronic placental insufficiency was induced in time-mated guinea pigs by UAL. This technique is commonly used to impair intrauterine growth in rodents (2,9), since it depletes uterine capacity leading to discordant fetal growth within litters and variable fetal growth restriction (14,19,20). Pregnant guinea pigs at 28 -30 days of gestation (term ϳ67 days) were induced in an anesthetic chamber (4 -5% isoflurane with 2 l/min O 2; followed by 2.5-3% isoflurane with 1 l/min O 2 for maintenance).…”

“…Growth of the fetal guinea pig was impaired by means of an established model of placental insufficiency, whereby placental blood flow is reduced throughout the second half of gestation by uterine artery ligation (UAL) (19,20). The effects of growth restriction on aortic development in the near-term fetus were assessed by measurement of wall dimensions, ECM protein composition, VSMC content, and phenotype.…”

Programming the brain: Common outcomes and gaps in knowledge from animal studies of IUGR

“…Effects on fetal nutrient supply and metabolism also differ 164 between the various models of IUGR (Table 1). For example, fetal blood glucose does not appear to 165 be reduced by maternal protein restriction in rats [104,105], but is reduced in other models of 166 IUGR, such as utero-placental ligation in the guinea pig and in both utero-placental embolisation 167 and carunclectomy-induced placental restriction in sheep [11,[106][107][108][109][110][111]. 168 169 One particular limitation of models of maternal nutrient restriction in rodents is that the restriction 170 is imposed only during earlier stages of neurodevelopment than are affected by IUGR in humans.…”

Dysregulation of methylation and expression of imprinted genes in oocytes and reproductive tissues in mice of advanced maternal age

“…Decreased nutrient supply has been associated with fetal growth restriction and smaller placental weights in guinea-pigs [48,49], sheep [50], rats [51], and cattle [52]. Growth restricted placentas in the mouse are capable of maintaining normal fetal growth until late in gestation, in part by increasing the expression of glucose (Slc2a3/GLUT3) and System A amino acid (Slc38a4/SNAT4) transporters [53].…”