It has been recognized that Intrauterine Growth Restriction
(IUGR) is commonly due to placental dysfunction associated with both genetic and environmental factors. Nonetheless, the
molecular mechanism of IUGR remains largely unexplored.
IUGR is more common with maternal age around 20 years, and above 35 years. IUGR is also predicted by a subnormal gestational weight gain in the mother.
Placental IGF-II and IGFBP-3 gene activities are both higher in IUGR fetuses compared to normal fetuses. This suggests a possible relationship between IUGR in the fetus and chronic
diseases in the subsequent adult. Placental IGF-II gene activity is also higher in male compared to female IUGR fetuses. This may be explained by differences in gender-related development of non-specific body characteristics. Umbilical cord glucose and insulin concentrations are both
significantly lower in IUGR when compared to normal fetuses.
In placental samples obtained from IUGR pregnancies, the
antiapoptotic Bcl-2 gene is underexpressed compared to normal pregnancies. In contrast, activity by the proapoptotic Bax
gene is not significantly different in IUGR compared to normal
pregnancies. Thus, the enhanced apoptotic activity found in IUGR can be explained by a decreased Bcl-2 gene activity
and not through increased stimulation by the Bax gene.
There is also a decreased activity of the 11-β-hydroxysteroid
dehydrogenase 2 gene in IUGR compared to normal pregnancy. The decreased activity of this gene results in a dysfunctional
placental barrier, leading to impaired placental defense against maternal glucocorticoids. Maternal glucocorticoids play an important role in the development of fetal programming in a fashion similar to analogous effects by IGF-II and IGFBP-3. Unopposed maternal glucocorticoid exposure can predict an increased propensity for several forms of chronic
diseases in adult life. This decrease in gene activity of the
11-β-hydroxysteroid dehydrogenase 2 gene becomes detectable only after gestational week 33. The activity of this gene is also decreased in cases of fetal asphyxia associated with IUGR
