Expression of insulin-like growth factor-I and placental growth hormone mRNA in placentae: a comparison between normal and intrauterine growth retardation pregnancies*
Shamim Sheikh
1
Purnima Satoskar
0
Deepa Bhartiya
1
0
Department of Obstetrics and Gynaecology, King Edward Memorial Hospital
, Acharya Donde Marg, Parel, Mumbai 400 012,
India
1
Cell Biology Department, Research Society, BJ Wadia Hospital for Children and Institute of Child Health
, Acharya Donde Marg, Parel, Mumbai 400 012
2
Some of the data were presented at the VII International conference of Reproductive Immunology
, New Delhi,
India
, October, 1998
Intrauterine growth restriction (IUGR) is generally defined as the pathological restriction of fetal growth resulting in a fetus with birth weight below the 10th percentile for gestational age. Almost 75% of IUGR cases develop during third trimester. Studies on animals (rodents and sheep) as well as humans suggest that insulin-like growth factor-I (IGF-I), under the influence of placental growth hormone (PGH) plays crucial roles in fetal growth regulation during this period. Limited data are available with regard to IGF-I and PGH in placentae of normal and IUGR births. Therefore, in the present study, IGF-I and PGH mRNA expression has been studied in term placentae of normal (n 10) and IUGR (n 15) births by in-situ hybridization procedure. Their expression was also studied in first (n 5) and second (n 5) trimester placentae obtained from elective termination of normal pregnancies. Both IGF-I and PGH expression were found to be higher in the first and second trimester placentae compared to term placentae in normal pregnancies. However, IUGR term placentae showed increased expression of both IGF-I and PGH mRNA in comparison with normal placentae. Various mechanisms leading to the increased transcription of IGF-I and PGH mRNA in IUGR placenta are discussed. This increased transcription perhaps occurs in response to the reduction in the fetal growth.
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The term intrauterine growth restriction (IUGR) is generally
assigned to the infants born with birth weights below the 10th
percentile for gestational age in that community/population,
as a result of a pathological restriction of fetal growth (Pollack
and Divon, 1992; Abu-Amero et al., 1998; Wollmann, 1998).
These babies are at high risk of developing metabolic and/or
cardiovascular diseases and other complications in post-natal
life (Barker, 1995). Major factors leading to IUGR include
placental/ fetal factors like chromosomal abnormalities, fetal
congenital malformations, placental pathology, intrauterine
infections and maternal factors such as pre-eclampsia, maternal
cardiovascular disease, or other maternal complications.
However, the aetiology of the majority of IUGR cases remains
unexplained (Vander Veen and Fox, 1983; Gluckman and
Harding, 1997; Abu-Amero et al., 1998; Wollmann, 1998).
Insulin-like growth factors I and II (IGF-I and IGF-II)
have been implicated to play important roles in fetal growth
regulation (Giudice et al., 1995; Klauwer et al., 1997), although
their relative importance still remains controversial. Gene
knock-out experiments done on mice and other studies
conducted on animals (rodents and sheep) as well as humans
suggest that in the third trimester, the key feature of fetal
growth is the supply of nutrients from the mother to the fetus
through placenta. During this period, IGF-I (in maternal,
placental and fetal compartments) becomes the dominant
regulator of fetal growth, since it not only influences
partitioning of nutrients between placenta and fetus but also
promotes fetal somatogenesis and fetal nutrient uptake (Baker
et al., 1993; Gluckman, 1995; Gluckman and Harding, 1997).
Several investigators have studied the concentrations of IGF
in cord blood and maternal circulation in IUGR versus normal
pregnancies. IGF-I concentrations were found to be
significantly lower in cord blood of IUGR infants compared to
normal (Guidice et al., 1995; Klauwer et al., 1997; S.Sheik
et al., unpublished observations). IGF-I concentrations in
maternal circulation were also found to be significantly lower
in pregnancies complicated by IUGR (Mirless et al., 1993;
Holms et al., 1998; unpublished observations). Placental IGF,
in both normal and IUGR pregnancies, has recently been
studied for the first time (Abu-Amero et al., 1998). They
reported an increased expression of IGF-II mRNA in IUGR
term placentae compared to normal placentae, but found no
significant difference in IGF-I mRNA expression between the
two groups.
The majority of IUGR cases (almost 75%) generally develop
during the second half of the pregnancy (Wollman et al.,
1998), when IGF-I may be playing a major role in fetal growth
regulation. Alterations in its concentrations and/or its activity
in maternal, fetal and placental compartments may be one of
the mechanisms involved in the pathogenesis of idiopathic
IUGR cases.
In the present study, IGF-I mRNA expression was
investigated in situ in normal versus IUGR placentae. Both maternal
and placental IGF-I concentrations appear to be regulated by
placental growth hormone (PGH), which (...truncated)