Insulin-like growth factor binding protein-1 at the maternal-fetal interface and insulin-like growth factor-I, insulin-like growth factor-II, and insulin-like growth factor binding protein-1 in the circulation of women with severe preeclampsia.
OBJECTIVE
Preeclampsia is characterized by maternal hypertension, proteinuria, edema, and shallow placental invasion. Insulin-like growth factor binding protein-1, abundant in maternal decidua, is believed to play a role in limiting trophoblast invasiveness. In this study we addressed the hypothesis that this binding protein is aberrantly expressed in preeclampsia. We also investigated circulating levels of insulin-like growth factor-I and insulin-like growth factor-II in subjects with severe preeclampsia compared with controls.


METHODS
Insulin-like growth factor binding protein-1 was investigated by immunohistochemistry at the maternal-fetal interface of eight pregnancies complicated by severe preeclampsia and six controls between 21 and 34 weeks of gestation. Cell types were identified with use of cell-specific markers. Circulating levels of insulin-like growth factor binding protein-1, insulin-like growth factor-I, and insulin-like growth factor-II in 16 patients with severe preeclampsia and 29 controls at the same gestational age were determined by an immunoradiometric assay and correlated with clinical parameters. Data were analyzed by t test and Pearson's method.


RESULTS
Insulin-like growth factor binding protein-1 was highly expressed on syncytiotrophoblasts, cytotrophoblasts, and decidual cells but not on placental fibroblasts. Immunostaining was greater at the maternal-fetal interface in severe preeclamptic patients compared with controls. Circulating insulin-like growth factor binding protein-1 levels in subjects with severe preeclampsia were 428.3 +/- 85.9 ng/ml compared with 76.6 +/- 11.8 in controls (p = 0.0007). Circulating insulin-like growth factor-I levels were 80.9 +/- 17.2 ng/ml compared with 179.4 +/- 28.2 ng/ml in controls (p = 0.0001). In contrast, insulin-like growth factor-II levels were not significantly different in the two groups. In subjects with severe preeclampsia insulin-like growth factor binding protein-1 levels correlated with diastolic blood pressure (r = 0.498, p 0.049) and aspartate transcarbamylase (0.621, p = 0.010).


CONCLUSIONS
The abundance of insulin-like growth factor binding protein-1 at the maternal-fetal interface in severely preeclamptic pregnancies suggests that the binding protein may participate in the pathogenesis of the shallow placental invasion observed in this disorder. Low circulating insulin-like growth factor-I and elevated insulin-like growth factor binding protein-1 levels may contribute to restricted placental and therefore fetal growth.
Giudice
L C
LC
Division of Reproductive Endocrinology, Stanford University Medical Center, CA 94305-5317, USA.
Martina
N A
NA
Crystal
R A
RA
Tazuke
S
S
Druzin
M
M
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D003656:Decidua / Q000737:chemistry*; D005260:Female; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000032:analysis* / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D007335:Insulin-Like Growth Factor II / Q000032:analysis*; D007752:Obstetric Labor, Premature / Q000097:blood / Q000473:pathology; D011225:Pre-Eclampsia / Q000097:blood / Q000473:pathology*; D011247:Pregnancy / Q000097:blood; D011262:Pregnancy Trimester, Second; D011263:Pregnancy Trimester, Third; D014327:Trophoblasts / Q000737:chemistry*
D018970:Insulin-Like Growth Factor Binding Protein 1; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II