Mid-Trimester Maternal ADAM12 Levels Differ According to Fetal Gender in Pregnancies Complicated by Preeclampsia

Abstract

An overrepresentation of adverse pregnancy outcomes has been observed in pregnancies associated with a male fetus. We investigated the association between fetal gender and candidate biomarkers for preeclampsia. Proteins were quantified in samples taken at 20 weeks from women recruited to the SCreening fOr Pregnancy Endpoints (SCOPE) study (preeclampsia n ¼ 150; no preeclampsia n ¼ 450). In contrast to placental growth factor, soluble endoglin, and insulin-like growth factor acid labile subunit, levels of metallopeptidase domain 12 (ADAM12) at 20 weeks were dependent on fetal gender in pregnancies complicated by preeclampsia, for male (n ¼ 73) fetuses the multiples of the median (MoM; interquartile range [IQR] 1.1-1.5) was 1.3, whereas for female fetuses (n ¼ 75) MoM was 1.1 (1.0-1.3); P < .01. Prediction of preeclampsia using ADAM12 levels was improved for pregnancies associated with a male fetus (area under receiver-operator curve [AUC] 0.73 [95% confidence interval [CI] 0.67-0.80]) than that of a female fetus .70]); P ¼ .03. The data presented here fit a contemporary hypothesis that there is a difference between the genders in response to an adverse maternal environment and suggest that an alteration in ADAM12 may reflect an altered placental response in pregnancies subsequently complicated by preeclampsia.

Fetal sexual dimorphism in systemic soluble fms‐like tyrosine kinase 1 among normotensive and preeclamptic women

“…Excessive inflammation is implicated in preeclampsia pathogenesis. 7,11,18 This is an avenue that should be examined further as antiangiogenic biomarkers are linked to placental phenotypes of preeclampsia. 3,5,15 Alternatively, studies have shown that fetuses respond differently to maternal inflammatory insults.…”

“…7,11,18 This is an avenue that should be examined further as antiangiogenic biomarkers are linked to placental phenotypes of preeclampsia. 7 Fetal sex could influence levels of antiangiogenic markers altering the risk of preeclampsia. 19,20 Both biomarkers may cause endothelial dysfunction, sFLT by impairing endothelial growth factor 21 and endoglin by impairing transforming growth factor signaling.…”

“…17 Other studies have reported sexual dimorphism in maternal angiogenic biomarkers. 7,11,18 This is an avenue that should be examined further as antiangiogenic biomarkers are linked to placental phenotypes of preeclampsia. 19 Two antiangiogenic markers in particular, endoglin and soluble fms-like tyrosine kinase 1 (sFLT), are consistently elevated in preeclampsia and may indicate more severe disease.…”

“…Only one other study of 125 preeclamptic women and 450 normotensive women has examined sexual dimorphism in serum endoglin 7. Only one other study of 125 preeclamptic women and 450 normotensive women has examined sexual dimorphism in serum endoglin 7.…”

“…3,5 Deriving sex-specific models to predict preeclampsia risk may be useful. 6,7 Unfortunately, the exact mechanisms by which fetal sex would influence pregnancy health remain unclear and understudied. ).…”