ABSTRACT
Objective
Women pregnant after oocyte donation (OD) are prone to develop preeclampsia, a syndrome characterised by an aberrant immunologic response, hypercoagulability and endothelial dysfunction. A mediator of inflammation and coagulation is thrombomodulin; a possible role player in this syndrome. Our objective is to investigate whether thrombomodulin dysregulation is involved in the development of preeclampsia after OD.
Design
Case-control study.
Setting
Women who received OD in the LUMC or in the nearby teaching hospitals between 2004 and 2013.
Patient(s)
A total of 109 placentas of uncomplicated pregnancies (48 naturally conceived, 21 IVF and 40 OD pregnancies) and 16 placentas of OD pregnancies complicated by preeclampsia.
Intervention(s)
None
Measurements
Abundance of thrombomodulin protein and vitamin D receptor (VDR) were determined using...
Show moreABSTRACT
Objective
Women pregnant after oocyte donation (OD) are prone to develop preeclampsia, a syndrome characterised by an aberrant immunologic response, hypercoagulability and endothelial dysfunction. A mediator of inflammation and coagulation is thrombomodulin; a possible role player in this syndrome. Our objective is to investigate whether thrombomodulin dysregulation is involved in the development of preeclampsia after OD.
Design
Case-control study.
Setting
Women who received OD in the LUMC or in the nearby teaching hospitals between 2004 and 2013.
Patient(s)
A total of 109 placentas of uncomplicated pregnancies (48 naturally conceived, 21 IVF and 40 OD pregnancies) and 16 placentas of OD pregnancies complicated by preeclampsia.
Intervention(s)
None
Measurements
Abundance of thrombomodulin protein and vitamin D receptor (VDR) were determined using immunohistochemistry. mRNA expression was determined using qPCR.
Result(s)
Placental thrombomodulin protein abundance was lower in OD pregnancies(diffuse pattern in 45%) than in controls(diffuse pattern in 96%;p<0.001). Placental thrombomodulin mRNA expression was lower in OD pregnancies complicated by preeclampsia(0.72±0.47) compared with uncomplicated OD pregnancies(0.43±0.18;p<0.001). Thrombomodulin expression correlated with inflammation and coagulation. VDR expression was decreased in OD pregnancies complicated by preeclampsia and correlated with thrombomodulin mRNA.
Conclusion(s)
Pregnancies conceived through OD lose placental thrombomodulin expression. This loss is associated with an increased coagulation and inflammation, and indicates that endothelial protection is diminished in OD pregnancies, which might be an explanation for the increased risk for preeclampsia. The vitamin D metabolism is dysregulated in OD pregnancies and might be a target for therapy.
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