title: Loss of placental thrombomodulin in oocyte donation pregnancies.
abstract: To investigate whether thrombomodulin dysregulation is involved in the development of preeclampsia after oocyte donation (OD). Women who become pregnant after OD are prone to develop preeclampsia, a syndrome characterized by an aberrant immunologic response, hypercoagulability, and endothelial dysfunction. A mediator of inflammation and coagulation is thrombomodulin, which has a possible role to play in this syndrome.
  
  
  
  Case-control study.
  
  
  
  Not applicable.
  
  
  
  Placentas from 82 women with an uncomplicated pregnancy (48 naturally conceived, 21 IVF, and 33 OD pregnancies) and 9 women with an OD pregnancy complicated by preeclampsia have been studied.
  
  
  
  None.
  
  
  
  Abundances of thrombomodulin protein and vitamin D receptor (VDR) were determined using immunohistochemistry; mRNA expression was determined using quantitative polymerase chain reaction.
  
  
  
  Placental thrombomodulin protein abundance was lower in OD pregnancies (diffuse pattern in 45%) than in controls (diffuse pattern in 96%). Placental thrombomodulin mRNA expression was lower in OD pregnancies complicated by preeclampsia (0.72 ± 0.47) compared with in uncomplicated OD pregnancies (0.43 ± 0.18). Thrombomodulin expression correlated with inflammation and coagulation. VDR expression was decreased in OD pregnancies complicated by preeclampsia and was correlated with thrombomodulin mRNA.
  
  
  
  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. Vitamin D metabolism is dysregulated in OD pregnancies and might be a target for therapy.
authors: Department of Pathology, Leiden University Medical Centre, Leiden, the Netherlands. Electronic address: m.bos@lumc.nl.
authors: Manon
authors: M
authors: Bos
authors: Department of Pathology, Leiden University Medical Centre, Leiden, the Netherlands.
authors: Hans J
authors: HJ
authors: Baelde
authors: Department of Pathology, Leiden University Medical Centre, Leiden, the Netherlands.
authors: Jan A
authors: JA
authors: Bruijn
authors: Department of Obstetrics, University Medical Center Utrecht, Wilhelmina Children's Hospital, Utrecht, the Netherlands.
authors: Kitty W M
authors: KW
authors: Bloemenkamp
authors: Department of Obstetrics, Leiden University Medical Centre, Leiden, the Netherlands.
authors: Marie-Louise P
authors: MP
authors: van der Hoorn
authors: Department of Pathology, Leiden University Medical Centre, Leiden, the Netherlands.
authors: Rosanne J
authors: RJ
authors: Turner
mesh_terms: D000328:Adult; D001777:Blood Coagulation; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D015536:Down-Regulation; D010064:Embryo Implantation; D004624:Embryo Transfer; D005260:Female; D005298:Fertility; D005307:Fertilization in Vitro / Q000009:adverse effects*; D006801:Humans; D007246:Infertility / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*; D018836:Inflammation Mediators / Q000378:metabolism; D008875:Middle Aged; D018587:Oocyte Donation / Q000009:adverse effects*; D010920:Placenta / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000097:blood / Q000209:etiology* / Q000235:genetics; D011247:Pregnancy; D018873:Pregnancy Rate; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors; D018180:Thrombomodulin / Q000235:genetics / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D018836:Inflammation Mediators; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; C546931:THBD protein, human; D018180:Thrombomodulin; C579457:VDR protein, human
keywords: Preeclampsia; oocyte donation; placenta; thrombomodulin; vitamin D