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Article

Increased HLA-G Expression in Term Placenta of Women with a History of Recurrent Miscarriage Despite Their Genetic Predisposition to Decreased HLA-G Levels

1
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
2
Department of Laboratory Medicine, Laboratory of Medical Immunology, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, The Netherlands
3
Department of Obstetrics and Gynaecology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(3), 625; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20030625
Received: 20 December 2018 / Revised: 28 January 2019 / Accepted: 29 January 2019 / Published: 1 February 2019
(This article belongs to the Special Issue Reproductive Immunology: Cellular and Molecular Biology)
Human leukocyte antigen (HLA)-G is an immune modulating molecule that is present on fetal extravillous trophoblasts at the fetal-maternal interface. Single nucleotide polymorphisms (SNPs) in the 3 prime untranslated region (3′UTR) of the HLA-G gene can affect the level of HLA-G expression, which may be altered in women with recurrent miscarriages (RM). This case-control study included 23 women with a medical history of three or more consecutive miscarriages who delivered a child after uncomplicated pregnancy, and 46 controls with uncomplicated pregnancy. Genomic DNA was isolated to sequence the 3′UTR of HLA-G. Tissue from term placentas was processed to quantify the HLA-G protein and mRNA levels. The women with a history of RM had a lower frequency of the HLA-G 3′UTR 14-bp del/del genotype as compared to controls (Odds ratio (OR) 0.28; p = 0.039), which has previously been related to higher soluble HLA-G levels. Yet, HLA-G protein (OR 6.67; p = 0.006) and mRNA (OR 6.33; p = 0.010) expression was increased in term placentas of women with a history of RM as compared to controls. In conclusion, during a successful pregnancy, HLA-G expression is elevated in term placentas from women with a history of RM as compared to controls, despite a genetic predisposition that is associated with decreased HLA-G levels. These findings suggest that HLA-G upregulation could be a compensatory mechanism in the occurrence of RM to achieve an ongoing pregnancy. View Full-Text
Keywords: HLA-G; immunohistochemistry; placenta; pregnancy; recurrent miscarriage HLA-G; immunohistochemistry; placenta; pregnancy; recurrent miscarriage
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MDPI and ACS Style

Craenmehr, M.H.C.; Nederlof, I.; Cao, M.; Drabbels, J.J.M.; Spruyt-Gerritse, M.J.; Anholts, J.D.H.; Kapsenberg, H.M.; Stegehuis, J.A.; van der Keur, C.; Fasse, E.; Haasnoot, G.W.; van der Hoorn, M.-L.P.; Claas, F.H.J.; Heidt, S.; Eikmans, M. Increased HLA-G Expression in Term Placenta of Women with a History of Recurrent Miscarriage Despite Their Genetic Predisposition to Decreased HLA-G Levels. Int. J. Mol. Sci. 2019, 20, 625. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20030625

AMA Style

Craenmehr MHC, Nederlof I, Cao M, Drabbels JJM, Spruyt-Gerritse MJ, Anholts JDH, Kapsenberg HM, Stegehuis JA, van der Keur C, Fasse E, Haasnoot GW, van der Hoorn M-LP, Claas FHJ, Heidt S, Eikmans M. Increased HLA-G Expression in Term Placenta of Women with a History of Recurrent Miscarriage Despite Their Genetic Predisposition to Decreased HLA-G Levels. International Journal of Molecular Sciences. 2019; 20(3):625. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20030625

Chicago/Turabian Style

Craenmehr, Moniek H.C., Iris Nederlof, Milo Cao, Jos J.M. Drabbels, Marijke J. Spruyt-Gerritse, Jacqueline D.H. Anholts, Hanneke M. Kapsenberg, Janine A. Stegehuis, Carin van der Keur, Esther Fasse, Geert W. Haasnoot, Marie-Louise P. van der Hoorn, Frans H.J. Claas, Sebastiaan Heidt, and Michael Eikmans. 2019. "Increased HLA-G Expression in Term Placenta of Women with a History of Recurrent Miscarriage Despite Their Genetic Predisposition to Decreased HLA-G Levels" International Journal of Molecular Sciences 20, no. 3: 625. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20030625

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