Recurrent pregnancy loss (RPL) is a poorly understood condition that comes with many uncertainties, both for affected couples and healthcare providers. Important goals are to provide answers to... Show moreRecurrent pregnancy loss (RPL) is a poorly understood condition that comes with many uncertainties, both for affected couples and healthcare providers. Important goals are to provide answers to these couples and to improve their pregnancy outcomes. To achieve this, we need a better understanding of contributing and predictive factors. Until now, the male role in RPL has been underexposed. In this thesis, we aimed to expand our knowledge regarding the ‘forgotten father’ in RPL. We have found strong clues that in RPL, male contribution really matters.The main conclusions are that advanced paternal age and paternal smoking are associated with an increased risk of pregnancy loss, that inclusion of paternal factors into a prediction model improves the accuracy of predicting ongoing pregnancy after RPL, and that impaired immunomodulatory effects of seminal plasma may play a role in RPL. At the same time, our studies have led to new questions and uncovered new challenges, which are excellent opportunities for further research. Show less
Fosse, N.A. du; Lashley, E.E.L.O.; Anholts, J.D.H.; Beelen, E. van; Cessie, S. le; Lith, J.M.M. van; ... ; Hoorn, M.L.P. van der 2022
Background: Seminal plasma contains signaling molecules capable of modulating the maternal immune environment to support implantation and pregnancy. Prior studies indicated that seminal plasma... Show moreBackground: Seminal plasma contains signaling molecules capable of modulating the maternal immune environment to support implantation and pregnancy. Prior studies indicated that seminal plasma induces changes in gene transcription of maternal immune cells. Reduced immune suppressive capacity may lead to pregnancy loss. The aim of this study was to investigate the immunomodulating effects of seminal plasma on T cells and monocytes in the context of recurrent pregnancy loss (RPL).Methods: Female T cells and monocytes were incubated with seminal plasma of 20 males in unexplained RPL couples (RPL males) and of 11 males whose partners had ongoing pregnancies (control males). The effect of seminal plasma on messenger RNA (mRNA) expression of immune cells was measured. Levels of mRNA expression were related to key signaling molecules present in the seminal plasma. Agglomerative hierarchical cluster analysis was performed on seminal plasma expression profiles and on mRNA expression profiles. Results: Expression of CD25 and anti-inflammatory IL-10 by female T cells was significantly lower after stimulation with seminal plasma of RPL males compared to control males. Female monocytes treated with seminal plasma of RPL males showed an immune activation signature of relatively elevated HLA-DR expression. Expression of these T cell and monocyte components was particularly correlated with the amounts of TGF-beta and VEGF in the seminal plasma. Conclusion: Our findings indicate that seminal plasma has immunomodulating properties on female immune cells compatible with the induction of a more regulatory phenotype, which may be impaired in cases of unexplained RPL. Show less
Every pregnancy is unique due to distinct maternal, paternal and fetal factors. Presumably, the immunological response differs between pregnancies, and certain pregnancies could be immunologically... Show moreEvery pregnancy is unique due to distinct maternal, paternal and fetal factors. Presumably, the immunological response differs between pregnancies, and certain pregnancies could be immunologically more challenging for the mother than others. In the present thesis, pregnancies presumed to be more immunologically challenging were studied. For example, in oocyte donation pregnancies, the fetus is completely allogeneic for the mother. Furthermore, based on findings in pregnancies complicated by pre-eclampsia and chronic intervillositis of unknown etiology (CIUE), it is postulated that the immune system plays a significant role in such pathophysiology. This thesis investigated oocyte donation pregnancies with and without pre-eclampsia and naturally conceived pregnancies complicated by pre-eclampsia or CIUE. Investigating immunologically challenging pregnancies improves our understanding of naturally conceived pregnancies and provides an interesting setting in which to test hypotheses relevant to transplantation immunology and tumour immunology. Henceforth, new discoveries in reproductive immunology could result in novel insights into the dynamics of the immune system. Future research should focus on more continuous study of the fetal-maternal interface during pregnancy and exploit the unique circumstances provided by some of the specific complications of pregnancy, such as FNAIT, ectopic pregnancies and placenta accreta. Show less
Hoorn, M.L.P. van der; Egmond, A. van; Swings, G.M.J.S.; Beelen, E. van; Keur, C. van der; Tirado-Gonzalez, I.; ... ; Scherjon, S.A. 2014
The aim of this thesis was to gain a better understanding of the immunoregulatory mechanisms associated with maternal tolerance of the fetus during pregnancy. The distribution of decidual... Show moreThe aim of this thesis was to gain a better understanding of the immunoregulatory mechanisms associated with maternal tolerance of the fetus during pregnancy. The distribution of decidual leukocytes, specifically uterine NK cells and T cells, in the decidua basalis and parietalis were studied in the setting of normal term pregnancy, following elective cesarean section or spontaneous vaginal delivery, in the setting of complicated pregnancy, and in the setting of assisted reproduction, and to study the function of term decidual leukocytes, specifically proliferation and cytokine production, in response to fetal and allogeneic blood leukocytes. Techniques involving flow cytometry, immunohistochemistry and mixed lymphocyte cultures were used to perform these studies. Show less
