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Article ; Online: Impaired immunomodulatory effects of seminal plasma may play a role in unexplained recurrent pregnancy loss: Results of an in vitro study.

du Fossé, N A / Lashley, E E L O / Anholts, J D H / van Beelen, E / le Cessie, S / van Lith, J M M / Eikmans, M / van der Hoorn, M L P

Journal of reproductive immunology

2022 Volume 151, Page(s) 103500

Abstract: Background: 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 ... ...

Abstract	Background: 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-β 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.
MeSH term(s)	Abortion, Habitual ; Female ; Humans ; Immunomodulation ; Male ; Pregnancy ; RNA, Messenger/metabolism ; Semen ; T-Lymphocytes/metabolism
Chemical Substances	RNA, Messenger
Language	English
Publishing date	2022-02-19
Publishing country	Ireland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	424421-7
ISSN	1872-7603 ; 0165-0378
ISSN (online)	1872-7603
ISSN	0165-0378
DOI	10.1016/j.jri.2022.103500
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Article ; Online: Exploring gender differences among couples with unexplained recurrent pregnancy loss regarding preferences for supportive care.

du Fossé, N A / Lashley, E E L O / Treurniet, T T / van Lith, J M M / le Cessie, S / Boosman, H / van der Hoorn, M L P

BMC pregnancy and childbirth

2021 Volume 21, Issue 1, Page(s) 796

Abstract: Background: International guidelines recommend to offer supportive care during a next pregnancy to couples affected by recurrent pregnancy loss (RPL). In previous research, several options for supportive care have been identified and women's preferences ...

Abstract	Background: International guidelines recommend to offer supportive care during a next pregnancy to couples affected by recurrent pregnancy loss (RPL). In previous research, several options for supportive care have been identified and women's preferences have been quantified. Although it is known that RPL impacts the mental health of both partners, male preferences for supportive care have hardly been explored. Methods: A cross-sectional study was conducted in couples who visited a specialized RPL clinic in the Netherlands between November 2018 and December 2019. Both members of the couples received a questionnaire that quantified their preferences for supportive care in a next pregnancy and they were asked to complete this independently from each other. Preferences for each supportive care option were analysed on a group level (by gender) and on a couple level, by comparing preferences of both partners. Results: Ninety-two questionnaires (completed by 46 couples) were analysed. The overall need for supportive care indicated on a scale from 1 to 10 was 6.8 for men and 7.9 for women (P = 0.002). Both genders preferred to regularly see the same doctor with knowledge of their obstetric history, to make a plan for the first trimester and to have frequent ultrasound examinations. A lower proportion of men preferred a doctor that shows understanding (80% of men vs. 100% of women, P = 0.004) and a doctor that informs on wellbeing (72% vs. 100%, P = ≤0.000). Fewer men preferred support from friends (48% vs. 74%, P = 0.017). Thirty-seven percent of men requested more involvement of the male partner at the outpatient clinic, compared to 70% of women (P = 0.007). In 28% of couples, partners had opposing preferences regarding peer support. Conclusions: While both women and men affected by RPL are in need of supportive care, their preferences may differ. Current supportive care services may not entirely address the needs of men. Health care professionals should focus on both partners and development of novel supportive care programs with specific attention for men should be considered.
MeSH term(s)	Abortion, Habitual/psychology ; Adult ; Cross-Sectional Studies ; Fathers/psychology ; Female ; Humans ; Male ; Netherlands ; Patient Preference/psychology ; Prenatal Care ; Psychosocial Support Systems ; Surveys and Questionnaires
Language	English
Publishing date	2021-11-30
Publishing country	England
Document type	Journal Article
ISSN	1471-2393
ISSN (online)	1471-2393
DOI	10.1186/s12884-021-04277-4
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Article ; Online: Identification of distinct seminal plasma cytokine profiles associated with male age and lifestyle characteristics in unexplained recurrent pregnancy loss.

du Fossé, N A / Lashley, E E L O / van Beelen, E / Meuleman, T / le Cessie, S / van Lith, J M M / Eikmans, M / van der Hoorn, M L P

Journal of reproductive immunology

2021 Volume 147, Page(s) 103349

Abstract: Background: Seminal plasma contains a wide range of cytokines, chemokines and growth factors. Part of these signalling molecules assist in inducing a state of active maternal immune tolerance towards the fetus. Disbalances in seminal plasma content may ... ...

Abstract	Background: Seminal plasma contains a wide range of cytokines, chemokines and growth factors. Part of these signalling molecules assist in inducing a state of active maternal immune tolerance towards the fetus. Disbalances in seminal plasma content may contribute to pregnancy loss. This study investigated cytokine expression profiles in seminal plasma of male partners of couples with unexplained recurrent pregnancy loss (RPL) and the association with clinical and lifestyle characteristics, including smoking, alcohol consumption and body mass index (BMI). Methods: In the seminal plasma of 52 men who visited a specialised RPL clinic the levels of 25 pre-selected cytokines, chemokines and growth factors were measured by Bio-Plex assay or ELISA. Two-way hierarchical cluster analysis was performed. Identified patient clusters were compared on clinical and lifestyle characteristics. Results: Two distinct cytokine expression profiles in the seminal plasma were revealed by cluster analysis. Patient cluster I showed relatively higher levels of pro-inflammatory cytokines, including IL-1α, IL-1β, IL-6, IL-8, IL-12, IL-18 and TNF-α, compared to Patient cluster II. Men belonging to Patient cluster I were significantly older and had significantly more lifestyle risk factors compared to men in Patient cluster II. Conclusion: Cluster analysis suggested the existence of a less favourable pro-inflammatory cytokine expression profile, being present in part of men affected by RPL and associated with advanced male age and lifestyle risk factors. These findings may serve as a starting point for further research into underlying mechanisms and ultimately lead to novel diagnostic and therapeutic approaches for couples with RPL.
MeSH term(s)	Abortion, Habitual/diagnosis ; Abortion, Habitual/immunology ; Adult ; Age Factors ; Biomarkers/analysis ; Biomarkers/metabolism ; Case-Control Studies ; Cytokines/analysis ; Cytokines/metabolism ; Female ; Healthy Volunteers ; Humans ; Male ; Pregnancy ; Prognosis ; Semen/immunology ; Semen/metabolism ; Semen Analysis/methods
Chemical Substances	Biomarkers ; Cytokines
Language	English
Publishing date	2021-07-08
Publishing country	Ireland
Document type	Journal Article ; Observational Study
ZDB-ID	424421-7
ISSN	1872-7603 ; 0165-0378
ISSN (online)	1872-7603
ISSN	0165-0378
DOI	10.1016/j.jri.2021.103349
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Article ; Online: Detailed immune monitoring of a pregnant woman with critical Covid-19.

du Fossé, N A / Bronsgeest, K / Arbous, M S / Zlei, M / Myeni, S K / Kikkert, M / van Dongen, Jjm / Staal, Fjt / van der Hoorn, Mlp / van den Akker, T

Journal of reproductive immunology

2020 Volume 143, Page(s) 103243

Abstract: A primigravid woman with Covid-19 related respiratory insufficiency was admitted into a tertiary Intensive Care Unit at 23 3/7 weeks' gestation. Highly sensitive flow cytometry of peripheral leukocytes indicated significantly suppressed naïve T- and B- ... ...

Abstract	A primigravid woman with Covid-19 related respiratory insufficiency was admitted into a tertiary Intensive Care Unit at 23 3/7 weeks' gestation. Highly sensitive flow cytometry of peripheral leukocytes indicated significantly suppressed naïve T- and B-cell compartments. The suppressed immune cell responses led us keep the initially started administration of corticosteroids for fetal and maternal indication at a low dose. After three weeks her B-cell response peaked, SARS-CoV-2 was cleared and clinical improvement ensued a week later. At 28 weeks' gestation, a son of 1570 g was born by cesarean section. She was extubated two days postpartum and discharged from hospital 5.5 weeks postpartum.
MeSH term(s)	Adult ; B-Lymphocytes/immunology ; COVID-19/diagnosis ; COVID-19/immunology ; Cesarean Section ; Critical Care ; Female ; Flow Cytometry ; Gravidity ; Humans ; Immunosuppression ; Pregnancy/immunology ; Pregnancy Complications, Infectious/diagnosis ; Respiratory Insufficiency/diagnosis ; SARS-CoV-2/physiology ; T-Lymphocytes/immunology
Keywords	covid19
Language	English
Publishing date	2020-10-29
Publishing country	Ireland
Document type	Case Reports ; Journal Article
ZDB-ID	424421-7
ISSN	1872-7603 ; 0165-0378
ISSN (online)	1872-7603
ISSN	0165-0378
DOI	10.1016/j.jri.2020.103243
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Article ; Online: Evaluating the role of paternal factors in aetiology and prognosis of recurrent pregnancy loss: study protocol for a hospital-based multicentre case-control study and cohort study (REMI III project).

du Fossé, Nadia / van der Hoorn, Marie-Louise / Eikmans, Michael / Heidt, Sebastiaan / le Cessie, Saskia / Mulders, Annemarie / van Lith, Jan / Lashley, Eileen

BMJ open

2019 Volume 9, Issue 11, Page(s) e033095

Abstract: Introduction: Recurrent pregnancy loss (RPL) is defined as the spontaneous demise of two or more pregnancies before the fetus reaches viability. Despite investigation of multiple known maternal risk factors, in more than 50% of couples, this condition ... ...

Abstract	Introduction: Recurrent pregnancy loss (RPL) is defined as the spontaneous demise of two or more pregnancies before the fetus reaches viability. Despite investigation of multiple known maternal risk factors, in more than 50% of couples, this condition remains unexplained. Studies focusing on paternal factors in RPL are scarce, and therefore, paternal evaluation in RPL is currently very limited. However, regarding single miscarriage, there are multiple publications suggesting a contributive role of paternal factors. In this project, we aim to identify paternal factors associated with RPL and to improve couple-specific prediction of future pregnancy outcomes by developing a prediction model containing both maternal and paternal factors. Methods and analysis: In a case-control design, the relation between unexplained RPL and paternal age, lifestyle factors, sperm DNA damage and immunomodulatory factors in peripheral blood and semen will be studied. Prospectively, 135 couples with naturally conceived unexplained RPL (cases) and 135 fertile couples without a history of pregnancy loss (controls) will be included, with collection of paternal blood and semen samples and documentation of clinical and lifestyle characteristics. In addition, 600 couples from both groups will be included retrospectively. To adjust for confounders, multivariate logistic regression will be used. The predictive value of paternal and maternal factors will be studied in the total RPL cohort consisting of approximately 735 couples. The primary outcome of the cohort study is live birth within 5 years after initial visit of the clinic. Secondary outcomes are ongoing pregnancy, time interval until next pregnancy and pregnancy complications. Ethics and dissemination: This project is approved by the Medical Research Ethics Committee of the Leiden University Medical Center. No risks or burden are expected from the study. The findings of this study will be disseminated via peer-reviewed publications and presentations at international conferences. Trial registration number: NL7762.
MeSH term(s)	Abortion, Habitual/diagnosis ; Abortion, Habitual/etiology ; Adult ; Case-Control Studies ; Cohort Studies ; Female ; Humans ; Logistic Models ; Male ; Multivariate Analysis ; Pregnancy ; Pregnancy Outcome ; Prognosis ; Research Design ; Tissue Array Analysis
Language	English
Publishing date	2019-11-14
Publishing country	England
Document type	Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2019-033095
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Engineering the Band Alignment in QD Heterojunction Films via Ligand Exchange.

Grimaldi, Gianluca / van den Brom, Mark J / du Fossé, Indy / Crisp, Ryan W / Kirkwood, Nicholas / Gudjonsdottir, Solrun / Geuchies, Jaco J / Kinge, Sachin / Siebbeles, Laurens D A / Houtepen, Arjan J

The journal of physical chemistry. C, Nanomaterials and interfaces

2019 Volume 123, Issue 49, Page(s) 29599–29608

Abstract: Colloidal quantum dots (QDs) allow great flexibility in the design of optoelectronic devices, thanks to their size-dependent optical and electronic properties and the possibility to fabricate thin films with solution-based processing. In particular, in ... ...

Abstract	Colloidal quantum dots (QDs) allow great flexibility in the design of optoelectronic devices, thanks to their size-dependent optical and electronic properties and the possibility to fabricate thin films with solution-based processing. In particular, in QD-based heterojunctions, the band gap of both components can be controlled by varying the size of the QDs. However, control over the band alignment between the two materials is required to tune the dynamics of carrier transfer across a heterostructure. We demonstrate that ligand exchange strategies can be used to control the band alignment of PbSe and CdSe QDs in a mixed QD solid, shifting it from a type-I to a type-II alignment. The change in alignment is observed in both spectroelectrochemical and transient absorption measurements, leading to a change in the energy of the conduction band edges in the two materials and in the direction of electron transfer upon photoexcitation. Our work demonstrates the possibility to tune the band offset of QD heterostructures via control of the chemical species passivating the QD surface, allowing full control over the energetics of the heterostructure without requiring changes in the QD composition.
Language	English
Publishing date	2019-11-19
Publishing country	United States
Document type	Journal Article
ISSN	1932-7447
ISSN	1932-7447
DOI	10.1021/acs.jpcc.9b09470
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Article ; Online: Spectroscopic Evidence for the Contribution of Holes to the Bleach of Cd-Chalcogenide Quantum Dots.

Grimaldi, Gianluca / Geuchies, Jaco J / van der Stam, Ward / du Fossé, Indy / Brynjarsson, Baldur / Kirkwood, Nicholas / Kinge, Sachin / Siebbeles, Laurens D A / Houtepen, Arjan J

Nano letters

2019 Volume 19, Issue 5, Page(s) 3002–3010

Abstract: In transient absorption (TA) measurements on Cd-chalcogenide quantum dots (QDs), the presence of a band-edge (BE) bleach signal is commonly attributed entirely to conduction-band electrons in the 1S(e) state, neglecting contributions from BE holes. While ...

Abstract	In transient absorption (TA) measurements on Cd-chalcogenide quantum dots (QDs), the presence of a band-edge (BE) bleach signal is commonly attributed entirely to conduction-band electrons in the 1S(e) state, neglecting contributions from BE holes. While this has been the accepted view for more than 20 years, and has often been used to distinguish electron and hole kinetics, the reason for the absence of a hole contribution to the BE-bleach has remained unclear. Here, we show with three independent experiments that holes do in fact have a significant impact on the BE-bleach of well-passivated Cd-chalcogenide QD samples. Transient absorption experiments on high photoluminescence quantum yield CdSe/CdS/ZnS core-shell-shell QDs clearly show an increase of the band-edge bleach as holes cool down to the band edge. The relative contribution of electron-to-hole bleach is 2:1, as predicted by theory. The same measurements on core-only CdSe QDs with a lower quantum yield do not show a contribution of holes to the band-edge bleach. We assign the lack of hole bleach to the presence of ultrafast hole trapping in samples with insufficient passivation of the QD surface. In addition, we show measurements of optical gain in core-shell-shell QD solutions, providing clear evidence of a significant hole contribution to the BE transient absorption signal. Finally, we present spectroelectrochemical measurements on CdTe QDs films, showing the presence of a BE-bleach for both electron and hole injections. The presence of a contribution of holes to the bleach in passivated Cd-chalcogenides QDs bears important implications for quantitative studies on optical gain as well as for TA determinations of carrier dynamics.
Language	English
Publishing date	2019-04-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1530-6992
ISSN (online)	1530-6992
DOI	10.1021/acs.nanolett.9b00164
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Article ; Online: Finding and Fixing Traps in II-VI and III-V Colloidal Quantum Dots: The Importance of Z-Type Ligand Passivation.

Kirkwood, Nicholas / Monchen, Julius O V / Crisp, Ryan W / Grimaldi, Gianluca / Bergstein, Huub A C / du Fossé, Indy / van der Stam, Ward / Infante, Ivan / Houtepen, Arjan J

Journal of the American Chemical Society

2018 Volume 140, Issue 46, Page(s) 15712–15723

Abstract: Energy levels in the band gap arising from surface states can dominate the optical and electronic properties of semiconductor nanocrystal quantum dots (QDs). Recent theoretical work has predicted that such trap states in II-VI and III-V QDs arise only ... ...

Abstract	Energy levels in the band gap arising from surface states can dominate the optical and electronic properties of semiconductor nanocrystal quantum dots (QDs). Recent theoretical work has predicted that such trap states in II-VI and III-V QDs arise only from two-coordinated anions on the QD surface, offering the hypothesis that Lewis acid (Z-type) ligands should be able to completely passivate these anionic trap states. In this work, we provide experimental support for this hypothesis by demonstrating that Z-type ligation is the primary cause of PL QY increase when passivating undercoordinated CdTe QDs with various metal salts. Optimized treatments with InCl
Language	English
Publishing date	2018-11-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3155-0
ISSN	1520-5126 ; 0002-7863
ISSN (online)	1520-5126
ISSN	0002-7863
DOI	10.1021/jacs.8b07783
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Article: Detailed immune monitoring of a pregnant woman with critical Covid-19

du Fossé, N A / Bronsgeest, K / Arbous, M S / Zlei, M / Myeni, S K / Kikkert, M / van Dongen, Jjm / Staal, Fjt / van der Hoorn, Mlp / van den Akker, T

J Reprod Immunol

Abstract	A primigravid woman with Covid-19 related respiratory insufficiency was admitted into a tertiary Intensive Care Unit at 23 3/7 weeks' gestation. Highly sensitive flow cytometry of peripheral leukocytes indicated significantly suppressed naïve T- and B-cell compartments. The suppressed immune cell responses led us keep the initially started administration of corticosteroids for fetal and maternal indication at a low dose. After three weeks her B-cell response peaked, SARS-CoV-2 was cleared and clinical improvement ensued a week later. At 28 weeks' gestation, a son of 1570 g was born by cesarean section. She was extubated two days postpartum and discharged from hospital 5.5 weeks postpartum.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #894079
Database	COVID19

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Article: Finding and Fixing Traps in II–VI and III–V Colloidal Quantum Dots: The Importance of Z-Type Ligand Passivation

Kirkwood, Nicholas / Monchen, Julius O. V / Crisp, Ryan W / Grimaldi, Gianluca / Bergstein, Huub A. C / du Fossé, Indy / van der Stam, Ward / Infante, Ivan / Houtepen, Arjan J

Journal of the American Chemical Society. 2018 Oct. 30, v. 140, no. 46

2018

Abstract	Energy levels in the band gap arising from surface states can dominate the optical and electronic properties of semiconductor nanocrystal quantum dots (QDs). Recent theoretical work has predicted that such trap states in II–VI and III–V QDs arise only from two-coordinated anions on the QD surface, offering the hypothesis that Lewis acid (Z-type) ligands should be able to completely passivate these anionic trap states. In this work, we provide experimental support for this hypothesis by demonstrating that Z-type ligation is the primary cause of PL QY increase when passivating undercoordinated CdTe QDs with various metal salts. Optimized treatments with InCl3 or CdCl2 afford a near-unity (>90%) photoluminescence quantum yield (PL QY), whereas other metal halogen or carboxylate salts provide a smaller increase in PL QY as a result of weaker binding or steric repulsion. The addition of non-Lewis acidic ligands (amines, alkylammonium chlorides) systematically gives a much smaller but non-negligible increase in the PL QY. We discuss possible reasons for this result, which points toward a more complex and dynamic QD surface. Finally we show that Z-type metal halide ligand treatments also lead to a strong increase in the PL QY of CdSe, CdS, and InP QDs and can increase the efficiency of sintered CdTe solar cells. These results show that surface anions are the dominant source of trap states in II–VI and III–V QDs and that passivation with Lewis acidic Z-type ligands is a general strategy to fix those traps. Our work also provides a method to tune the PL QY of QD samples from nearly zero up to near-unity values, without the need to grow epitaxial shells.
Keywords	Lewis acids ; amines ; anions ; cadmium chloride ; energy ; halogens ; ligands ; photoluminescence ; quantum dots ; solar cells
Language	English
Dates of publication	2018-1030
Size	p. 15712-15723.
Publishing place	American Chemical Society
Document type	Article
ZDB-ID	3155-0
ISSN	1520-5126 ; 0002-7863
ISSN (online)	1520-5126
ISSN	0002-7863
DOI	10.1021/jacs.8b07783
Database	NAL-Catalogue (AGRICOLA)

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