A semen-based stimulation method to analyze cytokine production by uterine CD56bright natural killer cells in women with recurrent pregnancy loss

Taima, Ayako; Fukui, Atsushi; Yamaya, Ayano; Yokota, Megumi; Fukuhara, Rie; Yokoyama, Yoshihiko

doi:10.1016/j.jri.2020.103206

Cited by 4 publications

(3 citation statements)

References 35 publications

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“…Another major aspect of the present study was the further comparison of levels of immune mediators in uterine fluid from the secretory phase of the menstrual cycle prior to oocyte retrieval between women that achieved a clinical pregnancy or not. Recently, endometrial immune transcriptional profiling has been proposed as an innovative tool to test the local endometrial functioning ( Lédée et al, 2020 ), based on the idea that alterations in cytokine pattern at the feto–maternal interface could impact on the establishment and maintenance of pregnancy ( Franasiak and Scott, 2017 ; Taima et al , 2020 ). Boomsma et al (2009) demonstrated that multiplex immunoassay of aspirated uterine secretions offers a noninvasive method to characterize the endometrial in vivo milieu, providing the simultaneous detection of different mediators in a small volume.…”

Section: Discussionmentioning

confidence: 99%

Uterine fluid cytokine/chemokine levels of women undergoing ART with and without oral Vitamin D supplementation

Cermisoni

Reschini

Piccinni

et al. 2022

Human Reproduction Open

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STUDY QUESTION Is oral Vitamin D supplementation able to modify the intrauterine milieu in terms of cytokine/chemokine pattern? SUMMARY ANSWER No significant differences were detected in cytokine and chemokine levels in endometrial secretions between patients undergoing ART with or without Vitamin D supplementation. WHAT IS KNOWN ALREADY Cytokines and chemokines secreted into the intrauterine environment are fundamental for the molecular crosstalk between the endometrium and the preimplantation embryo. Whether Vitamin D can regulate these mediators in the endometrial environment is still unclear. STUDY DESIGN, SIZE, DURATION This study was an analysis of a secondary outcome from the Supplementation Of Vitamin D And Reproductive Outcomes clinical trial, a multi-center randomized double-blinded trial designed to explore the effects of Vitamin D replacement in insufficient women with Vitamin D levels below 30 ng/ml undergoing autologous ART cycles. Uterine fluid samples were collected from both patients supplemented with Vitamin D (n = 17) and from the placebo group (n = 32). PARTICIPANTS/MATERIALS, SETTING, METHODS Based on cutoff points for Vitamin D insufficiency (20–29.9 ng/mL) or deficiency (<20 ng/mL), 67% of patients in the study were insufficient, and 33% deficient, in Vitamin D, although they were considered together for the analysis. Women received a single dose of 600,000 IU 25-hydroxyvitamin D or placebo from 2 to 12 weeks before oocyte retrieval. Inclusion criteria were female age 18-39 years, with a BMI between 18 and 25 Kg/m2. Serum 25-hydroxyvitamin D was assessed at the time of hCG administration. Uterine fluid samples were collected during the secretory phase of the menstrual cycle preceding oocyte retrieval. The quantitative determination of 27 cytokines in endometrial secretion samples was performed by using a multiplex immunoassay. MAIN RESULTS AND THE ROLE OF CHANCE Uterine fluid samples were collected after a median (range) of 21 (12–41) days after the oral Vitamin D supplementation. Both the supplemented and placebo groups had Vitamin D serum levels below 30 ng/ml at baseline/time of randomization ((median 23.4 ng/ml (IQR 19.5–28.4) and 23.4 ng/ml (17.8–25.9), respectively). At time of hCG administration, serum Vitamin D in supplemented subjects was significantly raised compared to the placebo group ((median 52.9 ng/ml (interquartile range 40.7–64.1) and 24.6 ng/ml (19.3–29.2), respectively, p < 0.001). Our data revealed no significant differences in uterine fluid cytokine/chemokine composition of Vitamin D-supplemented women compared with the placebo group. This finding remained when the concentrations of all mediators studied were normalized to total protein. In a further analysis, no significant differences were found in the content of cytokines/chemokines in uterine fluid from women who conceived (n = 19) compared with the non-pregnant group (n = 30). LIMITATIONS, REASONS FOR CAUTION Using a randomized study design (a single dose of 600,000 IU 25-hydroxyvitamin D versus placebo), we found no significant differences between groups. However, we cannot exclude that any benefit of Vitamin D supplementation may be specific for some subgroups of patients, such as those with an imbalance of T-helper 1 and T-helper 2 cell populations. The uterine secretions were collected during the menstrual cycle that preceded oocyte retrieval, therefore it is possible the uterine fluid collection and analysis in the same cycle as the embryo transfer might have resulted in different conclusions. Moreover, the small sample size could limit the power of the study. WIDER IMPLICATIONS OF THE FINDINGS Our analysis of the uterine secretome profiling failed to show any significant difference in endometrial cytokine/chemokine patterns between women with oral Vitamin D supplementation and the placebo group. Vitamin D may act on the uterine environment through a different mechanism. STUDY FUNDING/COMPETING INTEREST(S) The study was funded by the Italian Ministry of Health following peer review in the competitive “Bando di Ricerca Finalizzata e Giovani Ricercatori 2013” with reference code RF-2013-02358757. The authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER EudraCT registration number: 2015-004233-27.

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Section: Discussionmentioning

confidence: 99%

Uterine fluid cytokine/chemokine levels of women undergoing ART with and without oral Vitamin D supplementation

Cermisoni

Reschini

Piccinni

et al. 2022

Human Reproduction Open

View full text Add to dashboard Cite

show abstract

“…Another major nding of the present study was the comparison of levels of immune mediators detected in uterine uid from the secretory phase of the menstrual cycle prior to oocyte retrieval between women that achieved a clinical pregnancy or not. Recently, the endometrial immune transcriptional pro ling has been proposed as an innovative tool to test the local endometrial functioning [33] based on the idea that alterations in cytokine pattern at the feto-maternal interface could impact on the establishment and maintenance of pregnancy [34,35]. Boomsa and colleagues demonstrated that the multiplex immunoassays of aspirated uterine secretions offer a non-invasive method to characterize the endometrial in vivo milieu, providing the simultaneously detection of different mediators in a small volume [15].…”

Section: Discussionmentioning

confidence: 99%

Oral Vitamin D Supplementation does not Impact Cytokine Levels in Uterine Fluid of Women Undergoing Assisted Reproduction Technology (ART)

Cermisoni

Reschini

Piccinni

et al. 2021

Preprint

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Background: Cytokines and chemokines, secreted in the intrauterine environment, are fundamental for the molecular crosstalk between endometrium and preimplantation embryo. Whether Vitamin D can have a beneficial effect on endometrial district and immune cells is still unclear. To fill this gap, the aim of this study was to explore if Vitamin D supplementation can act on intrauterine milieu as immuno-modulator. Methods: We present a report of a secondary outcome from the SUNDRO clinical trial, a multi-center randomized double-blinded trial aimed to explore the effects of Vitamin D replacement (a single dose of 600,000 IU of 25-hydroxy Vitamin D or placebo) in insufficient women undergoing autologous ART cycles. Inclusion criteria were female age between 18-39 years, with body mass index between 18 and 25 Kg/m2. Uterine fluid samples were collected during the secretory phase of the menstrual cycle that proceeded the oocyte retrieval. The quantitative determination of twenty-seven cytokines in endometrial secretion samples was performed by using a multiplex immunoassay.Results: Forty-nine uterine fluid samples (UF) were collected during the secretory phase of the menstrual cycle prior to oocyte retrieval. Our data revealed no differences in UF composition of Vitamin D supplemented women (n=17) compared with the placebo group (n=32), also when protein normalization was performed. In addition, no significant differences were found in mediators relative content of UFs from women who conceived (n=19) compared with the non-pregnant group (n=30). Conclusions: The explored in vivo vitamin D replacement regimen is unlikely to directly influence the cytokine and chemokine endometrial milieu. EudraCT registration number: 2015-004233-27.

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“…Based on this study, TGF- β and activin in seminal plasma may affect the function of cervical immune cells after coitus [ 10 ]. Taima et al showed that the production of inflammatory cytokines by endometrial NK cells is regulated by seminal plasma exposure, indicating immune compatibility between semen and endometrium [ 11 ]. Seminal plasma destroys free radicals with antioxidant factors such as vitamin C, carnitine, tyrosine, uric acid, glutathione peroxidase, and pyridoxine [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Impact of Vitamin C on Gene Expression Profile of Inflammatory and Anti-Inflammatory Cytokines in the Male Partners of Couples with Recurrent Pregnancy Loss

Fesahat

Norouzi

Seifati

et al. 2022

International Journal of Inflammation

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Immune system disorders and increased inflammation in the male reproductive system can lead to fetal risk in the early stages of development and implantation. Antioxidants such as vitamin C can play a protective role against sperm inflammatory reactions. This study aimed to evaluate the effect of vitamin C on the expression of inflammatory and anti-inflammatory cytokine genes in the male partners of couples with recurrent pregnancy loss. In this randomized clinical trial, twenty male partners of couples with RPL were examined for sperm parameters and expression profile of some inflammatory and anti-inflammatory cytokine genes before and after treatment with vitamin C. There was a statistically significant higher rate of normal morphology and sperm concentration in each patient before and after treatment with vitamin C p ≤ 0.05 . The mRNA levels of interleukin 6 and tumor necrosis factor-alpha were significantly decreased in the sperm of patients after treatment with vitamin C compared to before treatment. In contrast, the gene expression levels of interleukin 4 and transforming growth factor-beta showed a significant increase in the sperm of patients after treatment with vitamin C. Oral daily administration of vitamin C may be effective in the fertility potential of male partners of couples with RPL not only through the improvement of the sperm parameters but also by modulating the expression profile of inflammatory and anti-inflammatory genes. Further studies on protein levels are needed to clarify the role of TNF-⍺ and IFN-γ as a prognostic value in evaluating the recurrent abortion risk in infertile male partners. This trial is registered with IRCT20180312039059N1.

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A semen-based stimulation method to analyze cytokine production by uterine CD56bright natural killer cells in women with recurrent pregnancy loss

Cited by 4 publications

References 35 publications

Uterine fluid cytokine/chemokine levels of women undergoing ART with and without oral Vitamin D supplementation

Uterine fluid cytokine/chemokine levels of women undergoing ART with and without oral Vitamin D supplementation

Oral Vitamin D Supplementation does not Impact Cytokine Levels in Uterine Fluid of Women Undergoing Assisted Reproduction Technology (ART)

Impact of Vitamin C on Gene Expression Profile of Inflammatory and Anti-Inflammatory Cytokines in the Male Partners of Couples with Recurrent Pregnancy Loss

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