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Myeloid-Derived Suppressor Cells Are Regulated by Estradiol and Are a Predictive Marker for IVF Outcome
In vitro fertilization (IVF) is an effective means to treat infertility, but the pregnancy rate is still unsatisfactory and reliable markers to predict pregnancy outcome are ill-defined. Myeloid-derived suppressor cell (MDSC) are critically involved in decisions related to the acceptance or rejectio...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6682648/ https://www.ncbi.nlm.nih.gov/pubmed/31417498 http://dx.doi.org/10.3389/fendo.2019.00521 |
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author | Hu, Cong Zhen, Yu Pang, Bo Lin, Xiuying Yi, Huanfa |
author_facet | Hu, Cong Zhen, Yu Pang, Bo Lin, Xiuying Yi, Huanfa |
author_sort | Hu, Cong |
collection | PubMed |
description | In vitro fertilization (IVF) is an effective means to treat infertility, but the pregnancy rate is still unsatisfactory and reliable markers to predict pregnancy outcome are ill-defined. Myeloid-derived suppressor cell (MDSC) are critically involved in decisions related to the acceptance or rejection of foreign fetal antigens by the maternal immune system. However, factors that regulate peripheral blood MDSC during pre-pregnancy are poorly defined. Thus, the goal of this study was to assess the relationships among serum estradiol (E(2)) and endothelial growth factor (VEGF) levels, MDSC ratios, and pregnancy outcome associated with IVF. Patients undergoing IVF treatment (n = 54) were recruited from January to June 2018. Levels of E(2) and VEGF were measured by ELISA, MDSC ratios among peripheral blood mononuclear cells (PBMC) were detected by flow cytometry, and the crosstalk among these parameters was analyzed. A receiver operating characteristic curve (ROC) of MDSC levels was plotted to assess this measure as an independent predictive factor for pregnancy. In addition, we analyzed the possible involvement of molecular pathways by bioinformatics. When E(2) levels were <4,000 pg/ml, MDSC proportion was positively correlated with serum E(2) and VEGF levels. However, when E(2) levels were >4,000 pg/ml, MDSC ratio and VEGF levels were negatively correlated with E(2). A ROC curve revealed that the percentage of MDSC had better sensitivity and specificity at a concentration of 8.22% (0.875 and 0.75, respectively; area under the curve (AUC) = 0.859) to predict pregnancy success, based on multiple logistic regression analysis. Furthermore, we found 12 target genes of E(2) and VEGF, and also functional genes related to MDSC, indicating potential protein–protein interactions underlying these associations. In summary, we showed that E(2), depending on its concentration, might play a dichotomous role in influencing the MDSC proportion by regulating VEGF. In IVF patients, an increased MDSC ratio among PBMC was highly correlated with elevated pregnancy rates, independent of the effects of E(2), which might provide new insight into immune-related miscarriage and IVF failure. |
format | Online Article Text |
id | pubmed-6682648 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-66826482019-08-15 Myeloid-Derived Suppressor Cells Are Regulated by Estradiol and Are a Predictive Marker for IVF Outcome Hu, Cong Zhen, Yu Pang, Bo Lin, Xiuying Yi, Huanfa Front Endocrinol (Lausanne) Endocrinology In vitro fertilization (IVF) is an effective means to treat infertility, but the pregnancy rate is still unsatisfactory and reliable markers to predict pregnancy outcome are ill-defined. Myeloid-derived suppressor cell (MDSC) are critically involved in decisions related to the acceptance or rejection of foreign fetal antigens by the maternal immune system. However, factors that regulate peripheral blood MDSC during pre-pregnancy are poorly defined. Thus, the goal of this study was to assess the relationships among serum estradiol (E(2)) and endothelial growth factor (VEGF) levels, MDSC ratios, and pregnancy outcome associated with IVF. Patients undergoing IVF treatment (n = 54) were recruited from January to June 2018. Levels of E(2) and VEGF were measured by ELISA, MDSC ratios among peripheral blood mononuclear cells (PBMC) were detected by flow cytometry, and the crosstalk among these parameters was analyzed. A receiver operating characteristic curve (ROC) of MDSC levels was plotted to assess this measure as an independent predictive factor for pregnancy. In addition, we analyzed the possible involvement of molecular pathways by bioinformatics. When E(2) levels were <4,000 pg/ml, MDSC proportion was positively correlated with serum E(2) and VEGF levels. However, when E(2) levels were >4,000 pg/ml, MDSC ratio and VEGF levels were negatively correlated with E(2). A ROC curve revealed that the percentage of MDSC had better sensitivity and specificity at a concentration of 8.22% (0.875 and 0.75, respectively; area under the curve (AUC) = 0.859) to predict pregnancy success, based on multiple logistic regression analysis. Furthermore, we found 12 target genes of E(2) and VEGF, and also functional genes related to MDSC, indicating potential protein–protein interactions underlying these associations. In summary, we showed that E(2), depending on its concentration, might play a dichotomous role in influencing the MDSC proportion by regulating VEGF. In IVF patients, an increased MDSC ratio among PBMC was highly correlated with elevated pregnancy rates, independent of the effects of E(2), which might provide new insight into immune-related miscarriage and IVF failure. Frontiers Media S.A. 2019-07-30 /pmc/articles/PMC6682648/ /pubmed/31417498 http://dx.doi.org/10.3389/fendo.2019.00521 Text en Copyright © 2019 Hu, Zhen, Pang, Lin and Yi. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Endocrinology Hu, Cong Zhen, Yu Pang, Bo Lin, Xiuying Yi, Huanfa Myeloid-Derived Suppressor Cells Are Regulated by Estradiol and Are a Predictive Marker for IVF Outcome |
title | Myeloid-Derived Suppressor Cells Are Regulated by Estradiol and Are a Predictive Marker for IVF Outcome |
title_full | Myeloid-Derived Suppressor Cells Are Regulated by Estradiol and Are a Predictive Marker for IVF Outcome |
title_fullStr | Myeloid-Derived Suppressor Cells Are Regulated by Estradiol and Are a Predictive Marker for IVF Outcome |
title_full_unstemmed | Myeloid-Derived Suppressor Cells Are Regulated by Estradiol and Are a Predictive Marker for IVF Outcome |
title_short | Myeloid-Derived Suppressor Cells Are Regulated by Estradiol and Are a Predictive Marker for IVF Outcome |
title_sort | myeloid-derived suppressor cells are regulated by estradiol and are a predictive marker for ivf outcome |
topic | Endocrinology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6682648/ https://www.ncbi.nlm.nih.gov/pubmed/31417498 http://dx.doi.org/10.3389/fendo.2019.00521 |
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