The altered immunological status of children conceived by assisted reproductive technology

Abstract Background With the increased use of assisted reproductive technology (ART), assessing the potential health risks of children conceived on ART important to public health. Most research in this area has focused on the effects of ART on perinatal, metabolic, and oncological risks in children....

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Autores principales: Xin Xu, Han Wu, Yuehong Bian, Linlin Cui, Yuanyuan Man, Zhao Wang, Xin Zhang, Changming Zhang, Ling Geng
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Lenguaje:EN
Publicado: BMC 2021
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spelling oai:doaj.org-article:f9c9eb6a53194823b47556d1d283dff42021-11-28T12:37:46ZThe altered immunological status of children conceived by assisted reproductive technology10.1186/s12958-021-00858-21477-7827https://doaj.org/article/f9c9eb6a53194823b47556d1d283dff42021-11-01T00:00:00Zhttps://doi.org/10.1186/s12958-021-00858-2https://doaj.org/toc/1477-7827Abstract Background With the increased use of assisted reproductive technology (ART), assessing the potential health risks of children conceived on ART important to public health. Most research in this area has focused on the effects of ART on perinatal, metabolic, and oncological risks in children. Although an increased risk of immune-related diseases has been reported in children born after ART, there are no studies on the immunological status of these children. This study aimed to evaluate the impact of different embryo transfer methods and fertilization strategies on the immune status of the offspring. Methods A total of 69 children born to women treated with ART and a matched control group of 17 naturally conceived (NC) children, all aged from 3 to 6 years, were recruited in the reproductive hospital affiliated to Shandong University. The frequency of immune cells in the peripheral blood was assayed using flow cytometry; plasma cytokine levels were determined by multiplex cytokine immunoassay with human cytokine magnetic beads. Results Compared to children born after natural conception, children born after ART had elevated interferon-γ (IFN-γ) levels, regardless of embryo transfer and fertilization strategies. Children in the fresh-embryo transfer group had significantly higher IL-4 levels and a lower ratio of IFN-γ to IL-4 than those in the NC group ((P = 0.004, 10.41 ± 5.76 pg/mL vs 18.40 ± 7.01 pg/mL, P = 0.023, 1.00 ± 0.48 vs 0.67 ± 0.32, respectively). Similar results were shown in either the in vitro fertilization (IVF) group or the intra-cytoplasmic sperm injection (ICSI) group (P < 0.05 and P = 0.08 for IVF; P < 0.05 and P < 0.05 for ICSI, respectively). These alterations in IL-4 concentrations and the ratio of IFN-γ to IL-4 were statistically significantly correlated with supra-physical E2 (estradiol) levels on the day of hCG administration (R = 0.502, P = 0.017; R = − 0.537, P = 0.010, respectively). Consistently, the frozen embryo transfer did not result in alterations of these immune indicators in the offspring. Overall, there were no significant differences between the ART group and NC group in the frequencies of T cells, B cells, natural killer (NK) cells, CD4+T cells, CD8+T cells, T helper (TH)1 cells, TH17 cells, and regulatory T (Treg) cells and cytokine levels of IL-10 and IL-17a (all P > 0.05). Conclusions Immunological alterations existed in children born after the use of ART. The elevated E2 levels before embryo implantation contributed to the increased IL-4 levels in children conceived by fresh embryo transfer. The assessment of immunological alteration is of importance to children conceived by ART for early monitoring and intervention.Xin XuHan WuYuehong BianLinlin CuiYuanyuan ManZhao WangXin ZhangChangming ZhangLing GengBMCarticleAssisted reproductive technologyChildrenImmune systemInterleukin-4Interferon-gammaGynecology and obstetricsRG1-991ReproductionQH471-489ENReproductive Biology and Endocrinology, Vol 19, Iss 1, Pp 1-8 (2021)
institution DOAJ
collection DOAJ
language EN
topic Assisted reproductive technology
Children
Immune system
Interleukin-4
Interferon-gamma
Gynecology and obstetrics
RG1-991
Reproduction
QH471-489
spellingShingle Assisted reproductive technology
Children
Immune system
Interleukin-4
Interferon-gamma
Gynecology and obstetrics
RG1-991
Reproduction
QH471-489
Xin Xu
Han Wu
Yuehong Bian
Linlin Cui
Yuanyuan Man
Zhao Wang
Xin Zhang
Changming Zhang
Ling Geng
The altered immunological status of children conceived by assisted reproductive technology
description Abstract Background With the increased use of assisted reproductive technology (ART), assessing the potential health risks of children conceived on ART important to public health. Most research in this area has focused on the effects of ART on perinatal, metabolic, and oncological risks in children. Although an increased risk of immune-related diseases has been reported in children born after ART, there are no studies on the immunological status of these children. This study aimed to evaluate the impact of different embryo transfer methods and fertilization strategies on the immune status of the offspring. Methods A total of 69 children born to women treated with ART and a matched control group of 17 naturally conceived (NC) children, all aged from 3 to 6 years, were recruited in the reproductive hospital affiliated to Shandong University. The frequency of immune cells in the peripheral blood was assayed using flow cytometry; plasma cytokine levels were determined by multiplex cytokine immunoassay with human cytokine magnetic beads. Results Compared to children born after natural conception, children born after ART had elevated interferon-γ (IFN-γ) levels, regardless of embryo transfer and fertilization strategies. Children in the fresh-embryo transfer group had significantly higher IL-4 levels and a lower ratio of IFN-γ to IL-4 than those in the NC group ((P = 0.004, 10.41 ± 5.76 pg/mL vs 18.40 ± 7.01 pg/mL, P = 0.023, 1.00 ± 0.48 vs 0.67 ± 0.32, respectively). Similar results were shown in either the in vitro fertilization (IVF) group or the intra-cytoplasmic sperm injection (ICSI) group (P < 0.05 and P = 0.08 for IVF; P < 0.05 and P < 0.05 for ICSI, respectively). These alterations in IL-4 concentrations and the ratio of IFN-γ to IL-4 were statistically significantly correlated with supra-physical E2 (estradiol) levels on the day of hCG administration (R = 0.502, P = 0.017; R = − 0.537, P = 0.010, respectively). Consistently, the frozen embryo transfer did not result in alterations of these immune indicators in the offspring. Overall, there were no significant differences between the ART group and NC group in the frequencies of T cells, B cells, natural killer (NK) cells, CD4+T cells, CD8+T cells, T helper (TH)1 cells, TH17 cells, and regulatory T (Treg) cells and cytokine levels of IL-10 and IL-17a (all P > 0.05). Conclusions Immunological alterations existed in children born after the use of ART. The elevated E2 levels before embryo implantation contributed to the increased IL-4 levels in children conceived by fresh embryo transfer. The assessment of immunological alteration is of importance to children conceived by ART for early monitoring and intervention.
format article
author Xin Xu
Han Wu
Yuehong Bian
Linlin Cui
Yuanyuan Man
Zhao Wang
Xin Zhang
Changming Zhang
Ling Geng
author_facet Xin Xu
Han Wu
Yuehong Bian
Linlin Cui
Yuanyuan Man
Zhao Wang
Xin Zhang
Changming Zhang
Ling Geng
author_sort Xin Xu
title The altered immunological status of children conceived by assisted reproductive technology
title_short The altered immunological status of children conceived by assisted reproductive technology
title_full The altered immunological status of children conceived by assisted reproductive technology
title_fullStr The altered immunological status of children conceived by assisted reproductive technology
title_full_unstemmed The altered immunological status of children conceived by assisted reproductive technology
title_sort altered immunological status of children conceived by assisted reproductive technology
publisher BMC
publishDate 2021
url https://doaj.org/article/f9c9eb6a53194823b47556d1d283dff4
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