Altered helper T cell-mediated immune responses in male mice conceived through in vitro fertilization

Karimi, Hiwa; Mahdavi, Pooya; Fakhari, Shohreh; Faryabi, Mohammad Reza; Esmaeili, Parisa; Banafshi, Omid; Mohammadi, Ebrahim; Fathi, Fardin; Mokarizadeh, Aram

doi:10.1016/j.reprotox.2017.03.005

Cited by 10 publications

(6 citation statements)

References 34 publications

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“…Another reason may be the variety of genetic backgrounds. In addition to clinical studies, animal studies identified similar alterations in T H cell-mediated immune responses in ART-conceived mice [ 5 , 6 ]. Compared with NC mice, the ART group exhibited higher IL-4 serum levels and promoted T H 2 immune responses in fresh embryo transfer, consistent with our findings.…”

Section: Discussionmentioning

confidence: 99%

“…Alterations to children’s immune systems after ART treatment have gained increasing traction in animal and human studies. ART conceived mice exhibited less efficient immune responses to vaccines and promoted T helper (T H ) 2 immune responses [ 5 , 6 ]. ART conceived children were associated with a high prevalence of immune-related diseases, including metabolic disorders and allergic diseases [ 7 – 11 ].…”

Section: Introductionmentioning

confidence: 99%

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The altered immunological status of children conceived by assisted reproductive technology

Bian

et al. 2021

Reprod Biol Endocrinol

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The altered immunological status of children conceived by assisted reproductive technology

Bian

et al. 2021

Reprod Biol Endocrinol

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“…Indeed, in vitro fertilization techniques dysregulated genes encoding proteins that play a role in immune regulation in placental tissues [ 85 ]. A study in ART-conceived mice also revealed disturbances in the TH1/TH2/TH17 balance [ 86 ], while another highlighted an altered helper T cell-mediated immune response [ 87 ]. It would be worth assessing whether the immune imbalance we observed in the cells of ART children shifts with age.…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Analysis of DNA Methylation in Buccal Cells of Children Conceived through IVF and ICSI

Ducreux

Frappier

Bruno

et al. 2021

Genes

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Early life periconceptional exposures during assisted reproductive technology (ART) procedures could alter the DNA methylation profiles of ART children, notably in imprinted genes and repetitive elements. At the genome scale, DNA methylation differences have been reported in ART conceptions at birth, but it is still unclear if those differences remain at childhood. Here, we performed an epigenome-wide DNA methylation association study using Illumina InfiniumEPIC BeadChip to assess the effects of the mode of conception on the methylome of buccal cells from 7- to 8-year-old children (48 children conceived after ART or naturally (control, CTL)) and according to the embryo culture medium in which they were conceived. We identified 127 differentially methylated positions (DMPs) and 16 differentially methylated regions (DMRs) (FDR < 0.05) with low delta beta differences between the two groups (ART vs. CTL). DMPs were preferentially located inside promoter proximal regions and CpG islands and were mostly hypermethylated with ART. We highlighted that the use of distinct embryo culture medium was not associated with DNA methylation differences in childhood. Overall, we bring additional evidence that children conceived via ART display limited genome-wide DNA methylation variation compared with those conceived naturally.

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“…Subsequently, zygotes were quickly washed three times in KOSM media and then cultured in KSOM. The mouse embryo culture continued till Day3.5 in an incubator set at 37°C and 5% CO 2 ( Dumollard et al, 2008 ; Karimi et al, 2017 ; Azizi et al, 2020 ).…”

Section: Manuscript Formattingmentioning

confidence: 99%

Effect of Sperm Cryopreservation on miRNA Expression and Early Embryonic Development

Zhang

et al. 2021

Front. Cell Dev. Biol.

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Although sperm preservation is a common means of personal fertility preservation, its effects on embryonic development potential need further investigation. The purpose of this study was to identify key microRNA (miRNA) in cryopreserved sperm and determine the changes of these miRNAs and their target genes during embryonic development using cryopreserved sperm. Moreover, the embryonic development potential of cryopreserved sperm was estimated in assisted reproductive technology (ART), where key miRNAs and target genes were validated in sperm and subsequent embryos. Clinical data of embryonic development from cryopreserved sperm indicated a significant decrease in fertilization rate in both in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cases, as well as a reduction in blastocyst formation rate in ICSI cases. Meanwhile there was a significant increase in blocked embryo ratio of Day1, Day2, and Day3.5 embryos when frozen-thawed mouse sperm was used, compared with fresh mouse sperm, suggesting a potential negative effect of sperm cryopreservation on embryonic development. From frozen-thawed and fresh sperm in humans and mice, respectively, 21 and 95 differentially expressed miRNAs (DEmiRs) were detected. miR-148b-3p were downregulated in both human and mouse frozen-thawed sperm and were also decreased in embryos after fertilization using cryopreserved sperm. Target genes of miR-148b-3p, Pten, was identified in mouse embryos using quantitative real-time PCR (qRT-PCR) and Western blot (WB). In addition, common characters of cryopreservation of mouse oocytes compared with sperm were also detected; downregulation of miR-148b-3p was also confirmed in cryopreserved oocytes. In summary, our study suggested that cryopreservation of sperm could change the expression of miRNAs, especially the miR-148b-3p across humans and mice, and may further affect fertilization and embryo development by increasing the expression of Pten. Moreover, downregulation of miR-148b-3p induced by cryopreservation was conserved in mouse gametes.

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Altered helper T cell-mediated immune responses in male mice conceived through in vitro fertilization

Cited by 10 publications

References 34 publications

The altered immunological status of children conceived by assisted reproductive technology

The altered immunological status of children conceived by assisted reproductive technology

Genome-Wide Analysis of DNA Methylation in Buccal Cells of Children Conceived through IVF and ICSI

Effect of Sperm Cryopreservation on miRNA Expression and Early Embryonic Development

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