Tacrolimus treatment for infertility related to maternal‐fetal immune interactions

Yamaguchi, Koushi

doi:10.1111/aji.13097

Cited by 13 publications

(13 citation statements)

References 113 publications

(161 reference statements)

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“…Currently, use of the new immunosuppressive agents tacrolimus and cyclosporine, which minimize immune rejection of transplanted organs, has been proposed as useful for infertile patients with immune overactivation [148,149]. When infertile patients with overactive immune conditions were carefully selected, tacrolimus was reported to improve the pregnancy outcome [149][150][151]. To support this approach, a common mTOR (mammalian target of rapamycin) inhibitor, sirolimus, which effectively prevents allograft rejection, was recently demonstrated to improve clinical pregnancy and live birth rates after repeated IVF therapy failures by reducing the Th17/Treg cell ratio [152].…”

Section: Topics Of Clinical Application Of Immune Therapymentioning

confidence: 99%

Promoting Roles of Embryonic Signals in Embryo Implantation and Placentation in Cooperation with Endocrine and Immune Systems

Fujiwara

Ono

Sato

et al. 2020

IJMS

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Embryo implantation in the uterus is an essential process for successful pregnancy in mammals. In general, the endocrine system induces sufficient embryo receptivity in the endometrium, where adhesion-promoting molecules increase and adhesion-inhibitory molecules decrease. Although the precise mechanisms remain unknown, it is widely accepted that maternal–embryo communications, including embryonic signals, improve the receptive ability of the sex steroid hormone-primed endometrium. The embryo may utilize repulsive forces produced by an Eph–ephrin system for its timely attachment to and subsequent invasion through the endometrial epithelial layer. Importantly, the embryonic signals are considered to act on maternal immune cells to induce immune tolerance. They also elicit local inflammation that promotes endometrial differentiation and maternal tissue remodeling during embryo implantation and placentation. Additional clarification of the immune control mechanisms by embryonic signals, such as human chorionic gonadotropin, pre-implantation factor, zona pellucida degradation products, and laeverin, will aid in the further development of immunotherapy to minimize implantation failure in the future.

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Section: Topics Of Clinical Application Of Immune Therapymentioning

confidence: 99%

Promoting Roles of Embryonic Signals in Embryo Implantation and Placentation in Cooperation with Endocrine and Immune Systems

Fujiwara

Ono

Sato

et al. 2020

IJMS

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“…When it comes to immunity and pregnancy, it is universally acknowledged that immune tolerance to the semi-allogeneic fetus is significantly rudimentary for a successful pregnancy. Abnormalities of endometrial immunity are involved in the pathogenesis of RIF ( 67 , 68 ). At present, research on the immune microenvironment in the endometrium of RIF during WOI is in full swing.…”

Section: Discussionmentioning

confidence: 99%

Deciphering the endometrial immune landscape of RIF during the window of implantation from cellular senescence by integrated bioinformatics analysis and machine learning

Zhao

Zhao²,

Jiang³

et al. 2022

Front. Immunol.

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Recurrent implantation failure (RIF) is an extremely thorny issue in in-vitro fertilization (IVF)-embryo transfer (ET). However, its intricate etiology and pathological mechanisms are still unclear. Nowadays, there has been extensive interest in cellular senescence in RIF, and its involvement in endometrial immune characteristics during the window of implantation (WOI) has captured scholars’ growing concerns. Therefore, this study aims to probe into the pathological mechanism of RIF from cellular senescence and investigate the correlation between cellular senescence and endometrial immune characteristics during WOI based on bioinformatics combined with machine learning strategy, so as to elucidate the underlying pathological mechanisms of RIF and to explore novel treatment strategies for RIF. Firstly, the gene sets of GSE26787 and GSE111974 from the Gene Expression Omnibus (GEO) database were included for the weighted gene correlation network analysis (WGCNA), from which we concluded that the genes of the core module were closely related to cell fate decision and immune regulation. Subsequently, we identified 25 cellular senescence-associated differentially expressed genes (DEGs) in RIF by intersecting DEGs with cellular senescence-associated genes from the Cell Senescence (CellAge) database. Moreover, functional enrichment analysis was conducted to further reveal the specific molecular mechanisms by which these molecules regulate cellular senescence and immune pathways. Then, eight signature genes were determined by the machine learning method of support vector machine-recursive feature elimination (SVM-RFE), random forest (RF), and artificial neural network (ANN), comprising LATS1, EHF, DUSP16, ADCK5, PATZ1, DEK, MAP2K1, and ETS2, which were also validated in the testing gene set (GSE106602). Furthermore, distinct immune microenvironment abnormalities in the RIF endometrium during WOI were comprehensively explored and validated in GSE106602, including infiltrating immunocytes, immune function, and the expression profiling of human leukocyte antigen (HLA) genes and immune checkpoint genes. Moreover, the correlation between the eight signature genes with the endometrial immune landscape of RIF was also evaluated. After that, two distinct subtypes with significantly distinct immune infiltration characteristics were identified by consensus clustering analysis based on the eight signature genes. Finally, a “KEGG pathway–RIF signature genes–immune landscape” association network was constructed to intuitively uncover their connection. In conclusion, this study demonstrated that cellular senescence might play a pushing role in the pathological mechanism of RIF, which might be closely related to its impact on the immune microenvironment during the WOI phase. The exploration of the molecular mechanism of cellular senescence in RIF is expected to bring new breakthroughs for disease diagnosis and treatment strategies.

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“…In contrast, Th2 dominance is required for successful implantation and pregnancy. Recurrent implantation failure and pregnancy loss were negatively correlated with Th1 cell numbers [ 8 ]. In addition, NK cells increased in number at the decidua in a case of chromosome-normal abortion [ 9 ].…”

Section: Discussionmentioning

confidence: 99%

Successful Pregnancy in a Case of Behçet’s Disease after Treatment with Prednisolone

Nishii

Yamaguchi

Amita

et al. 2020

Case Reports in Obstetrics and Gynecology

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A 34-year-old woman (gravida 1, para 0) visited the Division of Reproductive Medicine/National Center for Child Health and Development due to infertility; she had also been suffering from incompletely treated genital ulcers and stomatitis for 10 years. This case was diagnosed as an incomplete-type Behçet’s disease (BD) at the Department of Maternal-Fetal Biology/National Center for Child Health and Development. Since no apparent abnormality was found in the general infertility test, artificial insemination with the husband’s semen (AIH) was performed for the patient with unexplained infertility, which failed. However, after treating BD with prednisolone, chronic inflammation (stomatitis and genital ulcer) and immunological abnormalities (Th2 and NK cell activity) improved, and conception was possible by AIH. Thus, prednisolone administration may have induced immune tolerance in the patient with BD, which may have contributed to the success of AIH.

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Tacrolimus treatment for infertility related to maternal‐fetal immune interactions

Cited by 13 publications

References 113 publications

Promoting Roles of Embryonic Signals in Embryo Implantation and Placentation in Cooperation with Endocrine and Immune Systems

Promoting Roles of Embryonic Signals in Embryo Implantation and Placentation in Cooperation with Endocrine and Immune Systems

Deciphering the endometrial immune landscape of RIF during the window of implantation from cellular senescence by integrated bioinformatics analysis and machine learning

Successful Pregnancy in a Case of Behçet’s Disease after Treatment with Prednisolone

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