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Redirecting reproductive immunology research toward pregnancy as a period of temporary immune tolerance

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Abstract

Referring to two recent publications, we here propose that clinical reproductive immunology has for decades stagnated because reproductive medicine, including assisted reproduction (AR), has failed to accept embryo implantation as an immune system-driven process, dependent on establishment of maternal tolerance toward the implanting fetal semi-allograft (and complete allograft in cases of oocyte donation). Pregnancy represents a biologically unique period of temporary (to the period of gestation restricted) tolerance, otherwise only known in association with parasitic infections. Rather than investigating the immune pathways necessary to induce this rather unique state of tolerance toward the rapidly growing parasitic antigen load of the fetus, the field, instead, concentrated on irrelevant secondary immune phenomena (i.e., “immunological noise”). It, therefore, does not surprise that interesting recent research, offering new potential insights into maternal tolerance during pregnancy, was mostly published outside of the field of reproductive medicine. This research offers evidence for existence of inducible maternal tolerance pathways with the ability of improving maternal fecundity and, potentially, reducing such late pregnancy complications as premature labor and preeclampsia/eclampsia due to premature abatement of maternal tolerance. Increasing evidence also suggests that tolerance-inducing immune pathways are similar in successful pregnancy, successful organ transplantation and, likely also in the tolerance of “self” (i.e., prevention of autoimmunity). Identifying and isolating these pathways, therefore, may greatly benefit all three of these clinical areas, and research in reproductive immunology should be accordingly redirected.

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Authors’ contributions

NG conceived the concept for this manuscript and wrote the first draft. VAK and DHB contributed to revisions of the manuscript. All authors approved of the final manuscript.

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Authors and Affiliations

  1. The Center for Human Reproduction, 21 East 69th Street, New York, NY, 10021, USA

    Norbert Gleicher, Vitaly A. Kushnir & David H Barad

  2. Foundation for Reproductive Medicine, New York, NY, 10022, USA

    Norbert Gleicher & David H Barad

  3. Laboratory of Stem Cell Biology and Molecular Embryology, The Rockefeller University, New York, NY, 10065, USA

    Norbert Gleicher

  4. Department of Obstetrics and Gynecology, University of Vienna School of Medicine, 1090, Vienna, Austria

    Norbert Gleicher

  5. Department of Obstetrics and Gynecology, Wake Forest University, Winston Salem, NC, 27109, USA

    Vitaly A. Kushnir

Authors
  1. Norbert Gleicher
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  2. Vitaly A. Kushnir
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  3. David H Barad
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Corresponding author

Correspondence to Norbert Gleicher.

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Funding

No external funds were used in support of this manuscript.

Conflict of interest

NG, and DHB, are co-inventors on a number of pending and already awarded US patents claiming therapeutic benefits from androgen supplementation in women with low functional ovarian reserve (LFOR) and relating to the FMR1 gene in a diagnostic function in female fertility. Both receive royalties from Fertility Nutraceuticals, LLC, in which NG also holds shares. NG, DHB, and VAK also are co-inventors on three pending AMH-related patent applications. They report no conflicts with the reported manuscript.

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Capsule

We here propose that that induction of tolerance pathways is essential to establishment and maintenance of normal pregnancy.

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Gleicher, N., Kushnir, V.A. & Barad, D.H. Redirecting reproductive immunology research toward pregnancy as a period of temporary immune tolerance. J Assist Reprod Genet 34, 425–430 (2017). https://doi.org/10.1007/s10815-017-0874-x

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  • DOI: https://doi.org/10.1007/s10815-017-0874-x

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