bims-reprim Biomed News
on Reproductive immunology
Issue of 2022‒01‒23
eight papers selected by
Iva Filipovic
Karolinska Institutet
  1. CD200S-positive granulated lymphoid cells in endometrium appear to be CD56-positive uterine NK cells.
  2. Maternal-fetal immune responses in pregnant women infected with SARS-CoV-2.
  3. Antiphospholipid antibodies do not cause retargeting of placental extracellular vesicles in the maternal body.
  4. Immune landscape of human placental villi using single-cell analysis.
  5. Studies reveal dangers of SARS-CoV-2 infection in pregnancy.
  6. Foreword: Uterine Transplantation in Pregnancy.
  7. The role of endometrial staining for CD138 as a marker of chronic endometritis in predicting live birth.
  8. A blood test to predict pre‑eclampsia.
  1. J Reprod Immunol. 2022 Jan 14. pii: S0165-0378(22)00005-5. [Epub ahead of print]150 103477
    CD200S-positive granulated lymphoid cells in endometrium appear to be CD56-positive uterine NK cells.
    David A Clark, Amir Reihani, Jorge L Arredondo, Kjetil Ask, Warren G Foster.
      The eutopic secretory phase endometrium in endometriosis overproduces and releases a soluble immunosuppressive CD200 molecule (CD200L) and is populated by stromal cells that contain a truncated CD200 (CD200S) that promotes a proinflammatory environment. The CD200S+ cell population persists when pregnancy occurs and are abundant in the early pregnancy decidua of women with missed abortion. In the present study, CD200S+, CD56+, and CD68+ cells were enumerated in formalin-fixed paraffin-embedded tissue sections from women with endometriosis and non-endometriosis controls. CD200S+ cells were more numerous than CD68+ macrophages and were similar in number and location to CD56bright endometrial NK cells. In some endometria, there was an additional population of CD200S- CD56+ NK cells. In ectopic endometrial peritoneal deposits and in ectopic myometrial deposits (adenomyosis), CD200S+ cells were less frequent, consistent with the known paucity of CD56+ NK cells in sites of ectopic deposits. CD200S+ cell frequency was greater in stroma surrounding the smaller ectopic cystic deposits. Dual immunofluorescent antibody staining confirmed CD200S+ cells were CD56+ NK cells. CD200S+ NK cell frequency may be greater in endometriosis patients' endometrium and may affect embryo survival in early pregnancy. In our opinion, regulation of alternative splicing that results in CD200S rather than CD200L may provide new diagnostic and therapeutic options for women with endometriosis.
    Keywords:  CD200; Decidual NK cells; Endometrial NK cells; Endometriosis; Uterine NK cells
    DOI:  https://doi.org/10.1016/j.jri.2022.103477
  2. Nat Commun. 2022 01 18. 13(1): 320
    Maternal-fetal immune responses in pregnant women infected with SARS-CoV-2.
    Valeria Garcia-Flores, Roberto Romero, Yi Xu, Kevin R Theis, Marcia Arenas-Hernandez, Derek Miller, Azam Peyvandipour, Gaurav Bhatti, Jose Galaz, Meyer Gershater, Dustyn Levenson, Errile Pusod, Li Tao, David Kracht, Violetta Florova, Yaozhu Leng, Kenichiro Motomura, Robert Para, Megan Faucett, Chaur-Dong Hsu, Gary Zhang, Adi L Tarca, Roger Pique-Regi, Nardhy Gomez-Lopez.
      Pregnant women represent a high-risk population for severe/critical COVID-19 and mortality. However, the maternal-fetal immune responses initiated by SARS-CoV-2 infection, and whether this virus is detectable in the placenta, are still under investigation. Here we show that SARS-CoV-2 infection during pregnancy primarily induces unique inflammatory responses at the maternal-fetal interface, which are largely governed by maternal T cells and fetal stromal cells. SARS-CoV-2 infection during pregnancy is also associated with humoral and cellular immune responses in the maternal blood, as well as with a mild cytokine response in the neonatal circulation (i.e., umbilical cord blood), without compromising the T-cell repertoire or initiating IgM responses. Importantly, SARS-CoV-2 is not detected in the placental tissues, nor is the sterility of the placenta compromised by maternal viral infection. This study provides insight into the maternal-fetal immune responses triggered by SARS-CoV-2 and emphasizes the rarity of placental infection.
    DOI:  https://doi.org/10.1038/s41467-021-27745-z
  3. Placenta. 2022 Jan 13. pii: S0143-4004(22)00018-2. [Epub ahead of print]118 66-69
    Antiphospholipid antibodies do not cause retargeting of placental extracellular vesicles in the maternal body.
    Bridget W Tsai, Sandy Lau, Song Yee Paek, Michelle Wise, Ian Kando, Peter Stone, Qi Chen, Lawrence W Chamley.
      Antiphospholipid antibodies (aPL) are autoantibodies that cause pregnancy disorders by a poorly defined mechanism that involves the placenta. The human placenta is covered by a single multinucleated cell, the syncytiotrophoblast, which extrudes vast numbers of extracellular vesicles (EVs) into the maternal blood. Extracellular vesicles are tiny packages of cellular material used by cells for remote signalling. In normal pregnancy, placental EVs assist maternal adaptations to pregnancy. We have previously shown that aPL alter the cargo of placental EVs, increasing the load of danger signals. These changes in EV cargo may explain how aPL contribute to the increased risk of recurrent miscarriage, preeclampsia and stillbirths observed in aPL-affected pregnancies. An additional possibility, that aPL alters the targeting of placental EVs to maternal organs to cause maternal maladaptation to pregnancy was investigated in this study.
    Keywords:  Antiphospholipid; Exosome; Extracellular vesicle; Lupus anticoagulant; Microvesicle; Placenta
    DOI:  https://doi.org/10.1016/j.placenta.2022.01.008
  4. Development. 2022 Jan 20. pii: dev.200013. [Epub ahead of print]
    Immune landscape of human placental villi using single-cell analysis.
    Jessica M Toothaker, Oluwabunmi Olaloye, Blake T McCourt, Collin C McCourt, Tatiana N Silva, Rebecca M Case, Peng Liu, Dean Yimlamai, George Tseng, Liza Konnikova.
      Maintenance of healthy pregnancy is reliant on successful balance between the fetal and maternal immune systems. Although maternal mechanisms responsible have been well studied, those used by the fetal immune system remain poorly understood. Using suspension mass cytometry and various imaging modalities, we report a complex immune system within the mid-gestation (17-23 weeks) human placental villi (PV). Consistent with recent reports in other fetal organs, T cells with memory phenotypes, though rare in abundance, were detected within the PV tissue and vasculature. Moreover, we determined T cells isolated from PV samples may be more proliferative than adult T cells at baseline after T cell receptor (TCR) stimulation. Collectively, we identified multiple subtypes of fetal immune cells within the PV and specifically highlight the enhanced proliferative capacity of fetal PV T cells.
    Keywords:  Immune cells; Placenta; Pregnancy; T cells
    DOI:  https://doi.org/10.1242/dev.200013
  5. Science. 2022 Jan 21. 375(6578): 253
    Studies reveal dangers of SARS-CoV-2 infection in pregnancy.
    Meredith Wadman.
      Vaccination helps prevent stillbirths, critical care.
    DOI:  https://doi.org/10.1126/science.ada0233
  6. Clin Obstet Gynecol. 2022 Mar 01. 65(1): 1-3
    Foreword: Uterine Transplantation in Pregnancy.
    Liza Johannesson, Anthony R Gregg.
      
    DOI:  https://doi.org/10.1097/GRF.0000000000000681
  7. J Assist Reprod Genet. 2022 Jan 22.
    The role of endometrial staining for CD138 as a marker of chronic endometritis in predicting live birth.
    N S Herlihy, A M Klimczak, S Titus, C Scott, B M Hanson, J K Kim, E Seli, R T Scott.
      PURPOSE: Chronic endometritis (CE) is diagnosed via endometrial biopsy and staining for plasma cells. A threshold plasma cell count that identifies CE and predicts pregnancy outcomes has not been established, and the prevalence of plasma cells in the general infertile population is unknown. The purpose of this study was to determine the prevalence of plasma cells in the general infertile population and whether a threshold exists which predicts live birth.METHODS: Endometrial samples were obtained prospectively from 80 women undergoing IVF, embedded in paraffin, and stained for plasma cells using mouse mono-clonal antibody for CD138. Slides were reviewed at 20× magnification and 10 random images captured. Three reviewers graded each image for plasma cells. Participants underwent single, euploid, and frozen blastocyst transfer.
    RESULTS: Forty-nine percent of samples had ≥1 plasma cell across 10 HPFs, 11% had ≥5 cells across 10 HPFs, and 4% had ≥10 cells across 10 HPFs. There was no difference in prevalence between those who did and did not achieve live birth. Using thresholds of 1, 5, and 10 plasma cells per 10 HPFs, there were no differences in implantation, clinical pregnancy, clinical pregnancy loss, or live birth rates between patients with and without CE.
    CONCLUSION: Endometrial plasma cells are present in half the general infertile population and do not predict implantation, clinical pregnancy, clinical pregnancy loss, or live birth rates at low levels.
    Keywords:  Endometritis; Fertilization in vitro; Infertility; Plasma cells; Pregnancy
    DOI:  https://doi.org/10.1007/s10815-021-02374-z
  8. Nat Med. 2022 Jan 20.
    A blood test to predict pre‑eclampsia.
    Karen O'Leary.
      
    Keywords:  Biomarkers; Pre-eclampsia; Pregnancy outcome
    DOI:  https://doi.org/10.1038/d41591-022-00027-x
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