The 'communicatome' of pregnancy: spotlight on cellular and extravesicular chimerism.
Extracellular Vesicles
Feto-maternal Communication
Microchimerism
Pregnancy
Journal
EMBO molecular medicine
ISSN: 1757-4684
Titre abrégé: EMBO Mol Med
Pays: England
ID NLM: 101487380
Informations de publication
Date de publication:
11 Mar 2024
11 Mar 2024
Historique:
received:
13
12
2023
accepted:
14
02
2024
revised:
12
02
2024
medline:
12
3
2024
pubmed:
12
3
2024
entrez:
12
3
2024
Statut:
aheadofprint
Résumé
Communication via biological mediators between mother and fetus are key to reproductive success and offspring's future health. The repertoire of mediators coding signals between mother and fetus is broad and includes soluble factors, membrane-bound particles and immune as well as non-immune cells. Based on the emergence of technological advancements over the last years, considerable progress has been made toward deciphering the "communicatome" between fetus and mother during pregnancy and even after birth. In this context, pregnancy-associated chimerism has sparked the attention among immunologists, since chimeric cells-although low in number-are maintained in the allogeneic host (mother or fetus) for years after birth. Other non-cellular structures of chimerism, e.g. extracellular vesicles (EVs), are increasingly recognized as modulators of pregnancy outcome and offspring's health. We here discuss the origin, distribution and function of pregnancy-acquired microchimerism and chimeric EVs in mother and offspring. We also highlight the pioneering concept of maternal microchimeric cell-derived EVs in offspring. Such insights expand the understanding of pregnancy-associated health or disease risks in mother and offspring.
Identifiants
pubmed: 38467841
doi: 10.1038/s44321-024-00045-x
pii: 10.1038/s44321-024-00045-x
doi:
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Deutsche Forschungsgemeinschaft (DFG)
ID : Clinical Research Unit 296: AR232/25-2
Organisme : Deutsche Forschungsgemeinschaft (DFG)
ID : Research Unit FOR5068: AR232/29-2
Organisme : Authority for Science, Research and Equality, Hanseatic City of Hamburg, Germany
ID : LFF-FV73
Informations de copyright
© 2024. The Author(s).
Références
Albrecht M, Pagenkemper M, Wiessner C, Spohn M, Lütgehetmann M, Jacobsen H, Gabriel G, Zazara DE, Haertel C, Hecher K et al (2022) Infant immunity against viral infections is advanced by the placenta-dependent vertical transfer of maternal antibodies. Vaccine 40:1563–1571
pubmed: 33431223
doi: 10.1016/j.vaccine.2020.12.049
Amenta PS, Gay S, Vaheri A, Martinez-Hernandez A (1986) The extracellular matrix is an integrated unit: ultrastructural localization of collagen types I, III, IV, V, VI, fibronectin, and laminin in human term placenta. Coll Relat Res 6:125–152
pubmed: 3731745
doi: 10.1016/S0174-173X(86)80021-8
Ariga H, Ohto H, Busch MP, Imamura S, Watson R, Reed W, Lee TH (2001) Kinetics of fetal cellular and cell-free DNA in the maternal circulation during and after pregnancy: implications for noninvasive prenatal diagnosis. Transfusion 41:1524–1530
pubmed: 11778067
doi: 10.1046/j.1537-2995.2001.41121524.x
Arutyunyan A, Roberts K, Troulé K, Wong FCK, Sheridan MA, Kats I, Garcia-Alonso L, Velten B, Hoo R, Ruiz-Morales ER et al (2023) Spatial multiomics map of trophoblast development in early pregnancy. Nature 616:143–151
pubmed: 36991123
pmcid: 10076224
doi: 10.1038/s41586-023-05869-0
Auber M, Svenningsen P (2022) An estimate of extracellular vesicle secretion rates of human blood cells. J Extracell Biol 1:e46
doi: 10.1002/jex2.46
Badiavas EV (2004) The potential of bone marrow cells to orchestrate homeostasis and healing in skin. Blood Cells Mol Dis 32:21–23
pubmed: 14757408
doi: 10.1016/j.bcmd.2003.09.011
Barnes MVC, Pantazi P, Holder B (2023) Circulating extracellular vesicles in healthy and pathological pregnancies: a scoping review of methodology, rigour and results. J Extracell Vesicles 12:e12377
pubmed: 37974377
doi: 10.1002/jev2.12377
Basiri M, Pahlavanneshan S (2021) Evaluation of placental alkaline phosphatase expression as a potential target of solid tumors immunotherapy by using gene and protein expression repositories. Cell J 23:717–721
pubmed: 34939766
pmcid: 8665984
Bianchi DW (1999) Fetal cells in the maternal circulation: feasibility for prenatal diagnosis. Br J Haematol 105:574–583
pubmed: 10354115
doi: 10.1046/j.1365-2141.1999.01383.x
Bianchi DW, Zickwolf GK, Weil GJ, Sylvester S, DeMaria MA (1996) Male fetal progenitor cells persist in maternal blood for as long as 27 years postpartum. Proc Natl Acad Sci USA 93:705–708
pubmed: 8570620
pmcid: 40117
doi: 10.1073/pnas.93.2.705
Billingham RE, Brent L, Medawar PB (1953) Actively acquired tolerance of foreign cells. Nature 172:603–606
pubmed: 13099277
doi: 10.1038/172603a0
Boddy AM, Fortunato A, Wilson Sayres M, Aktipis A (2015) Fetal microchimerism and maternal health: a review and evolutionary analysis of cooperation and conflict beyond the womb. Bioessays 37:1106–1118
pubmed: 26316378
pmcid: 4712643
doi: 10.1002/bies.201500059
Bracamonte-Baran W, Florentin J, Zhou Y, Jankowska-Gan E, Haynes WJ, Zhong W, Brennan TV, Dutta P, Claas FH, van Rood JJ et al (2017) Modification of host dendritic cells by microchimerism-derived extracellular vesicles generates split tolerance. Proc Natl Acad Sci USA 114:1099–1104
pubmed: 28096390
pmcid: 5293109
doi: 10.1073/pnas.1618364114
Brennan K, Martin K, FitzGerald SP, O’Sullivan J, Wu Y, Blanco A, Richardson C, Mc Gee MM (2020) A comparison of methods for the isolation and separation of extracellular vesicles from protein and lipid particles in human serum. Sci Rep 10:1039
pubmed: 31974468
pmcid: 6978318
doi: 10.1038/s41598-020-57497-7
Broestl L, Rubin JB, Dahiya S (2018) Fetal microchimerism in human brain tumors. Brain Pathol 28:484–494
pubmed: 28921714
doi: 10.1111/bpa.12557
Bryan JN (2015) Fetal microchimerism in cancer protection and promotion: current understanding in dogs and the implications for human health. AAPS J 17:506–512
pubmed: 25693490
pmcid: 4406952
doi: 10.1208/s12248-015-9731-y
Buca D, Bologna G, D’Amico A, Cugini S, Musca F, Febbo M, D’Arcangelo D, Buca D, Simeone P, Liberati M et al (2020) Extracellular vesicles in feto-maternal crosstalk and pregnancy disorders. Int J Mol Sci 21:2120
pubmed: 32204473
pmcid: 7139847
doi: 10.3390/ijms21062120
Buzas EI (2023) The roles of extracellular vesicles in the immune system. Nat Rev Immunol 23:236–250
pubmed: 35927511
doi: 10.1038/s41577-022-00763-8
Catalano M, O’Driscoll L (2020) Inhibiting extracellular vesicles formation and release: a review of EV inhibitors. J Extracell Vesicles 9:1703244
pubmed: 32002167
doi: 10.1080/20013078.2019.1703244
Cheung S, Barrett C, Chen Q, Groom K, Chamley L, Lau SY (2022) First trimester placental extracellular vesicles likely contribute to the vasodilation of maternal resistance arteries in normal pregnancy. Placenta 129:84–86
pubmed: 36270043
doi: 10.1016/j.placenta.2022.10.008
Chiu HF, Chen CC, Tsai SS, Ho SC, Yang CY (2012) Parity, age at first birth, and risk of death from brain cancer: a population-based cohort study in Taiwan. BMC Public Health 12:857
pubmed: 23046716
pmcid: 3487843
doi: 10.1186/1471-2458-12-857
Choi DS, Kim DK, Kim YK, Gho YS (2015) Proteomics of extracellular vesicles: exosomes and ectosomes. Mass Spectrom Rev 34:474–490
pubmed: 24421117
doi: 10.1002/mas.21420
Cirello V, Recalcati MP, Muzza M, Rossi S, Perrino M, Vicentini L, Beck-Peccoz P, Finelli P, Fugazzola L (2008) Fetal cell microchimerism in papillary thyroid cancer: a possible role in tumor damage and tissue repair. Cancer Res 68:8482–8488
pubmed: 18922922
doi: 10.1158/0008-5472.CAN-08-0672
Clark K, Zhang S, Barthe S, Kumar P, Pivetti C, Kreutzberg N, Reed C, Wang Y, Paxton Z, Farmer D et al (2019) Placental mesenchymal stem cell-derived extracellular vesicles promote myelin regeneration in an animal model of multiple sclerosis. Cells 8:1497
pubmed: 31771176
pmcid: 6952942
doi: 10.3390/cells8121497
Conforti F, Pala L, Pagan E, Bagnardi V, De Pas T, Queirolo P, Pennacchioli E, Catania C, Cocorocchio E, Ferrucci PF et al (2021) Sex-based dimorphism of anticancer immune response and molecular mechanisms of immune evasion. Clin Cancer Res 27:4311–4324
pubmed: 34016641
pmcid: 7611463
doi: 10.1158/1078-0432.CCR-21-0136
Crewe C, Joffin N, Rutkowski JM, Kim M, Zhang F, Towler DA, Gordillo R, Scherer PE (2018) An endothelial-to-adipocyte extracellular vesicle axis governed by metabolic state. Cell 175:695–708.e613
pubmed: 30293865
pmcid: 6195477
doi: 10.1016/j.cell.2018.09.005
Cronqvist T, Erlandsson L, Tannetta D, Hansson SR (2020) Placental syncytiotrophoblast extracellular vesicles enter primary endothelial cells through clathrin-mediated endocytosis. Placenta 100:133–141
pubmed: 32980046
doi: 10.1016/j.placenta.2020.07.006
Cuddapah Sunku C, Gadi V, de Laval de Lacoste B, Guthrie KA, Nelson JL (2010) Maternal and fetal microchimerism in granulocytes. Chimerism 1:11–14
pmcid: 3035109
doi: 10.4161/chim.1.1.13098
de bellefon LM, Heiman P, Kanaan SB, Azzouz DF, Rak JM, Martin M, Roudier J, Roufosse F, Lambert NC (2010) Cells from a vanished twin as a source of microchimerism 40 years later in a male with a scleroderma-like condition. Chimerism 1:56–60
pubmed: 21327048
pmcid: 3023624
doi: 10.4161/chim.1.2.14294
Debnath K, Las Heras K, Rivera A, Lenzini S, Shin J-W (2023) Extracellular vesicle–matrix interactions. Nat Rev Mater 8:390–402
pubmed: 38463907
doi: 10.1038/s41578-023-00551-3
Dixon CL, Urrabaz-Garza R, Trivedi J, Menon R (2018) 606: placental alkaline phosphatase: Is it placenta-specific? Am J Obstet Gynecol 218:S361–S362
Dubernard G, Aractingi S, Oster M, Rouzier R, Mathieu MC, Uzan S, Khosrotehrani K (2008) Breast cancer stroma frequently recruits fetal derived cells during pregnancy. Breast Cancer Res 10:R14
pubmed: 18271969
pmcid: 2374970
doi: 10.1186/bcr1860
Feng Y, Chen Q, Lau SY, Tsai BW, Groom K, Barrett CJ, Chamley LW (2022) The blocking of integrin-mediated interactions with maternal endothelial cells reversed the endothelial cell dysfunction induced by EVs, derived from preeclamptic placentae. Int J Mol Sci 23:13115
pubmed: 36361901
pmcid: 9657319
doi: 10.3390/ijms232113115
Fu W, Lei C, Liu S, Cui Y, Wang C, Qian K, Li T, Shen Y, Fan X, Lin F et al (2019) CAR exosomes derived from effector CAR-T cells have potent antitumour effects and low toxicity. Nat Commun 10:4355
pubmed: 31554797
pmcid: 6761190
doi: 10.1038/s41467-019-12321-3
Fujimoto K, Nakajima A, Hori S, Tanaka Y, Shirasaki Y, Uemura S, Irie N (2022) Whole-embryonic identification of maternal microchimeric cell types in mouse using single-cell RNA sequencing. Sci Rep 12:18313
pubmed: 36333354
pmcid: 9636240
doi: 10.1038/s41598-022-20781-9
Gebara N, Scheel J, Skovronova R, Grange C, Marozio L, Gupta S, Giorgione V, Caicci F, Benedetto C, Khalil A et al (2022) Single extracellular vesicle analysis in human amniotic fluid shows evidence of phenotype alterations in preeclampsia. J Extracell Vesicles 11:e12217
pubmed: 35582873
pmcid: 9115584
doi: 10.1002/jev2.12217
Giebel B, Kordelas L, Börger V (2017) Clinical potential of mesenchymal stem/stromal cell-derived extracellular vesicles. Stem Cell Investig 4:84
pubmed: 29167805
pmcid: 5676188
doi: 10.21037/sci.2017.09.06
Gilmore GL, Haq B, Shadduck RK, Jasthy SL, Lister J (2008) Fetal-maternal microchimerism in normal parous females and parous female cancer patients. Exp Hematol 36:1073–1077
pubmed: 18508187
doi: 10.1016/j.exphem.2008.03.020
Godakumara K, Ord J, Lättekivi F, Dissanayake K, Viil J, Boggavarapu NR, Faridani OR, Jääger K, Velthut-Meikas A, Jaakma Ü et al (2021) Trophoblast derived extracellular vesicles specifically alter the transcriptome of endometrial cells and may constitute a critical component of embryo-maternal communication. Reprod Biol Endocrinol 19:115
pubmed: 34289864
pmcid: 8293585
doi: 10.1186/s12958-021-00801-5
Gurunathan S, Kang MH, Qasim M, Khan K, Kim JH (2021) Biogenesis, membrane trafficking, functions, and next generation nanotherapeutics medicine of extracellular vesicles. Int J Nanomedicine 16:3357–3383
pubmed: 34040369
pmcid: 8140893
doi: 10.2147/IJN.S310357
Guthrie KA, Dugowson CE, Voigt LF, Koepsell TD, Nelson JL (2010) Does pregnancy provide vaccine-like protection against rheumatoid arthritis? Arthritis Rheum 62:1842–1848
pubmed: 20309863
pmcid: 2910625
doi: 10.1002/art.27459
Hall JM, Lingenfelter P, Adams SL, Lasser D, Hansen JA, Bean MA (1995) Detection of maternal cells in human umbilical cord blood using fluorescence in situ hybridization. Blood 86:2829–2832
pubmed: 7545474
doi: 10.1182/blood.V86.7.2829.2829
Han C, Wang C, Chen Y, Wang J, Xu X, Hilton T, Cai W, Zhao Z, Wu Y, Li K et al (2020) Placenta-derived extracellular vesicles induce preeclampsia in mouse models. Haematologica 105:1686–1694
pubmed: 31439676
pmcid: 7271597
doi: 10.3324/haematol.2019.226209
Harpavat S, Finegold MJ, Karpen SJ (2011) Patients with biliary atresia have elevated direct/conjugated bilirubin levels shortly after birth. Pediatrics 128:e1428–e1433
pubmed: 22106076
pmcid: 3387898
doi: 10.1542/peds.2011-1869
Harrington WE, Kanaan SB, Muehlenbachs A, Morrison R, Stevenson P, Fried M, Duffy PE, Nelson JL (2017) Maternal microchimerism predicts increased infection but decreased disease due to Plasmodium falciparum during early childhood. J Infect Dis 215:1445–1451
pubmed: 28329160
pmcid: 5790147
doi: 10.1093/infdis/jix129
Haupt S, Caramia F, Klein SL, Rubin JB, Haupt Y (2021) Sex disparities matter in cancer development and therapy. Nat Rev Cancer 21:393–407
pubmed: 33879867
pmcid: 8284191
doi: 10.1038/s41568-021-00348-y
Hay FC, Hull MG, Torrigiani G (1971) The transfer of human IgG subclasses from mother to foetus. Clin Exp Immunol 9:355–358
pubmed: 4998969
pmcid: 1713070
Hedlund M, Stenqvist AC, Nagaeva O, Kjellberg L, Wulff M, Baranov V, Mincheva-Nilsson L (2009) Human placenta expresses and secretes NKG2D ligands via exosomes that down-modulate the cognate receptor expression: evidence for immunosuppressive function. J Immunol 183:340–351
pubmed: 19542445
doi: 10.4049/jimmunol.0803477
Heidarzadeh M, Zarebkohan A, Rahbarghazi R, Sokullu E (2023) Protein corona and exosomes: new challenges and prospects. Cell Commun Signal 21:64
pubmed: 36973780
pmcid: 10041507
doi: 10.1186/s12964-023-01089-1
Hemberger M, Hanna CW, Dean W (2020) Mechanisms of early placental development in mouse and humans. Nat Rev Genet 21:27–43
pubmed: 31534202
doi: 10.1038/s41576-019-0169-4
Holder BS, Tower CL, Forbes K, Mulla MJ, Aplin JD, Abrahams VM (2012) Immune cell activation by trophoblast-derived microvesicles is mediated by syncytin 1. Immunology 136:184–191
pubmed: 22348442
pmcid: 3403269
doi: 10.1111/j.1365-2567.2012.03568.x
Hoshino A, Costa-Silva B, Shen TL, Rodrigues G, Hashimoto A, Tesic Mark M, Molina H, Kohsaka S, Di Giannatale A, Ceder S et al (2015) Tumour exosome integrins determine organotropic metastasis. Nature 527:329–335
pubmed: 26524530
pmcid: 4788391
doi: 10.1038/nature15756
Huppertz B, Kaufmann P, Kingdom J (2002) Trophoblast turnover in health and disease. Fetal Maternal Med Rev 13:103–118
doi: 10.1017/S0965539502000220
Iannotta D, Amruta A, Kijas AW, Rowan AE, Wolfram J (2024) Entry and exit of extracellular vesicles to and from the blood circulation. Nat Nanotechnol 19:13–20
pubmed: 38110531
doi: 10.1038/s41565-023-01522-z
James-Allan LB, Rosario FJ, Barner K, Lai A, Guanzon D, McIntyre HD, Lappas M, Powell TL, Salomon C, Jansson T (2020) Regulation of glucose homeostasis by small extracellular vesicles in normal pregnancy and in gestational diabetes. FASEB J 34:5724–5739
pubmed: 32154621
doi: 10.1096/fj.201902522RR
Johnson KL, Samura O, Nelson JL, McDonnell MDWM, Bianchi DW (2002) Significant fetal cell microchimerism in a nontransfused woman with hepatitis C: evidence of long-term survival and expansion. Hepatology 36:1295–1297
pubmed: 12395344
doi: 10.1053/jhep.2002.35622
Jonsson AM, Uzunel M, Götherström C, Papadogiannakis N, Westgren M (2008) Maternal microchimerism in human fetal tissues. Am J Obstet Gynecol 198:325.e321–326
doi: 10.1016/j.ajog.2007.09.047
Kaisanlahti A, Turunen J, Byts N, Samoylenko A, Bart G, Virtanen N, Tejesvi MV, Zhyvolozhnyi A, Sarfraz S, Kumpula S et al (2023) Maternal microbiota communicates with the fetus through microbiota-derived extracellular vesicles. Microbiome 11:249
pubmed: 37953319
pmcid: 10642029
doi: 10.1186/s40168-023-01694-9
Kamper-Jørgensen M, Biggar RJ, Tjønneland A, Hjalgrim H, Kroman N, Rostgaard K, Stamper CL, Olsen A, Andersen AM, Gadi VK (2012) Opposite effects of microchimerism on breast and colon cancer. Eur J Cancer 48:2227–2235
pubmed: 22397765
doi: 10.1016/j.ejca.2012.02.006
Kang M, Blenkiron C, Chamley LW (2023) The biodistribution of placental and fetal extracellular vesicles during pregnancy following placentation. Clin Sci 137:385–399
doi: 10.1042/CS20220301
Kara RJ, Bolli P, Karakikes I, Matsunaga I, Tripodi J, Tanweer O, Altman P, Shachter NS, Nakano A, Najfeld V et al (2012) Fetal cells traffic to injured maternal myocardium and undergo cardiac differentiation. Circ Res 110:82–93
pubmed: 22082491
doi: 10.1161/CIRCRESAHA.111.249037
Kinder JM, Jiang TT, Ertelt JM, Xin L, Strong BS, Shaaban AF, Way SS (2015) Cross-generational reproductive fitness enforced by microchimeric maternal cells. Cell 162:505–515
pubmed: 26213383
pmcid: 4522363
doi: 10.1016/j.cell.2015.07.006
Kinder JM, Stelzer IA, Arck PC, Way SS (2017) Immunological implications of pregnancy-induced microchimerism. Nat Rev Immunol 17:483–494
pubmed: 28480895
pmcid: 5532073
doi: 10.1038/nri.2017.38
Knight M, Redman CW, Linton EA, Sargent IL (1998) Shedding of syncytiotrophoblast microvilli into the maternal circulation in pre-eclamptic pregnancies. Br J Obstet Gynaecol 105:632–640
pubmed: 9647154
doi: 10.1111/j.1471-0528.1998.tb10178.x
Kovács ÁF, Fekete N, Turiák L, Ács A, Kőhidai L, Buzás EI, Pállinger É (2019) Unravelling the role of trophoblastic-derived extracellular vesicles in regulatory T cell differentiation. Int J Mol Sci 20:3457
pubmed: 31337116
pmcid: 6678568
doi: 10.3390/ijms20143457
Kshirsagar SK, Alam SM, Jasti S, Hodes H, Nauser T, Gilliam M, Billstrand C, Hunt JS, Petroff MG (2012) Immunomodulatory molecules are released from the first trimester and term placenta via exosomes. Placenta 33:982–990
pubmed: 23107341
pmcid: 3534832
doi: 10.1016/j.placenta.2012.10.005
Kulaj K, Harger A, Bauer M, Caliskan ÖS, Gupta TK, Chiang DM, Milbank E, Reber J, Karlas A, Kotzbeck P et al (2023) Adipocyte-derived extracellular vesicles increase insulin secretion through transport of insulinotropic protein cargo. Nat Commun 14:709
pubmed: 36759608
pmcid: 9911726
doi: 10.1038/s41467-023-36148-1
Kupper N, Huppertz B (2022) The endogenous exposome of the pregnant mother: placental extracellular vesicles and their effect on the maternal system. Mol Aspects Med 87:100955
pubmed: 33612320
doi: 10.1016/j.mam.2021.100955
Lambert N, Lee Nelson J (2003) Microchimerism in autoimmune disease: more questions than answers? Autoimmun Rev 2:133–139
pubmed: 12848954
doi: 10.1016/S1568-9972(02)00149-0
Lee GM, Johnstone B, Jacobson K, Caterson B (1993) The dynamic structure of the pericellular matrix on living cells. J Cell Biol 123:1899–1907
pubmed: 8276905
doi: 10.1083/jcb.123.6.1899
Leitner K, Szlauer R, Ellinger I, Ellinger A, Zimmer KP, Fuchs R (2001) Placental alkaline phosphatase expression at the apical and basal plasma membrane in term villous trophoblasts. J Histochem Cytochem 49:1155–1164
pubmed: 11511684
doi: 10.1177/002215540104900909
Leveque L, Hodgson S, Peyton S, Koyama M, MacDonald KP, Khosrotehrani K (2014) Selective organ specific inflammation in offspring harbouring microchimerism from strongly alloreactive mothers. J Autoimmun 50:51–58
pubmed: 24268809
doi: 10.1016/j.jaut.2013.10.005
Li H, Pinilla-Macua I, Ouyang Y, Sadovsky E, Kajiwara K, Sorkin A, Sadovsky Y (2020) Internalization of trophoblastic small extracellular vesicles and detection of their miRNA cargo in P-bodies. J Extracell Vesicles 9:1812261
pubmed: 32944196
pmcid: 7480505
doi: 10.1080/20013078.2020.1812261
Li Y-H, Zhang D, Du M-R (2021) Advances and challenges of mesenchymal stem cells for pregnancy-related diseases. Cell Mol Immunol 18:2075–2077
pubmed: 34172931
pmcid: 8322408
doi: 10.1038/s41423-021-00707-7
Li Z, Tao M, Huang M, Pan W, Huang Q, Wang P, Zhang Y, Situ B, Zheng L (2023) Quantification of placental extracellular vesicles in different pregnancy status via single particle analysis method. Clin Chim Acta 539:266–273
pubmed: 36587781
doi: 10.1016/j.cca.2022.12.021
Lindtke D, Seefried FR, Drögemüller C, Neuditschko M (2023) Increased heterozygosity in low-pass sequencing data allows identification of blood chimeras in cattle. Anim Genet 54:613–618
pubmed: 37313694
doi: 10.1111/age.13334
Lishner M (2003) Cancer in pregnancy. Annal Oncol 14:iii31–iii36
doi: 10.1093/annonc/mdg745
Lo YM, Tein MS, Lau TK, Haines CJ, Leung TN, Poon PM, Wainscoat JS, Johnson PJ, Chang AM, Hjelm NM (1998) Quantitative analysis of fetal DNA in maternal plasma and serum: implications for noninvasive prenatal diagnosis. Am J Hum Genet 62:768–775
pubmed: 9529358
pmcid: 1377040
doi: 10.1086/301800
Loubière LS, Lambert NC, Flinn LJ, Erickson TD, Yan Z, Guthrie KA, Vickers KT, Nelson JL (2006) Maternal microchimerism in healthy adults in lymphocytes, monocyte/macrophages and NK cells. Lab Investig 86:1185–1192
pubmed: 16969370
doi: 10.1038/labinvest.3700471
Lundberg V, Berglund M, Skogberg G, Lindgren S, Lundqvist C, Gudmundsdottir J, Thörn K, Telemo E, Ekwall O (2016) Thymic exosomes promote the final maturation of thymocytes. Sci Rep 6:36479
pubmed: 27824109
pmcid: 5099897
doi: 10.1038/srep36479
Luo S-S, Ishibashi O, Ishikawa G, Ishikawa T, Katayama A, Mishima T, Takizawa T, Shigihara T, Goto T, Izumi A et al (2009) Human villous trophoblasts express and secrete placenta-specific microRNAs into maternal circulation via exosomes1. Biol Reprod 81:717–729
pubmed: 19494253
doi: 10.1095/biolreprod.108.075481
Lustgraaf EC, Fuson RB, Eichwald EJ (1960) Sex tolerance and split tolerance. Plast Reconstr Surg 26:145–150
pubmed: 14419035
doi: 10.1097/00006534-196007000-00050
Madani G, Heiner DC (1989) Antibody transmission from mother to fetus. Curr Opin Immunol 1:1157–1164
pubmed: 2679753
doi: 10.1016/0952-7915(89)90009-5
Maloney S, Smith A, Furst DE, Myerson D, Rupert K, Evans PC, Nelson JL (1999) Microchimerism of maternal origin persists into adult life. J Clin Investig 104:41–47
pubmed: 10393697
pmcid: 408407
doi: 10.1172/JCI6611
Mathe G, Amiel JL, Schwarzenberg L, Cattan A, Schneider M (1963) Haematopoietic chimera in man after allogenic (homologous) bone-marrow transplantation. (Control of the secondary syndrome. specific tolerance due to the chimerism). Br Med J 2:1633–1635
pubmed: 14066188
pmcid: 1873894
doi: 10.1136/bmj.2.5373.1633
Mathieu M, Martin-Jaular L, Lavieu G, Théry C (2019) Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication. Nat Cell Biol 21:9–17
pubmed: 30602770
doi: 10.1038/s41556-018-0250-9
Menon R, Debnath C, Lai A, Guanzon D, Bhatnagar S, Kshetrapal P, Sheller-Miller S, Salomon C (2020) Protein Profile changes in circulating placental extracellular vesicles in term and preterm births: a longitudinal study. Endocrinology 161:bqaa009
pubmed: 31995166
pmcid: 7102872
doi: 10.1210/endocr/bqaa009
Mold JE, Michaëlsson J, Burt TD, Muench MO, Beckerman KP, Busch MP, Lee TH, Nixon DF, McCune JM (2008) Maternal alloantigens promote the development of tolerogenic fetal regulatory T cells in utero. Science 322:1562–1565
pubmed: 19056990
pmcid: 2648820
doi: 10.1126/science.1164511
Morales-Prieto DM, Favaro RR, Markert UR (2020) Placental miRNAs in feto-maternal communication mediated by extracellular vesicles. Placenta 102:27–33
pubmed: 33218575
doi: 10.1016/j.placenta.2020.07.001
Motta-Mejia C, Kandzija N, Zhang W, Mhlomi V, Cerdeira AS, Burdujan A, Tannetta D, Dragovic R, Sargent IL, Redman CW et al (2017) Placental vesicles carry active endothelial nitric oxide synthase and their activity is reduced in preeclampsia. Hypertension 70:372–381
pubmed: 28607124
doi: 10.1161/HYPERTENSIONAHA.117.09321
Muraji T, Masuya R, Harumatsu T, Kawano T, Muto M, Ieiri S (2022) New insights in understanding biliary atresia from the perspectives on maternal microchimerism. Front Pediatr 10:1007987
pubmed: 36210938
pmcid: 9539747
doi: 10.3389/fped.2022.1007987
Nair S, Guanzon D, Jayabalan N, Lai A, Scholz-Romero K, Kalita de Croft P, Ormazabal V, Palma C, Diaz E, McCarthy EA et al (2021) Extracellular vesicle-associated miRNAs are an adaptive response to gestational diabetes mellitus. J Transl Med 19:360
pubmed: 34416903
pmcid: 8377872
doi: 10.1186/s12967-021-02999-9
Nassar D, Droitcourt C, Mathieu-d’Argent E, Kim MJ, Khosrotehrani K, Aractingi S (2012) Fetal progenitor cells naturally transferred through pregnancy participate in inflammation and angiogenesis during wound healing. FASEB J 26:149–157
pubmed: 21974929
doi: 10.1096/fj.11-180695
Nelson JL (2012) The otherness of self: microchimerism in health and disease. Trends Immunol 33:421–427
pubmed: 22609148
pmcid: 3516290
doi: 10.1016/j.it.2012.03.002
Nelson JL, Gillespie KM, Lambert NC, Stevens AM, Loubiere LS, Rutledge JC, Leisenring WM, Erickson TD, Yan Z, Mullarkey ME et al (2007) Maternal microchimerism in peripheral blood in type 1 diabetes and pancreatic islet beta cell microchimerism. Proc Natl Acad Sci USA 104:1637–1642
pubmed: 17244711
pmcid: 1785262
doi: 10.1073/pnas.0606169104
Nguyen SL, Ahn SH, Greenberg JW, Collaer BW, Agnew DW, Arora R, Petroff MG (2021) Integrins mediate placental extracellular vesicle trafficking to lung and liver in vivo. Sci Rep 11:4217
pubmed: 33602965
pmcid: 7893009
doi: 10.1038/s41598-021-82752-w
Nguyen Huu S, Oster M, Avril M-F, Boitier F, Mortier L, Richard M-A, Kerob D, Maubec E, Souteyrand P, Moguelet P et al (2009a) Fetal microchimeric cells participate in tumour angiogenesis in melanomas occurring during pregnancy. Am J Pathol 174:630–637
pubmed: 19147820
pmcid: 2630570
doi: 10.2353/ajpath.2009.080566
Nguyen Huu S, Oster M, Avril MF, Boitier F, Mortier L, Richard MA, Kerob D, Maubec E, Souteyrand P, Moguelet P et al (2009b) Fetal microchimeric cells participate in tumour angiogenesis in melanomas occurring during pregnancy. Am J Pathol 174:630–637
pubmed: 19147820
pmcid: 2630570
doi: 10.2353/ajpath.2009.080566
Noone AMHN, Krapcho M, Miller D, Brest A, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (2018) SEER cancer statistics review, 1975-2012. National Cancer Institute, Bethesda, MD. https://seer.cancer.gov/csr/1975_2015/ , based on November 2017 SEER data submission, posted to the SEER web site, April 2018.
O’Donoghue K (2008) Fetal microchimerism and maternal health during and after pregnancy. Obstet Med 1:56–64
pubmed: 27582787
pmcid: 4989712
doi: 10.1258/om.2008.080008
Osada H, Doi S, Fukushima T, Nakauchi H, Seki K, Sekiya S (2001) Detection of fetal HPCs in maternal circulation after delivery. Transfusion 41:499–503
pubmed: 11316901
doi: 10.1046/j.1537-2995.2001.41040499.x
Ouyang Y, Bayer A, Chu T, Tyurin VA, Kagan VE, Morelli AE, Coyne CB, Sadovsky Y (2016) Isolation of human trophoblastic extracellular vesicles and characterization of their cargo and antiviral activity. Placenta 47:86–95
pubmed: 27780544
pmcid: 5123854
doi: 10.1016/j.placenta.2016.09.008
Owen RD (1945) Immunogenetic consequences of vascular anastomoses between bovine twins. Science 102:400–401
pubmed: 17755278
doi: 10.1126/science.102.2651.400
Page EW (1957) Transfer of materials across the human placenta. Am J Obstet Gynecol 74:705–715. discussion 715-708
pubmed: 13458277
doi: 10.1016/0002-9378(57)90050-9
Pap E, Pállinger E, Falus A, Kiss AA, Kittel A, Kovács P, Buzás EI (2008) T lymphocytes are targets for platelet- and trophoblast-derived microvesicles during pregnancy. Placenta 29:826–832
pubmed: 18684502
doi: 10.1016/j.placenta.2008.06.006
Ponsonby AL, Lucas RM, van der Mei IA, Dear K, Valery PC, Pender MP, Taylor BV, Kilpatrick TJ, Coulthard A, Chapman C et al (2012) Offspring number, pregnancy, and risk of a first clinical demyelinating event: the AusImmune Study. Neurology 78:867–874
pubmed: 22402857
doi: 10.1212/WNL.0b013e31824c4648
Raposo G, Nijman HW, Stoorvogel W, Liejendekker R, Harding CV, Melief CJ, Geuze HJ (1996) B lymphocytes secrete antigen-presenting vesicles. J Exp Med 183:1161–1172
pubmed: 8642258
doi: 10.1084/jem.183.3.1161
Rebmann V, König L, Nardi Fda S, Wagner B, Manvailer LF, Horn PA (2016) The potential of HLA-G-bearing extracellular vesicles as a future element in HLA-G immune biology. Front Immunol 7:173
pubmed: 27199995
pmcid: 4854879
doi: 10.3389/fimmu.2016.00173
Redman CW, Sargent IL (2000) Placental debris, oxidative stress and pre-eclampsia. Placenta 21:597–602
pubmed: 10985960
doi: 10.1053/plac.2000.0560
Sabapatha A, Gercel-Taylor C, Taylor DD (2006) Specific isolation of placenta-derived exosomes from the circulation of pregnant women and their immunoregulatory consequences. Am J Reprod Immunol 56:345–355
pubmed: 17076679
doi: 10.1111/j.1600-0897.2006.00435.x
Salomon C, Kobayashi M, Ashman K, Sobrevia L, Mitchell MD, Rice GE (2013) Hypoxia-induced changes in the bioactivity of cytotrophoblast-derived exosomes. PLoS ONE 8:e79636
pubmed: 24244532
pmcid: 3823597
doi: 10.1371/journal.pone.0079636
Salomon C, Scholz-Romero K, Sarker S, Sweeney E, Kobayashi M, Correa P, Longo S, Duncombe G, Mitchell MD, Rice GE et al (2016) Gestational diabetes mellitus is associated with changes in the concentration and bioactivity of placenta-derived exosomes in maternal circulation across gestation. Diabetes 65:598–609
pubmed: 26718504
doi: 10.2337/db15-0966
Salomon C, Torres MJ, Kobayashi M, Scholz-Romero K, Sobrevia L, Dobierzewska A, Illanes SE, Mitchell MD, Rice GE (2014) A gestational profile of placental exosomes in maternal plasma and their effects on endothelial cell migration. PLoS ONE 9:e98667
pubmed: 24905832
pmcid: 4048215
doi: 10.1371/journal.pone.0098667
Sarker S, Scholz-Romero K, Perez A, Illanes SE, Mitchell MD, Rice GE, Salomon C (2014) Placenta-derived exosomes continuously increase in maternal circulation over the first trimester of pregnancy. J Transl Med 12:204
pubmed: 25104112
pmcid: 4283151
doi: 10.1186/1479-5876-12-204
Schepanski S, Chini M, Sternemann V, Urbschat C, Thiele K, Sun T, Zhao Y, Poburski M, Woestemeier A, Thieme MT et al (2022) Pregnancy-induced maternal microchimerism shapes neurodevelopment and behavior in mice. Nat Commun 13:4571
pubmed: 35931682
pmcid: 9356013
doi: 10.1038/s41467-022-32230-2
Schmorl C (1893) Pathologisch-anatomische Untersuchungen uber Puerperal-Eklampsie. Verlag FCW Vogel
Sedov E, McCarthy J, Koren E, Fuchs Y (2022) Fetomaternal microchimerism in tissue repair and tumor development. Dev Cell 57:1442–1452
pubmed: 35700729
doi: 10.1016/j.devcel.2022.05.018
Shao TY, Kinder JM, Harper G, Pham G, Peng Y, Liu J, Gregory EJ, Sherman BE, Wu Y, Iten AE et al (2023) Reproductive outcomes after pregnancy-induced displacement of preexisting microchimeric cells. Science 381:1324–1330
pubmed: 37733857
doi: 10.1126/science.adf9325
Sheller-Miller S, Choi K, Choi C, Menon R (2019) Cyclic-recombinase-reporter mouse model to determine exosome communication and function during pregnancy. Am J Obstet Gynecol 221:502.e501–502.e512
doi: 10.1016/j.ajog.2019.06.010
Sheller-Miller S, Lei J, Saade G, Salomon C, Burd I, Menon R (2016) Feto-maternal trafficking of exosomes in murine pregnancy models. Front Pharmacol 7:432
pubmed: 27895585
pmcid: 5108780
doi: 10.3389/fphar.2016.00432
Skogberg G, Lundberg V, Berglund M, Gudmundsdottir J, Telemo E, Lindgren S, Ekwall O (2015) Human thymic epithelial primary cells produce exosomes carrying tissue-restricted antigens. Immunol Cell Biol 93:727–734
pubmed: 25776846
pmcid: 4575951
doi: 10.1038/icb.2015.33
Smith NC, Brush MG, Luckett S (1974) Preparation of human placental villous surface membrane. Nature 252:302–303
pubmed: 4431448
doi: 10.1038/252302b0
Soncin F, Khater M, To C, Pizzo D, Farah O, Wakeland A, Arul Nambi Rajan K, Nelson KK, Chang CW, Moretto-Zita M et al (2018) Comparative analysis of mouse and human placentae across gestation reveals species-specific regulators of placental development. Development 145:dev156273
pubmed: 29361559
pmcid: 5825847
doi: 10.1242/dev.156273
Song P, Anna B, E Scott G, Chamley LW (2023) The interaction of placental micro-EVs with immune cells in vivo and in vitro. Am J Reprod Immunol 90:e13766
pubmed: 37641368
doi: 10.1111/aji.13766
Spaans F, Quon A, Kirschenman R, Morton JS, Sawamura T, Tannetta DS, Sargent IL, Davidge ST (2020) Role of lectin-like oxidized LDL receptor-1 and syncytiotrophoblast extracellular vesicles in the vascular reactivity of mouse uterine arteries during pregnancy. Sci Rep 10:6046
pubmed: 32269313
pmcid: 7142154
doi: 10.1038/s41598-020-63205-2
Sprent J, Hurd M, Schaefer M, Heath W (1995) Split tolerance in spleen chimeras. J Immunol 154:1198–1206
pubmed: 7822792
doi: 10.4049/jimmunol.154.3.1198
Stelzer IA, Urbschat C, Schepanski S, Thiele K, Triviai I, Wieczorek A, Alawi M, Ohnezeit D, Kottlau J, Huang J et al (2021) Vertically transferred maternal immune cells promote neonatal immunity against early life infections. Nat Commun 12:4706
pubmed: 34349112
pmcid: 8338998
doi: 10.1038/s41467-021-24719-z
Stenqvist A-C, Nagaeva O, Baranov V, Mincheva-Nilsson L (2013) Exosomes secreted by human placenta carry functional Fas ligand and TRAIL molecules and convey apoptosis in activated immune cells, suggesting exosome-mediated immune privilege of the fetus. J Immunol 191:5515–5523
pubmed: 24184557
doi: 10.4049/jimmunol.1301885
Stevens AM, Hermes HM, Rutledge JC, Buyon JP, Nelson JL (2003) Myocardial-tissue-specific phenotype of maternal microchimerism in neonatal lupus congenital heart block. Lancet 362:1617–1623
pubmed: 14630442
doi: 10.1016/S0140-6736(03)14795-2
Straub RH (2007) The complex role of estrogens in inflammation. Endocr Rev 28:521–574
pubmed: 17640948
doi: 10.1210/er.2007-0001
Taylor SK, Houshdaran S, Robinson JF, Gormley MJ, Kwan EY, Kapidzic M, Schilling B, Giudice LC, Fisher SJ (2020) Cytotrophoblast extracellular vesicles enhance decidual cell secretion of immune modulators via TNFα. Development 147:dev187013
pubmed: 32747437
pmcid: 7502596
doi: 10.1242/dev.187013
Tedford E, Badya NB, Laing C, Asaoka N, Kaneko S, Filippi BM, McConkey GA (2023) Infection-induced extracellular vesicles evoke neuronal transcriptional and epigenetic changes. Sci Rep 13:6913
pubmed: 37106020
pmcid: 10140046
doi: 10.1038/s41598-023-34074-2
Tersigni C, Furqan Bari M, Cai S, Zhang W, Kandzija N, Buchan A, Miranda F, Di Simone N, Redman CW, Bastie C et al (2022) Syncytiotrophoblast-derived extracellular vesicles carry apolipoprotein-E and affect lipid synthesis of liver cells in vitro. J Cell Mol Med 26:123–132
pubmed: 34894055
doi: 10.1111/jcmm.17056
Théry C, Witwer KW, Aikawa E, Alcaraz MJ, Anderson JD, Andriantsitohaina R, Antoniou A, Arab T, Archer F, Atkin-Smith GK et al (2018) Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J Extracell Vesicles 7:1535750
pubmed: 30637094
pmcid: 6322352
doi: 10.1080/20013078.2018.1535750
Thiele K, Ahrendt LS, Hecher K, Arck PC (2019) The mnemonic code of pregnancy: comparative analyses of pregnancy success and complication risk in first and second human pregnancies. J Reprod Immunol 134-135:11–20
pubmed: 31374263
doi: 10.1016/j.jri.2019.06.003
Thomas MR, Williamson R, Craft I, Yazdani N, Rodeck CH (1994) Y chromosome sequence DNA amplified from peripheral blood of women in early pregnancy. Lancet 343:413–414
pubmed: 7905562
doi: 10.1016/S0140-6736(94)91248-3
Tiozzo C, Bustoros M, Lin X, Manzano De Mejia C, Gurzenda E, Chavez M, Hanna I, Aguiari P, Perin L, Hanna N (2021) Placental extracellular vesicles-associated microRNA-519c mediates endotoxin adaptation in pregnancy. Am J Obstet Gynecol 225:681.e681–681.e620
doi: 10.1016/j.ajog.2021.06.075
Tong M, Abrahams VM, Chamley LW (2018) Immunological effects of placental extracellular vesicles. Immunol Cell Biol https://doi.org/10.1111/imcb.12049
Tong M, Chamley LW (2018) Isolation and characterization of extracellular vesicles from ex vivo cultured human placental explants. Methods Mol Biol 1710:117–129
pubmed: 29196998
doi: 10.1007/978-1-4939-7498-6_9
Tong M, Chen Q, James JL, Wise MR, Stone PR, Chamley LW (2017a) In vivo targets of human placental micro-vesicles vary with exposure time and pregnancy. Reproduction 153:835–845
pubmed: 28356498
doi: 10.1530/REP-16-0615
Tong M, Kleffmann T, Pradhan S, Johansson CL, DeSousa J, Stone PR, James JL, Chen Q, Chamley LW (2016) Proteomic characterization of macro-, micro- and nano-extracellular vesicles derived from the same first trimester placenta: relevance for feto-maternal communication. Hum Reprod 31:687–699
pubmed: 26839151
doi: 10.1093/humrep/dew004
Tong M, Stanley JL, Chen Q, James JL, Stone PR, Chamley LW (2017b) Placental nano-vesicles target to specific organs and modulate vascular tone in vivo. Hum Reprod 32:2188–2198
pubmed: 29040541
doi: 10.1093/humrep/dex310
Tóth E, Turiák L, Visnovitz T, Cserép C, Mázló A, Sódar BW, Försönits AI, Petővári G, Sebestyén A, Komlósi Z et al (2021) Formation of a protein corona on the surface of extracellular vesicles in blood plasma. J Extracell Vesicles 10:e12140
pubmed: 34520123
pmcid: 8439280
doi: 10.1002/jev2.12140
Tricarico C, Clancy J, D’Souza-Schorey C (2017) Biology and biogenesis of shed microvesicles. Small GTPases 8:220–232
pubmed: 27494381
doi: 10.1080/21541248.2016.1215283
Tsai BW, Lau S, Paek SY, Wise M, Kando I, Stone P, Chen Q, Chamley LW (2022) Antiphospholipid antibodies do not cause retargeting of placental extracellular vesicles in the maternal body. Placenta 118:66–69
pubmed: 35042085
doi: 10.1016/j.placenta.2022.01.008
Tyagi AM, Srivastava K, Mansoori MN, Trivedi R, Chattopadhyay N, Singh D (2012) Estrogen deficiency induces the differentiation of IL-17 secreting Th17 cells: a new candidate in the pathogenesis of osteoporosis. PLoS ONE 7:e44552
pubmed: 22970248
pmcid: 3438183
doi: 10.1371/journal.pone.0044552
Vanzyl B, Planas R, Ye Y, Foulis A, de Krijger RR, Vives-Pi M, Gillespie KM (2010) Why are levels of maternal microchimerism higher in type 1 diabetes pancreas? Chimerism 1:45–50
pubmed: 21327046
pmcid: 3023622
doi: 10.4161/chim.1.2.13891
Wong JH, Sterns EE, Kopald KH, Nizze JA, Morton DL (1989) Prognostic significance of pregnancy in stage I melanoma. Archiv Surg 124:1227–1231
doi: 10.1001/archsurg.1989.01410100133023
Wong VA, Dinh KN, Chen G, Wrenshall LE (2023) IL-2RαKO mice exhibit maternal microchimerism and reveal nuclear localization of IL-2Rα in lymphoid and non-lymphoid cells. Preprint at bioRxiv https://www.biorxiv.org/content/10.1101/2023.11.03.565571v2.full.pdf
Yüzen D, Urbschat C, Schepanski S, Thiele K, Arck PC, Mittrücker HW (2023) Pregnancy-induced transfer of pathogen-specific T cells from mother to fetus in mice. EMBO Rep 24:e56829
pubmed: 37610043
pmcid: 10561172
doi: 10.15252/embr.202356829
Zhang Y, Tang Y, Liu Y, Wang J, Shen Y, Sun X, Kang M, Zhao M, Chen Q (2022) The autocrine role of placental extracellular vesicles from missed miscarriage in causing senescence: possible pathogenesis of missed miscarriage. Cells 11:3873
pubmed: 36497129
pmcid: 9740889
doi: 10.3390/cells11233873
Zierden HC, Marx-Rattner R, Rock KD, Montgomery KR, Anastasiadis P, Folts L, Bale TL (2023) Extracellular vesicles are dynamic regulators of maternal glucose homeostasis during pregnancy. Sci Rep 13:4568
pubmed: 36941297
pmcid: 10027885
doi: 10.1038/s41598-023-31425-x