Reproductive Immunology and Embryo Acceptance
Pregnancy is a test of the fundamental laws of transplantation immunology - the coexistence of genetically disparate tissues without host immune rejection. Advances over recent decades show that implantation and placental development depend on an active state of maternal immune tolerance, and breakd...
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| Format: | Article |
| Language: | English |
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World Scientific Publishing
2023-12-01
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| Series: | Fertility & Reproduction |
| Online Access: | https://www.worldscientific.com/doi/10.1142/S2661318223740511 |
| _version_ | 1797237076772519936 |
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| author | Sarah Robertson |
| author_facet | Sarah Robertson |
| author_sort | Sarah Robertson |
| collection | DOAJ |
| description | Pregnancy is a test of the fundamental laws of transplantation immunology - the coexistence of genetically disparate tissues without host immune rejection. Advances over recent decades show that implantation and placental development depend on an active state of maternal immune tolerance, and breakdown of tolerance is a key contributor to infertility and recurrent pregnancy loss. Tolerance in pregnancy depends on regulatory T (Treg) cells, which are critical to inhibit effector immunity, constrain inflammation, and support maternal vascular adaptations that allow placental access to maternal nutrient supply. Treg cell defects are implicated in disorders of embryo implantation and placental development, but the origins of Treg cell dysfunction are unknown. In recent studies, we have comprehensively analysed the phenotypes and transcriptional profile of peripheral blood Treg cells in individuals with early pregnancy failure (recurrent miscarriage and recurrent implantation failure). Compared to fertile women, women with early pregnancy failure have fewer total Treg cells and altered Treg cell phenotypes, accompanied by lower Treg:Th1 and Treg:Th17 ratios. RNAseq demonstrates an aberrant Treg cell gene expression profile in early pregnancy failure, with upregulation of pro-inflammatory genes including CSF2, IL4, IL17A, IL21, and IFNG. Our data indicate that Treg cell defects in women with early pregnancy failure can arise due to loss of lineage fidelity associated with impaired FOXP3 regulation. Factors including metabolic function, luteal phase progesterone, and male partner seminal fluid components are all implicated in causing Treg cell deficit. Treg cells may be a useful target for therapeutic interventions to improve uterine receptivity, but this will depend on developing diagnostic tests that are informative. Moreover, safe, and effective interventions to modulate these cells are in their infancy, and personalized approaches matched to specific diagnostic criteria will be needed. |
| first_indexed | 2024-04-24T17:14:00Z |
| format | Article |
| id | doaj.art-8d9336da8fb947b4a3f1523bf1618a66 |
| institution | Directory Open Access Journal |
| issn | 2661-3182 2661-3174 |
| language | English |
| last_indexed | 2024-04-24T17:14:00Z |
| publishDate | 2023-12-01 |
| publisher | World Scientific Publishing |
| record_format | Article |
| series | Fertility & Reproduction |
| spelling | doaj.art-8d9336da8fb947b4a3f1523bf1618a662024-03-28T07:54:17ZengWorld Scientific PublishingFertility & Reproduction2661-31822661-31742023-12-01050423723710.1142/S2661318223740511Reproductive Immunology and Embryo AcceptanceSarah Robertson0Professor, The University of Adelaide, AustraliaPregnancy is a test of the fundamental laws of transplantation immunology - the coexistence of genetically disparate tissues without host immune rejection. Advances over recent decades show that implantation and placental development depend on an active state of maternal immune tolerance, and breakdown of tolerance is a key contributor to infertility and recurrent pregnancy loss. Tolerance in pregnancy depends on regulatory T (Treg) cells, which are critical to inhibit effector immunity, constrain inflammation, and support maternal vascular adaptations that allow placental access to maternal nutrient supply. Treg cell defects are implicated in disorders of embryo implantation and placental development, but the origins of Treg cell dysfunction are unknown. In recent studies, we have comprehensively analysed the phenotypes and transcriptional profile of peripheral blood Treg cells in individuals with early pregnancy failure (recurrent miscarriage and recurrent implantation failure). Compared to fertile women, women with early pregnancy failure have fewer total Treg cells and altered Treg cell phenotypes, accompanied by lower Treg:Th1 and Treg:Th17 ratios. RNAseq demonstrates an aberrant Treg cell gene expression profile in early pregnancy failure, with upregulation of pro-inflammatory genes including CSF2, IL4, IL17A, IL21, and IFNG. Our data indicate that Treg cell defects in women with early pregnancy failure can arise due to loss of lineage fidelity associated with impaired FOXP3 regulation. Factors including metabolic function, luteal phase progesterone, and male partner seminal fluid components are all implicated in causing Treg cell deficit. Treg cells may be a useful target for therapeutic interventions to improve uterine receptivity, but this will depend on developing diagnostic tests that are informative. Moreover, safe, and effective interventions to modulate these cells are in their infancy, and personalized approaches matched to specific diagnostic criteria will be needed.https://www.worldscientific.com/doi/10.1142/S2661318223740511 |
| spellingShingle | Sarah Robertson Reproductive Immunology and Embryo Acceptance Fertility & Reproduction |
| title | Reproductive Immunology and Embryo Acceptance |
| title_full | Reproductive Immunology and Embryo Acceptance |
| title_fullStr | Reproductive Immunology and Embryo Acceptance |
| title_full_unstemmed | Reproductive Immunology and Embryo Acceptance |
| title_short | Reproductive Immunology and Embryo Acceptance |
| title_sort | reproductive immunology and embryo acceptance |
| url | https://www.worldscientific.com/doi/10.1142/S2661318223740511 |
| work_keys_str_mv | AT sarahrobertson reproductiveimmunologyandembryoacceptance |