Regulatory T cells are paramount effectors in progesterone regulation of embryo implantation and fetal growth
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Date
2023
Authors
Green, E.S.
Moldenhauer, L.M.
Groome, H.M.
Sharkey, D.J.
Chin, P.Y.
Care, A.S.
Robker, R.L.
McColl, S.R.
Robertson, S.A.
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Journal article
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JCI Insight, 2023; 8(11):1-19
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Ella S. Green, Lachlan M. Moldenhauer, Holly M. Groome, David J. Sharkey, Peck Y. Chin, Alison S. Care, Rebecca L. Robker, Shaun R. McColl, and Sarah A., Robertson
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Abstract
Progesterone (P4) is essential for embryo implantation, but the extent to which the pro-gestational effects of P4 depend on the maternal immune compartment is unknown. Here, we investigate whether regulatory T cells (Treg cells) act to mediate luteal phase P4 effects on uterine receptivity in mice. P4 antagonist RU486 administered to mice on days 0.5 and 2.5 post coitum (dpc) to model luteal phase P4 deficiency caused fewer CD4+Foxp3+ Treg cells and impaired Treg functional competence, along with dysfunctional uterine vascular remodeling and perturbed placental development in mid-gestation. These effects were linked with fetal loss and fetal growth restriction, accompanied by a Th1/CD8-skewed T cell profile. Adoptive transfer at implantation of Treg cells - but not T conventional (Tconv) cells - alleviated fetal loss and fetal growth restriction by mitigating adverse effects of reduced P4 signaling on uterine blood vessel remodeling and placental structure, and restoring maternal T cell imbalance. These findings demonstrate an essential role for Treg cells in mediating P4 effects at implantation, and indicate that Treg cells are a sensitive and critical effector mechanism through which P4 drives uterine receptivity to support robust placental development and fetal growth.
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Published: June 8, 2023
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© 2023, Green et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.