Publication

Prednisolone in early pregnancy inhibits regulatory T cell generation and alters fetal and placental development in mice

Kieffer, T. E. C., Chin, P. Y., Green, E. S., Moldenhauer, L. M., Prins, J. R. & Robertson, S. A., May-2020, In : Molecular human reproduction. 26, 5, p. 340-352 13 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Kieffer, T. E. C., Chin, P. Y., Green, E. S., Moldenhauer, L. M., Prins, J. R., & Robertson, S. A. (2020). Prednisolone in early pregnancy inhibits regulatory T cell generation and alters fetal and placental development in mice. Molecular human reproduction, 26(5), 340-352. https://doi.org/10.1093/molehr/gaaa019

Author

Kieffer, Tom E C ; Chin, Peck Y ; Green, Ella S ; Moldenhauer, Lachlan M ; Prins, Jelmer R ; Robertson, Sarah A. / Prednisolone in early pregnancy inhibits regulatory T cell generation and alters fetal and placental development in mice. In: Molecular human reproduction. 2020 ; Vol. 26, No. 5. pp. 340-352.

Harvard

Kieffer, TEC, Chin, PY, Green, ES, Moldenhauer, LM, Prins, JR & Robertson, SA 2020, 'Prednisolone in early pregnancy inhibits regulatory T cell generation and alters fetal and placental development in mice', Molecular human reproduction, vol. 26, no. 5, pp. 340-352. https://doi.org/10.1093/molehr/gaaa019

Standard

Prednisolone in early pregnancy inhibits regulatory T cell generation and alters fetal and placental development in mice. / Kieffer, Tom E C; Chin, Peck Y; Green, Ella S; Moldenhauer, Lachlan M; Prins, Jelmer R; Robertson, Sarah A.

In: Molecular human reproduction, Vol. 26, No. 5, 05.2020, p. 340-352.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Kieffer TEC, Chin PY, Green ES, Moldenhauer LM, Prins JR, Robertson SA. Prednisolone in early pregnancy inhibits regulatory T cell generation and alters fetal and placental development in mice. Molecular human reproduction. 2020 May;26(5):340-352. https://doi.org/10.1093/molehr/gaaa019


BibTeX

@article{eb3e67fd9a38423798a351a98d5723a6,
title = "Prednisolone in early pregnancy inhibits regulatory T cell generation and alters fetal and placental development in mice",
abstract = "Corticosteroids have been utilised in the assisted reproduction setting with the expectation of suppressing aberrant immune activation and improving fertility in women. However the effects of corticosteroids on fertility, and on pregnancy and offspring outcomes, are unclear. In this study, mice were administered prednisolone (1 mg/kg) or PBS daily in the pre-implantation phase, and effects on the adaptive immune response, the implantation rate, fetal development, and postnatal outcomes were investigated. Prednisolone disrupted the expected expansion of CD4+ T cells in early pregnancy, inhibiting generation of both regulatory T cells (Treg cells) and effector T cells and suppressing IFNG required for T cell functional competence. Prednisolone caused an 8-20{\%} increase in the embryo implantation rate and increased the number of viable pups per litter. In late gestation, fetal and placental weights were reduced in a litter size-dependent manner, and the canonical inverse relationship between litter size and fetal weight was lost. The duration of pregnancy was extended by ~0.5 day and birth weight was reduced by ~5{\%} after prednisolone treatment. Viability of prednisolone-exposed offspring was comparable to controls, but body weight was altered in adulthood, particularly in male offspring. Thus, while prednisolone given in the pre-implantation phase in mice increases maternal receptivity to implantation and resource investment in fetal growth, there is a trade-off in long-term consequences for fetal development, birth weight and offspring health. These effects are associated with, and likely caused by, prednisolone suppression of the adaptive immune response at the outset of pregnancy.",
keywords = "prednisolone, corticosteroids, immune suppression, immune tolerance, regulatory T cells, implantation, fetal growth, fetal programming, parturition, NATURAL-KILLER-CELLS, IFN-GAMMA PRODUCTION, EMBRYO IMPLANTATION, IMMUNE-RESPONSE, PRENATAL EXPOSURE, INTERFERON-GAMMA, GLUCOCORTICOIDS, CORTICOSTEROIDS, EXPRESSION, MECHANISMS",
author = "Kieffer, {Tom E C} and Chin, {Peck Y} and Green, {Ella S} and Moldenhauer, {Lachlan M} and Prins, {Jelmer R} and Robertson, {Sarah A}",
note = "{\circledC} The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.",
year = "2020",
month = "5",
doi = "10.1093/molehr/gaaa019",
language = "English",
volume = "26",
pages = "340--352",
journal = "Molecular human reproduction",
issn = "1360-9947",
publisher = "Oxford University Press",
number = "5",

}

RIS

TY - JOUR

T1 - Prednisolone in early pregnancy inhibits regulatory T cell generation and alters fetal and placental development in mice

AU - Kieffer, Tom E C

AU - Chin, Peck Y

AU - Green, Ella S

AU - Moldenhauer, Lachlan M

AU - Prins, Jelmer R

AU - Robertson, Sarah A

N1 - © The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

PY - 2020/5

Y1 - 2020/5

N2 - Corticosteroids have been utilised in the assisted reproduction setting with the expectation of suppressing aberrant immune activation and improving fertility in women. However the effects of corticosteroids on fertility, and on pregnancy and offspring outcomes, are unclear. In this study, mice were administered prednisolone (1 mg/kg) or PBS daily in the pre-implantation phase, and effects on the adaptive immune response, the implantation rate, fetal development, and postnatal outcomes were investigated. Prednisolone disrupted the expected expansion of CD4+ T cells in early pregnancy, inhibiting generation of both regulatory T cells (Treg cells) and effector T cells and suppressing IFNG required for T cell functional competence. Prednisolone caused an 8-20% increase in the embryo implantation rate and increased the number of viable pups per litter. In late gestation, fetal and placental weights were reduced in a litter size-dependent manner, and the canonical inverse relationship between litter size and fetal weight was lost. The duration of pregnancy was extended by ~0.5 day and birth weight was reduced by ~5% after prednisolone treatment. Viability of prednisolone-exposed offspring was comparable to controls, but body weight was altered in adulthood, particularly in male offspring. Thus, while prednisolone given in the pre-implantation phase in mice increases maternal receptivity to implantation and resource investment in fetal growth, there is a trade-off in long-term consequences for fetal development, birth weight and offspring health. These effects are associated with, and likely caused by, prednisolone suppression of the adaptive immune response at the outset of pregnancy.

AB - Corticosteroids have been utilised in the assisted reproduction setting with the expectation of suppressing aberrant immune activation and improving fertility in women. However the effects of corticosteroids on fertility, and on pregnancy and offspring outcomes, are unclear. In this study, mice were administered prednisolone (1 mg/kg) or PBS daily in the pre-implantation phase, and effects on the adaptive immune response, the implantation rate, fetal development, and postnatal outcomes were investigated. Prednisolone disrupted the expected expansion of CD4+ T cells in early pregnancy, inhibiting generation of both regulatory T cells (Treg cells) and effector T cells and suppressing IFNG required for T cell functional competence. Prednisolone caused an 8-20% increase in the embryo implantation rate and increased the number of viable pups per litter. In late gestation, fetal and placental weights were reduced in a litter size-dependent manner, and the canonical inverse relationship between litter size and fetal weight was lost. The duration of pregnancy was extended by ~0.5 day and birth weight was reduced by ~5% after prednisolone treatment. Viability of prednisolone-exposed offspring was comparable to controls, but body weight was altered in adulthood, particularly in male offspring. Thus, while prednisolone given in the pre-implantation phase in mice increases maternal receptivity to implantation and resource investment in fetal growth, there is a trade-off in long-term consequences for fetal development, birth weight and offspring health. These effects are associated with, and likely caused by, prednisolone suppression of the adaptive immune response at the outset of pregnancy.

KW - prednisolone

KW - corticosteroids

KW - immune suppression

KW - immune tolerance

KW - regulatory T cells

KW - implantation

KW - fetal growth

KW - fetal programming

KW - parturition

KW - NATURAL-KILLER-CELLS

KW - IFN-GAMMA PRODUCTION

KW - EMBRYO IMPLANTATION

KW - IMMUNE-RESPONSE

KW - PRENATAL EXPOSURE

KW - INTERFERON-GAMMA

KW - GLUCOCORTICOIDS

KW - CORTICOSTEROIDS

KW - EXPRESSION

KW - MECHANISMS

U2 - 10.1093/molehr/gaaa019

DO - 10.1093/molehr/gaaa019

M3 - Article

VL - 26

SP - 340

EP - 352

JO - Molecular human reproduction

JF - Molecular human reproduction

SN - 1360-9947

IS - 5

ER -

ID: 120086027