Interleukin 11 blockade during mid to late gestation does not affect maternal blood pressure, pregnancy viability or subsequent fertility in mice

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Interleukin (IL)11 is a crucial regulator during the initiation of pregnancy in humans and mice. Elevated levels are detected in serum, placenta and decidua of women with pre-eclampsia. Elevated IL11 during placentation recapitulates pre-eclampsia in mice, although withdrawal rescues pre-eclampsia features, suggesting that IL11 could provide a novel therapeutic target. The aim of this study was to determine the safety profile of an IL11 antagonist ligated to polyethylene glycol (PEGIL11A) during pregnancy in mice. Blocking IL11 signalling during mid to late gestation pregnancy in mice did not affect pregnancy viability, or alter placental or fetal weight, or morphology. Importantly, decidual area remained unchanged. PEGIL11A did not affect maternal blood pressure, urinary protein or term pup weight. PEGIL11A administration to non-pregnant mice did not affect subsequent fertility; there was no difference in number of implantation sites, or placental or fetal weight between PEGIL11A and PEG-treated mice. These data show that blocking IL11Rα during placentation does not alter the placenta, decidua, fetus, maternal blood pressure or kidneys. These findings highlight the potential of IL11 signalling inhibition as a safe therapy to alleviate pre-eclampsia symptoms and demonstrate the potential for IL11 inhibition as a novel fertility-preserving therapy for women with cancer.

Original languageEnglish
Pages (from-to)250-258
Number of pages9
JournalReproductive BioMedicine Online
Volume36
Issue number3
DOIs
Publication statusPublished - 1 Mar 2018

Keywords

  • Cytokines
  • Fertility
  • Placenta
  • Pre-eclampsia
  • Pregnancy

Cite this

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title = "Interleukin 11 blockade during mid to late gestation does not affect maternal blood pressure, pregnancy viability or subsequent fertility in mice",
abstract = "Interleukin (IL)11 is a crucial regulator during the initiation of pregnancy in humans and mice. Elevated levels are detected in serum, placenta and decidua of women with pre-eclampsia. Elevated IL11 during placentation recapitulates pre-eclampsia in mice, although withdrawal rescues pre-eclampsia features, suggesting that IL11 could provide a novel therapeutic target. The aim of this study was to determine the safety profile of an IL11 antagonist ligated to polyethylene glycol (PEGIL11A) during pregnancy in mice. Blocking IL11 signalling during mid to late gestation pregnancy in mice did not affect pregnancy viability, or alter placental or fetal weight, or morphology. Importantly, decidual area remained unchanged. PEGIL11A did not affect maternal blood pressure, urinary protein or term pup weight. PEGIL11A administration to non-pregnant mice did not affect subsequent fertility; there was no difference in number of implantation sites, or placental or fetal weight between PEGIL11A and PEG-treated mice. These data show that blocking IL11Rα during placentation does not alter the placenta, decidua, fetus, maternal blood pressure or kidneys. These findings highlight the potential of IL11 signalling inhibition as a safe therapy to alleviate pre-eclampsia symptoms and demonstrate the potential for IL11 inhibition as a novel fertility-preserving therapy for women with cancer.",
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author = "Amy Winship and Ellen Menkhorst and {Van Sinderen}, Michelle and Evdokia Dimitriadis",
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Interleukin 11 blockade during mid to late gestation does not affect maternal blood pressure, pregnancy viability or subsequent fertility in mice. / Winship, Amy; Menkhorst, Ellen; Van Sinderen, Michelle; Dimitriadis, Evdokia.

In: Reproductive BioMedicine Online, Vol. 36, No. 3, 01.03.2018, p. 250-258.

Research output: Contribution to journalArticleResearchpeer-review

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AB - Interleukin (IL)11 is a crucial regulator during the initiation of pregnancy in humans and mice. Elevated levels are detected in serum, placenta and decidua of women with pre-eclampsia. Elevated IL11 during placentation recapitulates pre-eclampsia in mice, although withdrawal rescues pre-eclampsia features, suggesting that IL11 could provide a novel therapeutic target. The aim of this study was to determine the safety profile of an IL11 antagonist ligated to polyethylene glycol (PEGIL11A) during pregnancy in mice. Blocking IL11 signalling during mid to late gestation pregnancy in mice did not affect pregnancy viability, or alter placental or fetal weight, or morphology. Importantly, decidual area remained unchanged. PEGIL11A did not affect maternal blood pressure, urinary protein or term pup weight. PEGIL11A administration to non-pregnant mice did not affect subsequent fertility; there was no difference in number of implantation sites, or placental or fetal weight between PEGIL11A and PEG-treated mice. These data show that blocking IL11Rα during placentation does not alter the placenta, decidua, fetus, maternal blood pressure or kidneys. These findings highlight the potential of IL11 signalling inhibition as a safe therapy to alleviate pre-eclampsia symptoms and demonstrate the potential for IL11 inhibition as a novel fertility-preserving therapy for women with cancer.

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