The progesterone derivative dydrogesterone abrogates murine stress-triggered abortion by inducing a Th2 biased local immune response

Ricarda Joachim, Ana Claudia Zenclussen, Beata Polgar, Alison J. Douglas, Stefan Fest, Maike Knackstedt, Burghard F. Klapp, Petra Clara Arck

Research output: Contribution to journalArticle

97 Citations (Scopus)

Abstract

Stress is known to induce abortions in mice and humans, putatively via increased levels of abortogenic Th1 cytokines and a decrease of progesterone. Adequate levels of progesterone exert an antiabortive response through binding to the progesterone-receptor, which induces the release of progesterone-induced blocking factor (PIBF) from lymphocytes. PIBF is highly pregnancy-protective by induction of a Th2 biased immune activity. The aim of this study was to investigate the effect of the progesterone derivative dydrogesterone (6-dehydro-retroprogesterone) in stress-triggered murine abortion. DBA/2J-mated CBA/J female mice were randomized in different groups: two groups were treated with different dydrogesterone dosages in a single injection before exposure to sound stress on Day 5 of pregnancy, one group was exposed to stress without dydrogesterone treatment, the fourth group received no stress and no dydrogesterone. On gestation Day 13, a highly elevated abortion rate was detected in stressed mice compared to control mice. Stressed animals presented lower levels of progesterone and PIBF in plasma and a reduced staining intensity of progesterone receptor at the feto-maternal interface. Injection of dydrogesterone abrogated the effect of stress on the abortion rate. Further, dydrogesterone increased levels of plasma PIBF in stressed mice, but did not affect progesterone levels. Interestingly, dydrogesterone dramatically increased the percentage of IL-4 positive decidual immune cells in stressed mice. Our data suggest that dydrogesterone abrogates stress-triggered abortion by inducing a Th2 biased local immune response.

Original languageEnglish
Pages (from-to)931-940
Number of pages10
JournalSteroids
Volume68
Issue number10-13
DOIs
Publication statusPublished - Nov 2003

Fingerprint

Progesterone
Derivatives
Induced Abortion
Progesterone Receptors
Pregnancy
Plasmas
Injections
Lymphocytes
Interleukin-4
Animals
Mothers
Acoustic waves
Staining and Labeling
Cytokines
blocking factor

Keywords

  • Abortion
  • Interleukin-4
  • Mice
  • Progesterone
  • Progesterone receptor

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Molecular Biology

Cite this

The progesterone derivative dydrogesterone abrogates murine stress-triggered abortion by inducing a Th2 biased local immune response. / Joachim, Ricarda; Zenclussen, Ana Claudia; Polgar, Beata; Douglas, Alison J.; Fest, Stefan; Knackstedt, Maike; Klapp, Burghard F.; Arck, Petra Clara.

In: Steroids, Vol. 68, No. 10-13, 11.2003, p. 931-940.

Research output: Contribution to journalArticle

Joachim, Ricarda ; Zenclussen, Ana Claudia ; Polgar, Beata ; Douglas, Alison J. ; Fest, Stefan ; Knackstedt, Maike ; Klapp, Burghard F. ; Arck, Petra Clara. / The progesterone derivative dydrogesterone abrogates murine stress-triggered abortion by inducing a Th2 biased local immune response. In: Steroids. 2003 ; Vol. 68, No. 10-13. pp. 931-940.
@article{68387948b41e4de097e956d5671dd5d1,
title = "The progesterone derivative dydrogesterone abrogates murine stress-triggered abortion by inducing a Th2 biased local immune response",
abstract = "Stress is known to induce abortions in mice and humans, putatively via increased levels of abortogenic Th1 cytokines and a decrease of progesterone. Adequate levels of progesterone exert an antiabortive response through binding to the progesterone-receptor, which induces the release of progesterone-induced blocking factor (PIBF) from lymphocytes. PIBF is highly pregnancy-protective by induction of a Th2 biased immune activity. The aim of this study was to investigate the effect of the progesterone derivative dydrogesterone (6-dehydro-retroprogesterone) in stress-triggered murine abortion. DBA/2J-mated CBA/J female mice were randomized in different groups: two groups were treated with different dydrogesterone dosages in a single injection before exposure to sound stress on Day 5 of pregnancy, one group was exposed to stress without dydrogesterone treatment, the fourth group received no stress and no dydrogesterone. On gestation Day 13, a highly elevated abortion rate was detected in stressed mice compared to control mice. Stressed animals presented lower levels of progesterone and PIBF in plasma and a reduced staining intensity of progesterone receptor at the feto-maternal interface. Injection of dydrogesterone abrogated the effect of stress on the abortion rate. Further, dydrogesterone increased levels of plasma PIBF in stressed mice, but did not affect progesterone levels. Interestingly, dydrogesterone dramatically increased the percentage of IL-4 positive decidual immune cells in stressed mice. Our data suggest that dydrogesterone abrogates stress-triggered abortion by inducing a Th2 biased local immune response.",
keywords = "Abortion, Interleukin-4, Mice, Progesterone, Progesterone receptor",
author = "Ricarda Joachim and Zenclussen, {Ana Claudia} and Beata Polgar and Douglas, {Alison J.} and Stefan Fest and Maike Knackstedt and Klapp, {Burghard F.} and Arck, {Petra Clara}",
year = "2003",
month = "11",
doi = "10.1016/j.steroids.2003.08.010",
language = "English",
volume = "68",
pages = "931--940",
journal = "Steroids",
issn = "0039-128X",
publisher = "Elsevier Inc.",
number = "10-13",

}

TY - JOUR

T1 - The progesterone derivative dydrogesterone abrogates murine stress-triggered abortion by inducing a Th2 biased local immune response

AU - Joachim, Ricarda

AU - Zenclussen, Ana Claudia

AU - Polgar, Beata

AU - Douglas, Alison J.

AU - Fest, Stefan

AU - Knackstedt, Maike

AU - Klapp, Burghard F.

AU - Arck, Petra Clara

PY - 2003/11

Y1 - 2003/11

N2 - Stress is known to induce abortions in mice and humans, putatively via increased levels of abortogenic Th1 cytokines and a decrease of progesterone. Adequate levels of progesterone exert an antiabortive response through binding to the progesterone-receptor, which induces the release of progesterone-induced blocking factor (PIBF) from lymphocytes. PIBF is highly pregnancy-protective by induction of a Th2 biased immune activity. The aim of this study was to investigate the effect of the progesterone derivative dydrogesterone (6-dehydro-retroprogesterone) in stress-triggered murine abortion. DBA/2J-mated CBA/J female mice were randomized in different groups: two groups were treated with different dydrogesterone dosages in a single injection before exposure to sound stress on Day 5 of pregnancy, one group was exposed to stress without dydrogesterone treatment, the fourth group received no stress and no dydrogesterone. On gestation Day 13, a highly elevated abortion rate was detected in stressed mice compared to control mice. Stressed animals presented lower levels of progesterone and PIBF in plasma and a reduced staining intensity of progesterone receptor at the feto-maternal interface. Injection of dydrogesterone abrogated the effect of stress on the abortion rate. Further, dydrogesterone increased levels of plasma PIBF in stressed mice, but did not affect progesterone levels. Interestingly, dydrogesterone dramatically increased the percentage of IL-4 positive decidual immune cells in stressed mice. Our data suggest that dydrogesterone abrogates stress-triggered abortion by inducing a Th2 biased local immune response.

AB - Stress is known to induce abortions in mice and humans, putatively via increased levels of abortogenic Th1 cytokines and a decrease of progesterone. Adequate levels of progesterone exert an antiabortive response through binding to the progesterone-receptor, which induces the release of progesterone-induced blocking factor (PIBF) from lymphocytes. PIBF is highly pregnancy-protective by induction of a Th2 biased immune activity. The aim of this study was to investigate the effect of the progesterone derivative dydrogesterone (6-dehydro-retroprogesterone) in stress-triggered murine abortion. DBA/2J-mated CBA/J female mice were randomized in different groups: two groups were treated with different dydrogesterone dosages in a single injection before exposure to sound stress on Day 5 of pregnancy, one group was exposed to stress without dydrogesterone treatment, the fourth group received no stress and no dydrogesterone. On gestation Day 13, a highly elevated abortion rate was detected in stressed mice compared to control mice. Stressed animals presented lower levels of progesterone and PIBF in plasma and a reduced staining intensity of progesterone receptor at the feto-maternal interface. Injection of dydrogesterone abrogated the effect of stress on the abortion rate. Further, dydrogesterone increased levels of plasma PIBF in stressed mice, but did not affect progesterone levels. Interestingly, dydrogesterone dramatically increased the percentage of IL-4 positive decidual immune cells in stressed mice. Our data suggest that dydrogesterone abrogates stress-triggered abortion by inducing a Th2 biased local immune response.

KW - Abortion

KW - Interleukin-4

KW - Mice

KW - Progesterone

KW - Progesterone receptor

UR - http://www.scopus.com/inward/record.url?scp=0345735760&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0345735760&partnerID=8YFLogxK

U2 - 10.1016/j.steroids.2003.08.010

DO - 10.1016/j.steroids.2003.08.010

M3 - Article

C2 - 14667986

AN - SCOPUS:0345735760

VL - 68

SP - 931

EP - 940

JO - Steroids

JF - Steroids

SN - 0039-128X

IS - 10-13

ER -