Mimicking women’s endocrine milieu in mice for women’s health-related studies

Abstract To improve preclinical studies and their translation, patient-derived xenografts (PDXs) are increasingly used. They have human-specific tumor characteristics and reflect intra and inter-tumor heterogeneity. However, the endocrine milieu differs between humans and host mice. In light of sex-...

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Main Authors: Céline Constantin, Daria Matvienko, Csaba László, Valentina Scabia, Laura Battista, Pierre-Alain Binz, Stephen J. Bruce, Cathrin Brisken
Format: Article
Language:English
Published: Nature Portfolio 2025-02-01
Series:npj Women's Health
Online Access:https://doi.org/10.1038/s44294-025-00060-4
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author Céline Constantin
Daria Matvienko
Csaba László
Valentina Scabia
Laura Battista
Pierre-Alain Binz
Stephen J. Bruce
Cathrin Brisken
author_facet Céline Constantin
Daria Matvienko
Csaba László
Valentina Scabia
Laura Battista
Pierre-Alain Binz
Stephen J. Bruce
Cathrin Brisken
author_sort Céline Constantin
collection DOAJ
description Abstract To improve preclinical studies and their translation, patient-derived xenografts (PDXs) are increasingly used. They have human-specific tumor characteristics and reflect intra and inter-tumor heterogeneity. However, the endocrine milieu differs between humans and host mice. In light of sex-specific cancer biology and a rise in endocrine-related cancers there is an urgent need to correctly reflect the hormonal milieu in PDX models. We show that female mice of NOD.Cg-Prkdc scid Il2rg tm1Wjl /SzJ (NSG) strain widely used for PDXs has 17-β-estradiol (E2) and testosterone (T) levels comparable to C57Bl6 females but higher progesterone (P4) levels. E2 levels are comparable, T levels are lower and P4 levels higher than those observed in postmenopausal women. Ovariectomy increases T to levels observed in postmenopausal women. Subcutaneous E2 and combined E2/P4 silicon pellets provide NSG females with premenopausal ovarian hormone levels. These procedures humanize the endocrine environment of experimental animals, improving PDX relevance in women’s health-related research.
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series npj Women's Health
spelling doaj-art-d2da360f55d14d43842ab70c3d24ef7e2025-08-20T01:56:09ZengNature Portfolionpj Women's Health2948-17162025-02-01311910.1038/s44294-025-00060-4Mimicking women’s endocrine milieu in mice for women’s health-related studiesCéline Constantin0Daria Matvienko1Csaba László2Valentina Scabia3Laura Battista4Pierre-Alain Binz5Stephen J. Bruce6Cathrin Brisken7Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL)Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL)Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL)Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL)Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL)Clinical Chemistry Laboratory, Centre Hospitalier Universitaire Vaudois (CHUV)Clinical Chemistry Laboratory, Centre Hospitalier Universitaire Vaudois (CHUV)Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL)Abstract To improve preclinical studies and their translation, patient-derived xenografts (PDXs) are increasingly used. They have human-specific tumor characteristics and reflect intra and inter-tumor heterogeneity. However, the endocrine milieu differs between humans and host mice. In light of sex-specific cancer biology and a rise in endocrine-related cancers there is an urgent need to correctly reflect the hormonal milieu in PDX models. We show that female mice of NOD.Cg-Prkdc scid Il2rg tm1Wjl /SzJ (NSG) strain widely used for PDXs has 17-β-estradiol (E2) and testosterone (T) levels comparable to C57Bl6 females but higher progesterone (P4) levels. E2 levels are comparable, T levels are lower and P4 levels higher than those observed in postmenopausal women. Ovariectomy increases T to levels observed in postmenopausal women. Subcutaneous E2 and combined E2/P4 silicon pellets provide NSG females with premenopausal ovarian hormone levels. These procedures humanize the endocrine environment of experimental animals, improving PDX relevance in women’s health-related research.https://doi.org/10.1038/s44294-025-00060-4
spellingShingle Céline Constantin
Daria Matvienko
Csaba László
Valentina Scabia
Laura Battista
Pierre-Alain Binz
Stephen J. Bruce
Cathrin Brisken
Mimicking women’s endocrine milieu in mice for women’s health-related studies
npj Women's Health
title Mimicking women’s endocrine milieu in mice for women’s health-related studies
title_full Mimicking women’s endocrine milieu in mice for women’s health-related studies
title_fullStr Mimicking women’s endocrine milieu in mice for women’s health-related studies
title_full_unstemmed Mimicking women’s endocrine milieu in mice for women’s health-related studies
title_short Mimicking women’s endocrine milieu in mice for women’s health-related studies
title_sort mimicking women s endocrine milieu in mice for women s health related studies
url https://doi.org/10.1038/s44294-025-00060-4
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