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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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-02-01
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| 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. |
| format | Article |
| id | doaj-art-d2da360f55d14d43842ab70c3d24ef7e |
| institution | OA Journals |
| issn | 2948-1716 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| 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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