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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Bibliographic Details
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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Summary: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.
ISSN:2948-1716