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<p>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 <i>NOD.Cg-Prkdc</i><sup><i>scid</i></sup> <i>Il2rg</i><sup><i>tm1Wjl</i></sup><i>/SzJ (NSG)</i> strain widely used for PDXs has 17-β-estradiol (E2) and testosterone (T) levels comparable to <i>C57Bl6</i> 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 <i>NSG</i> females with premenopausal ovarian hormone levels. These procedures humanize the endocrine environment of experimental animals, improving PDX relevance in women’s health-related research.</p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年2月22日

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  • Céline Constantin,
  • Daria Matvienko,
  • Csaba László,
  • Valentina Scabia,
  • Laura Battista,
  • Pierre-Alain Binz,
  • Stephen J. Bruce,
  • Cathrin Brisken

摘要

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-Prkdcscid Il2rgtm1Wjl/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.