Testosterone exposure shifts female baseline phenotypes toward a male-associated tear-nerve-epithelial state in mice
Abstract
Sex and hormonal status are clinically relevant determinants of ocular-surface physiology, but whether adult androgen exposure shifts multiple components of the ocular surface in parallel remains poorly defined. We compared vehicle-treated female mice with testosterone-treated females and used intact males as a physiological reference rather than as a procedure-matched control. Modified-nucleoside profiling, tear proteomics, corneal and trigeminal ganglion RNA sequencing, corneal flat-mount nerve volumetry, von Frey aesthesiometry, phospho-histone H3 labelling and single-endpoint Krt14-CreERT; CAG-Cytbow lineage tracing were combined to examine the tear-nerve-epithelial system at baseline. Tear collection rate was unchanged, whereas total tear protein concentration and proteomic composition differed between vehicle-treated and testosterone-treated females and shifted toward the intact male reference; 1,052 of 3,125 identified tear proteins were modulated in at least one pairwise comparison. Testosterone-treated females also showed lower central βIII-tubulin-positive nerve-fibre volume and mechanical sensitivity and fewer mitotic epithelial cells than vehicle-treated females, while lineage-labelled epithelial foci showed a qualitatively concordant distribution. Corneal transcriptional responses were substantially broader than those in the trigeminal ganglion. These findings show that adult testosterone exposure is associated with coordinated plasticity across several baseline ocular-surface phenotypes. They establish endocrine status as an important biological variable for experimental design while leaving its consequences for injury and disease to future functional studies.
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BibTeX
@article{feret2026testosterone,
title = {{Testosterone exposure shifts female baseline phenotypes toward a male-associated tear-nerve-epithelial state in mice}},
author = {Nadege Feret and Alicia Caballero Megido and Sarah Pernot and Melissa Girard and Marilou Decoudu and Jana Kindermans and Laura Fichter and Sonia Garcia Llorens and Aurore Attina and Jerome Vialaret and Alexandre David and Vincent Daien and Karine Loulier and Christophe Hirtz and Frederic Michon},
journal = {Scientific Reports},
year = {2026},
month = oct,
doi = {10.1038/s41598-026-73366-1},
url = {https://www.nature.com/articles/s41598-026-73366-1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Testosterone exposure shifts female baseline phenotypes toward a male-associated tear-nerve-epithelial state in mice
AU - Nadege Feret
AU - Alicia Caballero Megido
AU - Sarah Pernot
AU - Melissa Girard
AU - Marilou Decoudu
AU - Jana Kindermans
AU - Laura Fichter
AU - Sonia Garcia Llorens
AU - Aurore Attina
AU - Jerome Vialaret
AU - Alexandre David
AU - Vincent Daien
AU - Karine Loulier
AU - Christophe Hirtz
AU - Frederic Michon
PY - 2026
DA - 2026/10/02
JO - Scientific Reports
DO - 10.1038/s41598-026-73366-1
UR - https://www.nature.com/articles/s41598-026-73366-1
AB - Sex and hormonal status are clinically relevant determinants of ocular-surface physiology, but whether adult androgen exposure shifts multiple components of the ocular surface in parallel remains poorly defined. We compared vehicle-treated female mice with testosterone-treated females and used intact males as a physiological reference rather than as a procedure-matched control. Modified-nucleoside profiling, tear proteomics, corneal and trigeminal ganglion RNA sequencing, corneal flat-mount nerve volumetry, von Frey aesthesiometry, phospho-histone H3 labelling and single-endpoint Krt14-CreERT; CAG-Cytbow lineage tracing were combined to examine the tear-nerve-epithelial system at baseline. Tear collection rate was unchanged, whereas total tear protein concentration and proteomic composition differed between vehicle-treated and testosterone-treated females and shifted toward the intact male reference; 1,052 of 3,125 identified tear proteins were modulated in at least one pairwise comparison. Testosterone-treated females also showed lower central βIII-tubulin-positive nerve-fibre volume and mechanical sensitivity and fewer mitotic epithelial cells than vehicle-treated females, while lineage-labelled epithelial foci showed a qualitatively concordant distribution. Corneal transcriptional responses were substantially broader than those in the trigeminal ganglion. These findings show that adult testosterone exposure is associated with coordinated plasticity across several baseline ocular-surface phenotypes. They establish endocrine status as an important biological variable for experimental design while leaving its consequences for injury and disease to future functional studies.
SN - 2045-2322
ER -