A1 Refereed original research article in a scientific journal
Testosterone Exposure During Fetal Masculinization Programming Window Determines the Kidney Size in Adult Mice
Authors: Junnila, Arttu; Rytkönen, Kalle T.; Martinez‐Nieto, Guillermo; Perk, Mats; Mäkelä, Otto; Li, Hao; Airaksinen, Jenni; Hyötyläinen, Ida; Mehtovuori, Oliver; Laiho, Asta; Ohlsson, Claes; Elo, Laura L.; Kuure, Satu; Poutanen, Matti; Sipilä, Petra
Publication year: 2026
Journal: FASEB Journal
Article number: e71724
Volume: 40
Issue: 7
ISSN: 0892-6638
eISSN: 1530-6860
DOI: https://doi.org/10.1096/fj.202500761RR
Publication's open availability at the time of reporting: Open Access
Publication channel's open availability : Partially Open Access publication channel
Web address : https://doi.org/10.1096/fj.202500761rr
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/522945379
Self-archived copy's licence: CC BY
Self-archived copy's version: Publisher`s PDF
Kidney size is sex-dimorphic and regulated by androgens in adult humans and mice. However, the effects of developmental androgen deficiency on kidneys remain elusive. We hypothesized that androgens program future kidney growth during fetal development. Male mice lacking the main testosterone-producing enzyme HSD17B3 had reduced testosterone at embryonic day 15.5, but the concentrations increased by E18.5, creating a short time window of androgen deficiency resulting in reduced kidney size in adult males. In male Hsd17b3−/− kidneys, nephron development was qualitatively normal, but the number of glomeruli and proliferation of proximal tubules were reduced, as was proximal tubule size in adults. Testosterone supplementation at E14.5–17.5 normalized the renal size in adult Hsd17b3−/− males. Our data suggest that androgen receptor and HNF4A jointly regulate IGFBP5, putatively influencing FOXO1 and mTOR signaling to promote male-specific kidney growth in the fetal period. In conclusion, we have identified a novel developmental programming effect on male kidneys, where fetal androgen deficiency reduces kidney growth and androgen responsiveness in adult males.
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Funding information in the publication:
Sigrid Juséliuksen Säätiö (Sigrid Jusélius Stiftelse), 10.13039/501100006306. Jalmari ja Rauha Ahokkaan Säätiö (Jalmari and Rauha Ahokas Foundation), 10.13039/100010125. Turun Yliopistosäätiö (Turku University Foundation), 10.13039/501100022793. Organon RD Finland.