A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Testosterone Exposure During Fetal Masculinization Programming Window Determines the Kidney Size in Adult Mice
Tekijät: 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
Julkaisuvuosi: 2026
Lehti: FASEB Journal
Artikkelin numero: e71724
Vuosikerta: 40
Numero: 7
ISSN: 0892-6638
eISSN: 1530-6860
DOI: https://doi.org/10.1096/fj.202500761RR
Julkaisun avoimuus kirjaamishetkellä: Avoimesti saatavilla
Julkaisukanavan avoimuus : Osittain avoin julkaisukanava
Verkko-osoite: https://doi.org/10.1096/fj.202500761rr
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/522945379
Rinnakkaistallenteen lisenssi: CC BY
Rinnakkaistallennetun julkaisun versio: Kustantajan versio
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.
Ladattava julkaisu This is an electronic reprint of the original article. |
Julkaisussa olevat rahoitustiedot:
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.