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Testosterone Exposure During Fetal Masculinization Programming Window Determines the Kidney Size in Adult Mice




TekijätJunnila, 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

Julkaisuvuosi2026

Lehti: FASEB Journal

Artikkelin numeroe71724

Vuosikerta40

Numero7

ISSN0892-6638

eISSN1530-6860

DOIhttps://doi.org/10.1096/fj.202500761RR

Julkaisun avoimuus kirjaamishetkelläAvoimesti saatavilla

Julkaisukanavan avoimuus Osittain avoin julkaisukanava

Verkko-osoitehttps://doi.org/10.1096/fj.202500761rr

Rinnakkaistallenteen osoitehttps://research.utu.fi/converis/portal/detail/Publication/522945379

Rinnakkaistallenteen lisenssiCC BY

Rinnakkaistallennetun julkaisun versioKustantajan versio


Tiivistelmä

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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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.


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