Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Activin A determines steroid levels and composition in the fetal testis

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Hypophosphatemic Hypovitaminosis D induces Osteomalacia in the adult female rat

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Association of In Utero Persistent Organic Pollutant Exposure with Placental Thyroid Hormones

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Roles of RFRP-3 in the Daily and Seasonal Regulation of Reproductive Activity in Female Syrian Hamsters

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Chemical UV Filters Mimic the Effect of Progesterone on Ca(2+) Signaling in Human Sperm Cells

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  5. Rac1 in Muscle Is Dispensable for Improved Insulin Action After Exercise in Mice

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Reproductive Hormones During Pubertal Transition in Girls with Transient Thelarche

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Levels of endocrine-disrupting chemicals are associated with changes in the peri-pubertal epigenome

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Application of miRNAs in the diagnosis and monitoring of testicular germ cell tumours

    Publikation: Bidrag til tidsskriftReviewForskningpeer review

  • Penny A F Whiley
  • Liza O'Donnell
  • Sarah C Moody
  • David J Handelsman
  • Julia C Young
  • Elizabeth A Richards
  • Kristian Almstrup
  • Patrick S Western
  • Kate L Loveland
Vis graf over relationer

Activin A promotes fetal mouse testis development, including driving Sertoli cell proliferation and cord morphogenesis, but its mechanisms of action are undefined. We performed ribonucleic acid sequencing (RNA-seq) on testicular somatic cells from fetal activin A-deficient mice (Inhba KO) and wildtype littermates at embryonic day (E) E13.5 and E15.5. Analysis of whole gonads provided validation, and cultures with a pathway inhibitor discerned acute from chronic effects of altered activin A bioactivity. Activin A deficiency predominantly affects the Sertoli cell transcriptome. New candidate targets include Minar1, Sel1l3, Vnn1, Sfrp4, Masp1, Nell1, Tthy1 and Prss12. Importantly, the testosterone (T) biosynthetic enzymes present in fetal Sertoli cells, Hsd17b1 and Hsd17b3, were identified as activin-responsive. Activin-deficient testes contained elevated androstenedione (A4), displayed an Inhba gene dose-dependent A4/T ratio, and contained 11-keto androgens. The remarkable accumulation of lipid droplets in both Sertoli and germ cells at E15.5 indicated impaired lipid metabolism in the absence of activin A. This demonstrated for the first time that activin A acts on Sertoli cells to determine local steroid production during fetal testis development. These outcomes reveal how compounds that perturb fetal steroidogenesis can function through cell-specific mechanisms and can indicate how altered activin levels in utero may impact testis development.

OriginalsprogEngelsk
TidsskriftEndocrinology
Vol/bind161
Udgave nummer7
Sider (fra-til)1-16
ISSN0013-7227
DOI
StatusUdgivet - 1 jul. 2020

Bibliografisk note

© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

ID: 59983970