Nodal Signaling Regulates Germ Cell Development and Establishment of Seminiferous Cords in the Human Fetal Testis

Anne Jørgensen, Joni Macdonald, John E Nielsen, Karen R Kilcoyne, Signe Perlman, Lene Lundvall, Lea Langhoff Thuesen, Kristine Juul Hare, Hanne Frederiksen, Anna-Maria Andersson, Niels E Skakkebæk, Anders Juul, Richard M Sharpe, Ewa Rajpert-De Meyts, Rod T Mitchell

29 Citationer (Scopus)

Abstract

Disruption of human fetal testis development is widely accepted to underlie testicular germ cell cancer (TGCC) origin and additional disorders within testicular dysgenesis syndrome (TDS). However, the mechanisms for the development of testicular dysgenesis in humans are unclear. We used ex vivo culture and xenograft approaches to investigate the importance of Nodal and Activin signaling in human fetal testis development. Inhibition of Nodal, and to some extent Activin, signaling disrupted seminiferous cord formation, abolished AMH expression, reduced androgen secretion, and decreased gonocyte numbers. Subsequent xenografting of testicular tissue rescued the disruptive effects on seminiferous cords and somatic cells but not germ cell effects. Stimulation of Nodal signaling increased the number of germ cells expressing pluripotency factors, and these persisted after xenografting. Our findings suggest a key role for Nodal signaling in the regulation of gonocyte differentiation and early human testis development with implications for the understanding of TGCC and TDS origin.

OriginalsprogEngelsk
TidsskriftCell Reports
Vol/bind25
Udgave nummer7
Sider (fra-til)1924-1937.e4
DOI
StatusUdgivet - 13 nov. 2018

Fingeraftryk

Dyk ned i forskningsemnerne om 'Nodal Signaling Regulates Germ Cell Development and Establishment of Seminiferous Cords in the Human Fetal Testis'. Sammen danner de et unikt fingeraftryk.

Citationsformater