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

Anne Jørgensen | Zendy; Joni Macdonald | Zendy; John E. Nielsen | Zendy; Karen Kilcoyne | Zendy; Signe Perlman | Zendy; Lene Lundvall | Zendy; Lea Langhoff Thuesen | Zendy; Kristine Juul Hare | Zendy; Hanne Frederiksen | Zendy; AnnaMaria Andersson | Zendy; Niels E. Skakkebæk | Zendy; Anders Juul | Zendy; Richard M. Sharpe | Zendy; Ewa RajpertDe Meyts | Zendy; Rod T. Mitchell | Zendy

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

Author(s) -

Anne Jørgensen,

Joni Macdonald,

John E. Nielsen,

Karen Kilcoyne,

Signe Perlman,

Lene Lundvall,

Lea Langhoff Thuesen,

Kristine Juul Hare,

Hanne Frederiksen,

AnnaMaria Andersson,

Niels E. Skakkebæk,

Anders Juul,

Richard M. Sharpe,

Ewa RajpertDe Meyts,

Rod T. Mitchell

Publication year - 2018

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2018.10.064

Subject(s) - gonocyte , biology , nodal , nodal signaling , somatic cell , germ cell , medicine , endocrinology , dysgenesis , fetus , testicle , microbiology and biotechnology , sertoli cell , embryogenesis , embryo , spermatogenesis , anatomy , gene , genetics , pregnancy , gastrulation

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.

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