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

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@article{45d3826961314fcfbc412e314473b599,
title = "Nodal Signaling Regulates Germ Cell Development and Establishment of Seminiferous Cords in the Human Fetal Testis",
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.",
author = "Anne J{\o}rgensen and Joni Macdonald and Nielsen, {John E} and Kilcoyne, {Karen R} and Signe Perlman and Lene Lundvall and {Langhoff Thuesen}, Lea and {Juul Hare}, Kristine and Hanne Frederiksen and Anna-Maria Andersson and Skakkeb{\ae}k, {Niels E} and Anders Juul and Sharpe, {Richard M} and {Rajpert-De Meyts}, Ewa and Mitchell, {Rod T}",
note = "Copyright {\circledC} 2018 The Author(s). Published by Elsevier Inc. All rights reserved.",
year = "2018",
month = "11",
day = "13",
doi = "10.1016/j.celrep.2018.10.064",
language = "English",
volume = "25",
pages = "1924--1937.e4",
journal = "Cell Reports",
publisher = "Cell Press",
number = "7",

}

RIS

TY - JOUR

T1 - Nodal Signaling Regulates Germ Cell Development and Establishment of Seminiferous Cords in the Human Fetal Testis

AU - Jørgensen, Anne

AU - Macdonald, Joni

AU - Nielsen, John E

AU - Kilcoyne, Karen R

AU - Perlman, Signe

AU - Lundvall, Lene

AU - Langhoff Thuesen, Lea

AU - Juul Hare, Kristine

AU - Frederiksen, Hanne

AU - Andersson, Anna-Maria

AU - Skakkebæk, Niels E

AU - Juul, Anders

AU - Sharpe, Richard M

AU - Rajpert-De Meyts, Ewa

AU - Mitchell, Rod T

N1 - Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

PY - 2018/11/13

Y1 - 2018/11/13

N2 - 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.

AB - 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.

U2 - 10.1016/j.celrep.2018.10.064

DO - 10.1016/j.celrep.2018.10.064

M3 - Journal article

VL - 25

SP - 1924-1937.e4

JO - Cell Reports

JF - Cell Reports

IS - 7

ER -

ID: 55630657