On the development of extragonadal and gonadal human germ cells.

A Marijne Heeren,Nannan He,Susana M Chuva De Sousa Lopes,Angelique Goercharn-Ramlal,Matthias S Roost,Maria M Gomes Fernandes,Lucette A J Van Der Westerlaken,Aline F De Souza,Liesbeth Van Iperen

doi:10.1242/bio.013847

A Marijne Heeren, Nannan He + Show 7 more

Open Access

https://doi.org/10.1242/bio.013847

Copy DOI

Abstract

ABSTRACTHuman germ cells originate in an extragonadal location and have to migrate to colonize the gonadal primordia at around seven weeks of gestation (W7, or five weeks post conception). Many germ cells are lost along the way and should enter apoptosis, but some escape and can give rise to extragonadal germ cell tumors. Due to the common somatic origin of gonads and adrenal cortex, we investigated whether ectopic germ cells were present in the human adrenals. Germ cells expressing DDX4 and/or POU5F1 were present in male and female human adrenals in the first and second trimester. However, in contrast to what has been described in mice, where ‘adrenal’ and ‘ovarian’ germ cells seem to enter meiosis in synchrony, we were unable to observe meiotic entry in human ‘adrenal’ germ cells until W22. By contrast, ‘ovarian’ germ cells at W22 showed a pronounced asynchronous meiotic entry. Interestingly, we observed that immature POU5F1+ germ cells in both first and second trimester ovaries still expressed the neural crest marker TUBB3, reminiscent of their migratory phase. Our findings highlight species-specific differences in early gametogenesis between mice and humans. We report the presence of a population of ectopic germ cells in the human adrenals during development.

Highlights

In humans, primordial germ cells (PGCs) originate outside the gonadal primordia, in the posterior part of the yolk sac, close to the allantois and hindgut wall and undergo a phase of proliferation and migration towards the gonadal ridge
Germ cells were present in several ectopic locations in female mice embryos First, we investigated the presence of germ cells at ectopic locations in mice at embryonic day (E)15.5 when basically all female gonadal germ cells have entered meiosis (Bullejos and Koopman, 2004)
Germ cells were present in human fetal male and female adrenals we investigated the presence of germ cells in human fetal adrenal glands in females and in males (Table S1) by immunofluorescence for DDX4 and the early germ cell marker POU5F1

Summary

Introduction

Primordial germ cells (PGCs) originate outside the gonadal primordia, in the posterior part of the yolk sac, close to the allantois and hindgut wall and undergo a phase of proliferation and migration towards the gonadal ridge EPnrot fo.fDr. Gynaecology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. Medical Center, Amsterdam, De Boelelaan 1118, 1081 HZ Amsterdam, The Netherlands. §These authors are equal first authors and contributed to this work. These PGCs reach gonadal primordia around week 7 of gestation (W7, or week 5 post conception) to become enclosed in either seminiferous tubules or ovarian cords, respectively in male and female embryos (Heeren et al, 2015)

Methods

Results

Conclusion