title: On the development of extragonadal and gonadal human germ cells.
abstract: Human 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.
authors.affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, The Netherlands.
authors.forename: A Marijne
authors.initials: AM
authors.lastname: Heeren
authors.affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, The Netherlands.
authors.forename: Nannan
authors.initials: N
authors.lastname: He
authors.affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, The Netherlands Dept. of Veterinary Medicine, Faculty Animal Sciences and Food Engineering, University of São Paulo, Av. Duque de Caxias Norte 225, 13630-000 SP Pirassununga, Brazil Dept. of Surgery, Faculty Veterinary Medicine and Animal Sciences, University of São Paulo, Av. Prof. Dr. Orlando Marques Paiva 87, 05508-270 SP São Paulo, Brazil.
authors.forename: Aline F
authors.initials: AF
authors.lastname: de Souza
authors.affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, The Netherlands.
authors.forename: Angelique
authors.initials: A
authors.lastname: Goercharn-Ramlal
authors.affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, The Netherlands.
authors.forename: Liesbeth
authors.initials: L
authors.lastname: van Iperen
authors.affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, The Netherlands.
authors.forename: Matthias S
authors.initials: MS
authors.lastname: Roost
authors.affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, The Netherlands.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Gomes Fernandes
authors.affiliation: Department of Gynaecology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
authors.forename: Lucette A J
authors.initials: LA
authors.lastname: van der Westerlaken
authors.affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, The Netherlands Department for Reproductive Medicine, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium lopes@lumc.nl.
authors.forename: Susana M
authors.initials: SM
authors.lastname: Chuva de Sousa Lopes
keywords: Adrenals; Development; Ectopic; Fetal; Germ cells; Human; Meiosis; Ovaries
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