DYRK1A Overexpression in Mice Downregulates the Gonadotropic Axis and Disturbs Early Stages of Spermatogenesis

Down syndrome (DS) is the most common chromosomal disorder. It is responsible for intellectual disability (ID) and several medical conditions. Although men with DS are thought to be infertile, some spontaneous paternities have been reported. The few studies of the mechanism of infertility in men wit...

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Autores principales:	Rodolphe Dard, Manon Moreau, Estelle Parizot, Farah Ghieh, Leslie Brehier, Nadim Kassis, Valérie Serazin, Antonin Lamaziere, Chrystèle Racine, Nathalie di Clemente, François Vialard, Nathalie Janel
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	Down syndrome infertility DYRK1A Genetics QH426-470
Acceso en línea:	https://doaj.org/article/fd536c0872174e91932bd93bdaa456da
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spelling	oai:doaj.org-article:fd536c0872174e91932bd93bdaa456da2021-11-25T17:42:08ZDYRK1A Overexpression in Mice Downregulates the Gonadotropic Axis and Disturbs Early Stages of Spermatogenesis10.3390/genes121118002073-4425https://doaj.org/article/fd536c0872174e91932bd93bdaa456da2021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4425/12/11/1800https://doaj.org/toc/2073-4425Down syndrome (DS) is the most common chromosomal disorder. It is responsible for intellectual disability (ID) and several medical conditions. Although men with DS are thought to be infertile, some spontaneous paternities have been reported. The few studies of the mechanism of infertility in men with DS are now dated. Recent research in zebrafish has indicated that overexpression of DYRK1A (the protein primarily responsible for ID in DS) impairs gonadogenesis at the embryonic stage. To better ascertain DYRK1A’s role in infertility in DS, we investigated the effect of DYRK1A overexpression in a transgenic mouse model. We found that overexpression of DYRK1A impairs fertility in transgenic male mice. Interestingly, the mechanism in mice differs slightly from that observed in zebrafish but, with disruption of the early stages of spermatogenesis, is similar to that seen in humans. Unexpectedly, we observed hypogonadotropic hypogonadism in the transgenic mice.Rodolphe DardManon MoreauEstelle ParizotFarah GhiehLeslie BrehierNadim KassisValérie SerazinAntonin LamaziereChrystèle RacineNathalie di ClementeFrançois VialardNathalie JanelMDPI AGarticleDown syndromeinfertilityDYRK1AGeneticsQH426-470ENGenes, Vol 12, Iss 1800, p 1800 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Down syndrome infertility DYRK1A Genetics QH426-470
spellingShingle	Down syndrome infertility DYRK1A Genetics QH426-470 Rodolphe Dard Manon Moreau Estelle Parizot Farah Ghieh Leslie Brehier Nadim Kassis Valérie Serazin Antonin Lamaziere Chrystèle Racine Nathalie di Clemente François Vialard Nathalie Janel DYRK1A Overexpression in Mice Downregulates the Gonadotropic Axis and Disturbs Early Stages of Spermatogenesis
description	Down syndrome (DS) is the most common chromosomal disorder. It is responsible for intellectual disability (ID) and several medical conditions. Although men with DS are thought to be infertile, some spontaneous paternities have been reported. The few studies of the mechanism of infertility in men with DS are now dated. Recent research in zebrafish has indicated that overexpression of DYRK1A (the protein primarily responsible for ID in DS) impairs gonadogenesis at the embryonic stage. To better ascertain DYRK1A’s role in infertility in DS, we investigated the effect of DYRK1A overexpression in a transgenic mouse model. We found that overexpression of DYRK1A impairs fertility in transgenic male mice. Interestingly, the mechanism in mice differs slightly from that observed in zebrafish but, with disruption of the early stages of spermatogenesis, is similar to that seen in humans. Unexpectedly, we observed hypogonadotropic hypogonadism in the transgenic mice.
format	article
author	Rodolphe Dard Manon Moreau Estelle Parizot Farah Ghieh Leslie Brehier Nadim Kassis Valérie Serazin Antonin Lamaziere Chrystèle Racine Nathalie di Clemente François Vialard Nathalie Janel
author_facet	Rodolphe Dard Manon Moreau Estelle Parizot Farah Ghieh Leslie Brehier Nadim Kassis Valérie Serazin Antonin Lamaziere Chrystèle Racine Nathalie di Clemente François Vialard Nathalie Janel
author_sort	Rodolphe Dard
title	DYRK1A Overexpression in Mice Downregulates the Gonadotropic Axis and Disturbs Early Stages of Spermatogenesis
title_short	DYRK1A Overexpression in Mice Downregulates the Gonadotropic Axis and Disturbs Early Stages of Spermatogenesis
title_full	DYRK1A Overexpression in Mice Downregulates the Gonadotropic Axis and Disturbs Early Stages of Spermatogenesis
title_fullStr	DYRK1A Overexpression in Mice Downregulates the Gonadotropic Axis and Disturbs Early Stages of Spermatogenesis
title_full_unstemmed	DYRK1A Overexpression in Mice Downregulates the Gonadotropic Axis and Disturbs Early Stages of Spermatogenesis
title_sort	dyrk1a overexpression in mice downregulates the gonadotropic axis and disturbs early stages of spermatogenesis
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/fd536c0872174e91932bd93bdaa456da
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DYRK1A Overexpression in Mice Downregulates the Gonadotropic Axis and Disturbs Early Stages of Spermatogenesis

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