Prokineticin receptor 2 affects GnRH3 neuron ontogeny but not fertility in zebrafish

Abstract Prokineticin receptors (PROKR1 and PROKR2) are G protein-coupled receptors which control human central and peripheral reproductive processes. Importantly, allelic variants of PROKR2 in humans are associated with altered migration of GnRH neurons, resulting in congenital hypogonadotropic hyp...

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Autores principales:	Ivan Bassi, Francesca Luzzani, Federica Marelli, Valeria Vezzoli, Ludovica Cotellessa, David A. Prober, Luca Persani, Yoav Gothilf, Marco Bonomi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a5f5f89f259a47f8945dc2ba1d98ee2d
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spelling	oai:doaj.org-article:a5f5f89f259a47f8945dc2ba1d98ee2d2021-12-02T14:49:43ZProkineticin receptor 2 affects GnRH3 neuron ontogeny but not fertility in zebrafish10.1038/s41598-020-64077-22045-2322https://doaj.org/article/a5f5f89f259a47f8945dc2ba1d98ee2d2020-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-64077-2https://doaj.org/toc/2045-2322Abstract Prokineticin receptors (PROKR1 and PROKR2) are G protein-coupled receptors which control human central and peripheral reproductive processes. Importantly, allelic variants of PROKR2 in humans are associated with altered migration of GnRH neurons, resulting in congenital hypogonadotropic hypogonadism (CHH), a heterogeneous disease characterized by delayed/absent puberty and/or infertility. Although this association is established in humans, murine models failed to fully recapitulate the reproductive and olfactory phenotypes observed in patients harboring PROKR2 mutations. Here, taking advantage of zebrafish model we investigated the role of prokr1b (ortholog of human PROKR2) during early stages of GnRH neuronal migration. Real-Time PCR and whole mount in situ hybridization assays indicate that prokr1b spatial-temporal expression is consistent with gnrh3. Moreover, knockdown and knockout of prokr1b altered the correct development of GnRH3 fibers, a phenotype that is rescued by injection of prokr1b mRNA. These results suggest that prokr1b regulates the development of the GnRH3 system in zebrafish. Analysis of gonads development and mating experiments indicate that prokr1b is not required for fertility in zebrafish, although its loss determine changes also at the testis level. Altogether, our results support the thesis of a divergent evolution in the control of vertebrate reproduction and provide a useful in vivo model for deciphering the mechanisms underlying the effect of PROKR2 allelic variants on CHH.Ivan BassiFrancesca LuzzaniFederica MarelliValeria VezzoliLudovica CotellessaDavid A. ProberLuca PersaniYoav GothilfMarco BonomiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-9 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ivan Bassi Francesca Luzzani Federica Marelli Valeria Vezzoli Ludovica Cotellessa David A. Prober Luca Persani Yoav Gothilf Marco Bonomi Prokineticin receptor 2 affects GnRH3 neuron ontogeny but not fertility in zebrafish
description	Abstract Prokineticin receptors (PROKR1 and PROKR2) are G protein-coupled receptors which control human central and peripheral reproductive processes. Importantly, allelic variants of PROKR2 in humans are associated with altered migration of GnRH neurons, resulting in congenital hypogonadotropic hypogonadism (CHH), a heterogeneous disease characterized by delayed/absent puberty and/or infertility. Although this association is established in humans, murine models failed to fully recapitulate the reproductive and olfactory phenotypes observed in patients harboring PROKR2 mutations. Here, taking advantage of zebrafish model we investigated the role of prokr1b (ortholog of human PROKR2) during early stages of GnRH neuronal migration. Real-Time PCR and whole mount in situ hybridization assays indicate that prokr1b spatial-temporal expression is consistent with gnrh3. Moreover, knockdown and knockout of prokr1b altered the correct development of GnRH3 fibers, a phenotype that is rescued by injection of prokr1b mRNA. These results suggest that prokr1b regulates the development of the GnRH3 system in zebrafish. Analysis of gonads development and mating experiments indicate that prokr1b is not required for fertility in zebrafish, although its loss determine changes also at the testis level. Altogether, our results support the thesis of a divergent evolution in the control of vertebrate reproduction and provide a useful in vivo model for deciphering the mechanisms underlying the effect of PROKR2 allelic variants on CHH.
format	article
author	Ivan Bassi Francesca Luzzani Federica Marelli Valeria Vezzoli Ludovica Cotellessa David A. Prober Luca Persani Yoav Gothilf Marco Bonomi
author_facet	Ivan Bassi Francesca Luzzani Federica Marelli Valeria Vezzoli Ludovica Cotellessa David A. Prober Luca Persani Yoav Gothilf Marco Bonomi
author_sort	Ivan Bassi
title	Prokineticin receptor 2 affects GnRH3 neuron ontogeny but not fertility in zebrafish
title_short	Prokineticin receptor 2 affects GnRH3 neuron ontogeny but not fertility in zebrafish
title_full	Prokineticin receptor 2 affects GnRH3 neuron ontogeny but not fertility in zebrafish
title_fullStr	Prokineticin receptor 2 affects GnRH3 neuron ontogeny but not fertility in zebrafish
title_full_unstemmed	Prokineticin receptor 2 affects GnRH3 neuron ontogeny but not fertility in zebrafish
title_sort	prokineticin receptor 2 affects gnrh3 neuron ontogeny but not fertility in zebrafish
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/a5f5f89f259a47f8945dc2ba1d98ee2d
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Prokineticin receptor 2 affects GnRH3 neuron ontogeny but not fertility in zebrafish

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