Gnrh3 Regulates PGC Proliferation and Sex Differentiation in Developing Zebrafish
Abstract Gonadotropin-releasing hormone (Gnrh) plays important roles in reproduction by stimulating luteinizing hormone release, and subsequently ovulation and sperm release, ultimately controlling reproduction in many species. Here we report on a new role for this decapeptide. Surprisingly, Gnrh3-n...
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| Veröffentlicht in: | Endocrinology (Philadelphia) 2020-01, Vol.161 (1), p.1 |
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| creator | Feng, Ke Cui, Xuefan Song, Yanlong Tao, Binbin Chen, Ji Wang, Jing Liu, Shaojun Sun, Yonghua Zhu, Zuoyan Trudeau, Vance L Hu, Wei |
| description | Abstract
Gonadotropin-releasing hormone (Gnrh) plays important roles in reproduction by stimulating luteinizing hormone release, and subsequently ovulation and sperm release, ultimately controlling reproduction in many species. Here we report on a new role for this decapeptide. Surprisingly, Gnrh3-null zebrafish generated by CRISPR/Cas9 exhibited a male-biased sex ratio. After the dome stage, the number of primordial germ cells (PGCs) in gnrh3-/- fish was lower than that in wild-type, an effect that was partially rescued by gnrh3 overexpression. A terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) analysis revealed no detectable apoptosis of PGCs in gnrh3-/- embryos. Proliferating PGCs could be detected in wild-type embryos, while there was no detectable signal in gnrh3-/- embryos. Compared with wild type, the phosphorylation of AKT was not significantly different in gnrh3-/- embryos, but the phosphorylation of ERK1/2 decreased significantly. Treatment with a Gnrh analog (Alarelin) induced ERK1/2 phosphorylation and increased PGC numbers in both wild-type and gnrh3-/- embryos, and this was blocked by the MEK inhibitor PD0325901. The relative expression of sox9a, amh, and cyp11b were significantly upregulated, while cyp19a1a was significantly downregulated at 18 days post-fertilization in gnrh3-/- zebrafish. Taken together, these results indicate that Gnrh3 plays an important role in early sex differentiation by regulating the proliferation of PGCs through a MAPK-dependent path. |
| doi_str_mv | 10.1210/endocr/bqz024 |
| format | Article |
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Gonadotropin-releasing hormone (Gnrh) plays important roles in reproduction by stimulating luteinizing hormone release, and subsequently ovulation and sperm release, ultimately controlling reproduction in many species. Here we report on a new role for this decapeptide. Surprisingly, Gnrh3-null zebrafish generated by CRISPR/Cas9 exhibited a male-biased sex ratio. After the dome stage, the number of primordial germ cells (PGCs) in gnrh3-/- fish was lower than that in wild-type, an effect that was partially rescued by gnrh3 overexpression. A terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) analysis revealed no detectable apoptosis of PGCs in gnrh3-/- embryos. Proliferating PGCs could be detected in wild-type embryos, while there was no detectable signal in gnrh3-/- embryos. Compared with wild type, the phosphorylation of AKT was not significantly different in gnrh3-/- embryos, but the phosphorylation of ERK1/2 decreased significantly. Treatment with a Gnrh analog (Alarelin) induced ERK1/2 phosphorylation and increased PGC numbers in both wild-type and gnrh3-/- embryos, and this was blocked by the MEK inhibitor PD0325901. The relative expression of sox9a, amh, and cyp11b were significantly upregulated, while cyp19a1a was significantly downregulated at 18 days post-fertilization in gnrh3-/- zebrafish. Taken together, these results indicate that Gnrh3 plays an important role in early sex differentiation by regulating the proliferation of PGCs through a MAPK-dependent path.</description><identifier>ISSN: 0013-7227</identifier><identifier>EISSN: 1945-7170</identifier><identifier>DOI: 10.1210/endocr/bqz024</identifier><identifier>PMID: 31758175</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>AKT protein ; Apoptosis ; CRISPR ; Danio rerio ; Differentiation ; DNA nucleotidylexotransferase ; Embryonic development ; Embryos ; Endocrinology ; Fertilization ; Genetic aspects ; Germ cells ; Gonadotropin releasing hormone ; Gonadotropins ; Hormone release ; Kinases ; Luteinizing hormone ; MAP kinase ; MEK inhibitors ; Ovulation ; Phosphorylation ; Physiological aspects ; Pituitary (anterior) ; Reproduction ; Reproduction (biology) ; Sex ; Sex differentiation ; Sex ratio ; Zebrafish</subject><ispartof>Endocrinology (Philadelphia), 2020-01, Vol.161 (1), p.1</ispartof><rights>Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com 2019</rights><rights>Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.</rights><rights>COPYRIGHT 2020 Oxford University Press</rights><rights>Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c487t-2983a1990c51b24a5031855330f0290417f5542fc0805c8f5c00f4c459959b243</citedby><cites>FETCH-LOGICAL-c487t-2983a1990c51b24a5031855330f0290417f5542fc0805c8f5c00f4c459959b243</cites><orcidid>0000-0002-6475-6427</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31758175$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Feng, Ke</creatorcontrib><creatorcontrib>Cui, Xuefan</creatorcontrib><creatorcontrib>Song, Yanlong</creatorcontrib><creatorcontrib>Tao, Binbin</creatorcontrib><creatorcontrib>Chen, Ji</creatorcontrib><creatorcontrib>Wang, Jing</creatorcontrib><creatorcontrib>Liu, Shaojun</creatorcontrib><creatorcontrib>Sun, Yonghua</creatorcontrib><creatorcontrib>Zhu, Zuoyan</creatorcontrib><creatorcontrib>Trudeau, Vance L</creatorcontrib><creatorcontrib>Hu, Wei</creatorcontrib><title>Gnrh3 Regulates PGC Proliferation and Sex Differentiation in Developing Zebrafish</title><title>Endocrinology (Philadelphia)</title><addtitle>Endocrinology</addtitle><description>Abstract
Gonadotropin-releasing hormone (Gnrh) plays important roles in reproduction by stimulating luteinizing hormone release, and subsequently ovulation and sperm release, ultimately controlling reproduction in many species. Here we report on a new role for this decapeptide. Surprisingly, Gnrh3-null zebrafish generated by CRISPR/Cas9 exhibited a male-biased sex ratio. After the dome stage, the number of primordial germ cells (PGCs) in gnrh3-/- fish was lower than that in wild-type, an effect that was partially rescued by gnrh3 overexpression. A terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) analysis revealed no detectable apoptosis of PGCs in gnrh3-/- embryos. Proliferating PGCs could be detected in wild-type embryos, while there was no detectable signal in gnrh3-/- embryos. Compared with wild type, the phosphorylation of AKT was not significantly different in gnrh3-/- embryos, but the phosphorylation of ERK1/2 decreased significantly. Treatment with a Gnrh analog (Alarelin) induced ERK1/2 phosphorylation and increased PGC numbers in both wild-type and gnrh3-/- embryos, and this was blocked by the MEK inhibitor PD0325901. The relative expression of sox9a, amh, and cyp11b were significantly upregulated, while cyp19a1a was significantly downregulated at 18 days post-fertilization in gnrh3-/- zebrafish. Taken together, these results indicate that Gnrh3 plays an important role in early sex differentiation by regulating the proliferation of PGCs through a MAPK-dependent path.</description><subject>AKT protein</subject><subject>Apoptosis</subject><subject>CRISPR</subject><subject>Danio rerio</subject><subject>Differentiation</subject><subject>DNA nucleotidylexotransferase</subject><subject>Embryonic development</subject><subject>Embryos</subject><subject>Endocrinology</subject><subject>Fertilization</subject><subject>Genetic aspects</subject><subject>Germ cells</subject><subject>Gonadotropin releasing hormone</subject><subject>Gonadotropins</subject><subject>Hormone release</subject><subject>Kinases</subject><subject>Luteinizing hormone</subject><subject>MAP kinase</subject><subject>MEK inhibitors</subject><subject>Ovulation</subject><subject>Phosphorylation</subject><subject>Physiological aspects</subject><subject>Pituitary (anterior)</subject><subject>Reproduction</subject><subject>Reproduction (biology)</subject><subject>Sex</subject><subject>Sex differentiation</subject><subject>Sex ratio</subject><subject>Zebrafish</subject><issn>0013-7227</issn><issn>1945-7170</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNqFkMtLAzEQxoMoWqtHr7Lgxcvq5OVujlK1CgXr6-IlpGlSI9ukJrui_vVG1sfRwzDMx2_mYz6E9jAcYYLh2Ph50PF49vIBhK2hARaMlxWuYB0NADAtK0KqLbSd0nMeGWN0E21RXPE61wDdjH18osWtWXSNak0qpuNRMY2hcdZE1brgC-XnxZ15K86czZrxret154sz82qasHJ-UTyaWVTWpacdtGFVk8zudx-ih4vz-9FlObkeX41OJ6VmddWWRNRUYSFAczwjTHGguOacUrBABDBcWc4ZsRpq4Lq2XANYphkXgou8QIfooL-7iuGlM6mVz6GLPltKwoCx_DuQP2qhGiOdt6GNSi9d0vL0hAl8AjybDlHZUzqGlKKxchXdUsV3iUF-xSz7mGUfc-b3v7272dLMf-mfXDNw2AOhW_1z6xMCe4SP</recordid><startdate>20200101</startdate><enddate>20200101</enddate><creator>Feng, Ke</creator><creator>Cui, Xuefan</creator><creator>Song, Yanlong</creator><creator>Tao, Binbin</creator><creator>Chen, Ji</creator><creator>Wang, Jing</creator><creator>Liu, Shaojun</creator><creator>Sun, Yonghua</creator><creator>Zhu, Zuoyan</creator><creator>Trudeau, Vance L</creator><creator>Hu, Wei</creator><general>Oxford University Press</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><orcidid>https://orcid.org/0000-0002-6475-6427</orcidid></search><sort><creationdate>20200101</creationdate><title>Gnrh3 Regulates PGC Proliferation and Sex Differentiation in Developing Zebrafish</title><author>Feng, Ke ; Cui, Xuefan ; Song, Yanlong ; Tao, Binbin ; Chen, Ji ; Wang, Jing ; Liu, Shaojun ; Sun, Yonghua ; Zhu, Zuoyan ; Trudeau, Vance L ; Hu, Wei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c487t-2983a1990c51b24a5031855330f0290417f5542fc0805c8f5c00f4c459959b243</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>AKT protein</topic><topic>Apoptosis</topic><topic>CRISPR</topic><topic>Danio rerio</topic><topic>Differentiation</topic><topic>DNA nucleotidylexotransferase</topic><topic>Embryonic development</topic><topic>Embryos</topic><topic>Endocrinology</topic><topic>Fertilization</topic><topic>Genetic aspects</topic><topic>Germ cells</topic><topic>Gonadotropin releasing hormone</topic><topic>Gonadotropins</topic><topic>Hormone release</topic><topic>Kinases</topic><topic>Luteinizing hormone</topic><topic>MAP kinase</topic><topic>MEK inhibitors</topic><topic>Ovulation</topic><topic>Phosphorylation</topic><topic>Physiological aspects</topic><topic>Pituitary (anterior)</topic><topic>Reproduction</topic><topic>Reproduction (biology)</topic><topic>Sex</topic><topic>Sex differentiation</topic><topic>Sex ratio</topic><topic>Zebrafish</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Feng, Ke</creatorcontrib><creatorcontrib>Cui, Xuefan</creatorcontrib><creatorcontrib>Song, Yanlong</creatorcontrib><creatorcontrib>Tao, Binbin</creatorcontrib><creatorcontrib>Chen, Ji</creatorcontrib><creatorcontrib>Wang, Jing</creatorcontrib><creatorcontrib>Liu, Shaojun</creatorcontrib><creatorcontrib>Sun, Yonghua</creatorcontrib><creatorcontrib>Zhu, Zuoyan</creatorcontrib><creatorcontrib>Trudeau, Vance L</creatorcontrib><creatorcontrib>Hu, Wei</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Endocrinology (Philadelphia)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Feng, Ke</au><au>Cui, Xuefan</au><au>Song, Yanlong</au><au>Tao, Binbin</au><au>Chen, Ji</au><au>Wang, Jing</au><au>Liu, Shaojun</au><au>Sun, Yonghua</au><au>Zhu, Zuoyan</au><au>Trudeau, Vance L</au><au>Hu, Wei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Gnrh3 Regulates PGC Proliferation and Sex Differentiation in Developing Zebrafish</atitle><jtitle>Endocrinology (Philadelphia)</jtitle><addtitle>Endocrinology</addtitle><date>2020-01-01</date><risdate>2020</risdate><volume>161</volume><issue>1</issue><spage>1</spage><pages>1-</pages><issn>0013-7227</issn><eissn>1945-7170</eissn><abstract>Abstract
Gonadotropin-releasing hormone (Gnrh) plays important roles in reproduction by stimulating luteinizing hormone release, and subsequently ovulation and sperm release, ultimately controlling reproduction in many species. Here we report on a new role for this decapeptide. Surprisingly, Gnrh3-null zebrafish generated by CRISPR/Cas9 exhibited a male-biased sex ratio. After the dome stage, the number of primordial germ cells (PGCs) in gnrh3-/- fish was lower than that in wild-type, an effect that was partially rescued by gnrh3 overexpression. A terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) analysis revealed no detectable apoptosis of PGCs in gnrh3-/- embryos. Proliferating PGCs could be detected in wild-type embryos, while there was no detectable signal in gnrh3-/- embryos. Compared with wild type, the phosphorylation of AKT was not significantly different in gnrh3-/- embryos, but the phosphorylation of ERK1/2 decreased significantly. Treatment with a Gnrh analog (Alarelin) induced ERK1/2 phosphorylation and increased PGC numbers in both wild-type and gnrh3-/- embryos, and this was blocked by the MEK inhibitor PD0325901. The relative expression of sox9a, amh, and cyp11b were significantly upregulated, while cyp19a1a was significantly downregulated at 18 days post-fertilization in gnrh3-/- zebrafish. Taken together, these results indicate that Gnrh3 plays an important role in early sex differentiation by regulating the proliferation of PGCs through a MAPK-dependent path.</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>31758175</pmid><doi>10.1210/endocr/bqz024</doi><orcidid>https://orcid.org/0000-0002-6475-6427</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | AKT protein Apoptosis CRISPR Danio rerio Differentiation DNA nucleotidylexotransferase Embryonic development Embryos Endocrinology Fertilization Genetic aspects Germ cells Gonadotropin releasing hormone Gonadotropins Hormone release Kinases Luteinizing hormone MAP kinase MEK inhibitors Ovulation Phosphorylation Physiological aspects Pituitary (anterior) Reproduction Reproduction (biology) Sex Sex differentiation Sex ratio Zebrafish |
| title | Gnrh3 Regulates PGC Proliferation and Sex Differentiation in Developing Zebrafish |
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