Genetic analysis of activin/inhibin β subunits in zebrafish development and reproduction

Activin and inhibin are both dimeric proteins sharing the same β subunits that belong to the TGF-β superfamily. They are well known for stimulating and inhibiting pituitary FSH secretion, respectively, in mammals. In addition, activin also acts as a mesoderm-inducing factor in frogs. However, their...

Full description

Saved in:
Bibliographic Details
Published in:PLoS genetics 2022-12, Vol.18 (12), p.e1010523-e1010523
Main Authors: Zhao, Cheng, Zhai, Yue, Geng, Ruijing, Wu, Kun, Song, Weiyi, Ai, Nana, Ge, Wei
Format: Article
Language:English
Subjects:
Activin
Activins - genetics
Activins - metabolism
Animals
Aromatase
Biology and Life Sciences
Cell activation
Cell growth
CRISPR
Danio rerio
Developmental biology
Embryos
Fecundity
Female
Females
Fertility
Fibrosis
Follicle-stimulating hormone
Follicles
Folliculogenesis
Genetic analysis
Growth factors
Hatching
Homeostasis
Hypertrophy
Inhibin
Inhibin-beta Subunits - genetics
Inhibin-beta Subunits - metabolism
Inhibins - genetics
Inhibins - metabolism
Luteinizing hormone
Mammals
Mammals - metabolism
Medicine and Health Sciences
Mesoderm
Mutants
Ovaries
Pituitary
Reproduction
Reproduction - genetics
Research and Analysis Methods
Roles
Signal transduction
Spermatogenesis
Tumors
Zebrafish
Zebrafish - genetics
Zebrafish - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c526t-f3aad4407eeb4feb6bd64dede4f43302caa9b11ceedb2d11e8a98afe6dbf49043
cites cdi_FETCH-LOGICAL-c526t-f3aad4407eeb4feb6bd64dede4f43302caa9b11ceedb2d11e8a98afe6dbf49043
container_end_page e1010523
container_issue 12
container_start_page e1010523
container_title PLoS genetics
container_volume 18
creator Zhao, Cheng
Zhai, Yue
Geng, Ruijing
Wu, Kun
Song, Weiyi
Ai, Nana
Ge, Wei
description Activin and inhibin are both dimeric proteins sharing the same β subunits that belong to the TGF-β superfamily. They are well known for stimulating and inhibiting pituitary FSH secretion, respectively, in mammals. In addition, activin also acts as a mesoderm-inducing factor in frogs. However, their functions in development and reproduction of other species are poorly defined. In this study, we disrupted all three activin/inhibin β subunits (βAa, inhbaa; βAb, inhbab; and βB, inhbb) in zebrafish using CRISPR/Cas9. The loss of βAa/b but not βB led to a high mortality rate in the post-hatching stage. Surprisingly, the expression of fshb but not lhb in the pituitary increased in the female βA mutant together with aromatase (cyp19a1a) in the ovary. The single mutant of βAa/b showed normal folliculogenesis in young females; however, their double mutant (inhbaa-/-;inhbab-/-) showed delayed follicle activation, granulosa cell hypertrophy, stromal cell accumulation and tissue fibrosis. The ovary of inhbaa-/- deteriorated progressively after 180 dpf with reduced fecundity and the folliculogenesis ceased completely around 540 dpf. In addition, tumor- or cyst-like tissues started to appear in the inhbaa-/- ovary after about one year. In contrast to females, activin βAa/b mutant males showed normal spermatogenesis and fertility. As for activin βB subunit, the inhbb-/- mutant exhibited normal folliculogenesis, spermatogenesis and fertility in both sexes; however, the fecundity of mutant females decreased dramatically at 270 dpf with accumulation of early follicles. In summary, the activin-inhibin system plays an indispensable role in fish reproduction, in particular folliculogenesis and ovarian homeostasis.
doi_str_mv 10.1371/journal.pgen.1010523
format article
fullrecord <record><control><sourceid>proquest_plos_</sourceid><recordid>TN_cdi_plos_journals_2766098430</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_7a2334fd07f049fa955e134f95a25aeb</doaj_id><sourcerecordid>2766098430</sourcerecordid><originalsourceid>FETCH-LOGICAL-c526t-f3aad4407eeb4feb6bd64dede4f43302caa9b11ceedb2d11e8a98afe6dbf49043</originalsourceid><addsrcrecordid>eNptUsFu1DAQjRCIlsIfIIjEpZfd2rGdxBekqqKlUqVeyoGTNY7Hu15l7WAnK5XP4kP4JrxsWrWIk-3xe2_ejF5RvKdkSVlDzzZhih765bBCv6SEElGxF8UxFYItGk74yyf3o-JNShtCmGhl87o4YjWvpajq4-L7FXocXVdC1rpPLpXBltCNbuf8mfNrp50vf_8q06Qn78ZU5udP1BGsS-vS4A77MGzRj1nAlBGHGMyU6cG_LV5Z6BO-m8-T4tvll7uLr4ub26vri_ObRZcNjAvLAAznpEHU3KKutam5QYPccsZI1QFITWmHaHRlKMUWZAsWa6Mtl4Szk-LjQXfoQ1LzVpKqmromsuWMZMT1AWECbNQQ3RbivQrg1N9CiCsFMe-gR9VAxRi3hjSWcGlBCoE0F6SASgDqrPV57jbpLZouTx6hfyb6_Me7tVqFnZKN4NlQFjidBWL4MWEa1dalDvsePIZp75s3hFSt2Pv-9A_0_9PxA6qLIaWI9tEMJWqflAeW2idFzUnJtA9PB3kkPUSD_QG3HcAs</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2766098430</pqid></control><display><type>article</type><title>Genetic analysis of activin/inhibin β subunits in zebrafish development and reproduction</title><source>Publicly Available Content Database</source><source>PubMed Central</source><creator>Zhao, Cheng ; Zhai, Yue ; Geng, Ruijing ; Wu, Kun ; Song, Weiyi ; Ai, Nana ; Ge, Wei</creator><contributor>Mullins, Mary C.</contributor><creatorcontrib>Zhao, Cheng ; Zhai, Yue ; Geng, Ruijing ; Wu, Kun ; Song, Weiyi ; Ai, Nana ; Ge, Wei ; Mullins, Mary C.</creatorcontrib><description>Activin and inhibin are both dimeric proteins sharing the same β subunits that belong to the TGF-β superfamily. They are well known for stimulating and inhibiting pituitary FSH secretion, respectively, in mammals. In addition, activin also acts as a mesoderm-inducing factor in frogs. However, their functions in development and reproduction of other species are poorly defined. In this study, we disrupted all three activin/inhibin β subunits (βAa, inhbaa; βAb, inhbab; and βB, inhbb) in zebrafish using CRISPR/Cas9. The loss of βAa/b but not βB led to a high mortality rate in the post-hatching stage. Surprisingly, the expression of fshb but not lhb in the pituitary increased in the female βA mutant together with aromatase (cyp19a1a) in the ovary. The single mutant of βAa/b showed normal folliculogenesis in young females; however, their double mutant (inhbaa-/-;inhbab-/-) showed delayed follicle activation, granulosa cell hypertrophy, stromal cell accumulation and tissue fibrosis. The ovary of inhbaa-/- deteriorated progressively after 180 dpf with reduced fecundity and the folliculogenesis ceased completely around 540 dpf. In addition, tumor- or cyst-like tissues started to appear in the inhbaa-/- ovary after about one year. In contrast to females, activin βAa/b mutant males showed normal spermatogenesis and fertility. As for activin βB subunit, the inhbb-/- mutant exhibited normal folliculogenesis, spermatogenesis and fertility in both sexes; however, the fecundity of mutant females decreased dramatically at 270 dpf with accumulation of early follicles. In summary, the activin-inhibin system plays an indispensable role in fish reproduction, in particular folliculogenesis and ovarian homeostasis.</description><identifier>ISSN: 1553-7404</identifier><identifier>ISSN: 1553-7390</identifier><identifier>EISSN: 1553-7404</identifier><identifier>DOI: 10.1371/journal.pgen.1010523</identifier><identifier>PMID: 36469526</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Activin ; Activins - genetics ; Activins - metabolism ; Animals ; Aromatase ; Biology and Life Sciences ; Cell activation ; Cell growth ; CRISPR ; Danio rerio ; Developmental biology ; Embryos ; Fecundity ; Female ; Females ; Fertility ; Fibrosis ; Follicle-stimulating hormone ; Follicles ; Folliculogenesis ; Genetic analysis ; Growth factors ; Hatching ; Homeostasis ; Hypertrophy ; Inhibin ; Inhibin-beta Subunits - genetics ; Inhibin-beta Subunits - metabolism ; Inhibins - genetics ; Inhibins - metabolism ; Luteinizing hormone ; Mammals ; Mammals - metabolism ; Medicine and Health Sciences ; Mesoderm ; Mutants ; Ovaries ; Pituitary ; Reproduction ; Reproduction - genetics ; Research and Analysis Methods ; Roles ; Signal transduction ; Spermatogenesis ; Tumors ; Zebrafish ; Zebrafish - genetics ; Zebrafish - metabolism</subject><ispartof>PLoS genetics, 2022-12, Vol.18 (12), p.e1010523-e1010523</ispartof><rights>Copyright: © 2022 Zhao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</rights><rights>2022 Zhao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2022 Zhao et al 2022 Zhao et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-f3aad4407eeb4feb6bd64dede4f43302caa9b11ceedb2d11e8a98afe6dbf49043</citedby><cites>FETCH-LOGICAL-c526t-f3aad4407eeb4feb6bd64dede4f43302caa9b11ceedb2d11e8a98afe6dbf49043</cites><orcidid>0000-0002-4296-1585</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2766098430/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2766098430?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25751,27922,27923,37010,37011,44588,53789,53791,74896</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36469526$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Mullins, Mary C.</contributor><creatorcontrib>Zhao, Cheng</creatorcontrib><creatorcontrib>Zhai, Yue</creatorcontrib><creatorcontrib>Geng, Ruijing</creatorcontrib><creatorcontrib>Wu, Kun</creatorcontrib><creatorcontrib>Song, Weiyi</creatorcontrib><creatorcontrib>Ai, Nana</creatorcontrib><creatorcontrib>Ge, Wei</creatorcontrib><title>Genetic analysis of activin/inhibin β subunits in zebrafish development and reproduction</title><title>PLoS genetics</title><addtitle>PLoS Genet</addtitle><description>Activin and inhibin are both dimeric proteins sharing the same β subunits that belong to the TGF-β superfamily. They are well known for stimulating and inhibiting pituitary FSH secretion, respectively, in mammals. In addition, activin also acts as a mesoderm-inducing factor in frogs. However, their functions in development and reproduction of other species are poorly defined. In this study, we disrupted all three activin/inhibin β subunits (βAa, inhbaa; βAb, inhbab; and βB, inhbb) in zebrafish using CRISPR/Cas9. The loss of βAa/b but not βB led to a high mortality rate in the post-hatching stage. Surprisingly, the expression of fshb but not lhb in the pituitary increased in the female βA mutant together with aromatase (cyp19a1a) in the ovary. The single mutant of βAa/b showed normal folliculogenesis in young females; however, their double mutant (inhbaa-/-;inhbab-/-) showed delayed follicle activation, granulosa cell hypertrophy, stromal cell accumulation and tissue fibrosis. The ovary of inhbaa-/- deteriorated progressively after 180 dpf with reduced fecundity and the folliculogenesis ceased completely around 540 dpf. In addition, tumor- or cyst-like tissues started to appear in the inhbaa-/- ovary after about one year. In contrast to females, activin βAa/b mutant males showed normal spermatogenesis and fertility. As for activin βB subunit, the inhbb-/- mutant exhibited normal folliculogenesis, spermatogenesis and fertility in both sexes; however, the fecundity of mutant females decreased dramatically at 270 dpf with accumulation of early follicles. In summary, the activin-inhibin system plays an indispensable role in fish reproduction, in particular folliculogenesis and ovarian homeostasis.</description><subject>Activin</subject><subject>Activins - genetics</subject><subject>Activins - metabolism</subject><subject>Animals</subject><subject>Aromatase</subject><subject>Biology and Life Sciences</subject><subject>Cell activation</subject><subject>Cell growth</subject><subject>CRISPR</subject><subject>Danio rerio</subject><subject>Developmental biology</subject><subject>Embryos</subject><subject>Fecundity</subject><subject>Female</subject><subject>Females</subject><subject>Fertility</subject><subject>Fibrosis</subject><subject>Follicle-stimulating hormone</subject><subject>Follicles</subject><subject>Folliculogenesis</subject><subject>Genetic analysis</subject><subject>Growth factors</subject><subject>Hatching</subject><subject>Homeostasis</subject><subject>Hypertrophy</subject><subject>Inhibin</subject><subject>Inhibin-beta Subunits - genetics</subject><subject>Inhibin-beta Subunits - metabolism</subject><subject>Inhibins - genetics</subject><subject>Inhibins - metabolism</subject><subject>Luteinizing hormone</subject><subject>Mammals</subject><subject>Mammals - metabolism</subject><subject>Medicine and Health Sciences</subject><subject>Mesoderm</subject><subject>Mutants</subject><subject>Ovaries</subject><subject>Pituitary</subject><subject>Reproduction</subject><subject>Reproduction - genetics</subject><subject>Research and Analysis Methods</subject><subject>Roles</subject><subject>Signal transduction</subject><subject>Spermatogenesis</subject><subject>Tumors</subject><subject>Zebrafish</subject><subject>Zebrafish - genetics</subject><subject>Zebrafish - metabolism</subject><issn>1553-7404</issn><issn>1553-7390</issn><issn>1553-7404</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNptUsFu1DAQjRCIlsIfIIjEpZfd2rGdxBekqqKlUqVeyoGTNY7Hu15l7WAnK5XP4kP4JrxsWrWIk-3xe2_ejF5RvKdkSVlDzzZhih765bBCv6SEElGxF8UxFYItGk74yyf3o-JNShtCmGhl87o4YjWvpajq4-L7FXocXVdC1rpPLpXBltCNbuf8mfNrp50vf_8q06Qn78ZU5udP1BGsS-vS4A77MGzRj1nAlBGHGMyU6cG_LV5Z6BO-m8-T4tvll7uLr4ub26vri_ObRZcNjAvLAAznpEHU3KKutam5QYPccsZI1QFITWmHaHRlKMUWZAsWa6Mtl4Szk-LjQXfoQ1LzVpKqmromsuWMZMT1AWECbNQQ3RbivQrg1N9CiCsFMe-gR9VAxRi3hjSWcGlBCoE0F6SASgDqrPV57jbpLZouTx6hfyb6_Me7tVqFnZKN4NlQFjidBWL4MWEa1dalDvsePIZp75s3hFSt2Pv-9A_0_9PxA6qLIaWI9tEMJWqflAeW2idFzUnJtA9PB3kkPUSD_QG3HcAs</recordid><startdate>20221201</startdate><enddate>20221201</enddate><creator>Zhao, Cheng</creator><creator>Zhai, Yue</creator><creator>Geng, Ruijing</creator><creator>Wu, Kun</creator><creator>Song, Weiyi</creator><creator>Ai, Nana</creator><creator>Ge, Wei</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</scope><scope>7QR</scope><scope>7SS</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-4296-1585</orcidid></search><sort><creationdate>20221201</creationdate><title>Genetic analysis of activin/inhibin β subunits in zebrafish development and reproduction</title><author>Zhao, Cheng ; Zhai, Yue ; Geng, Ruijing ; Wu, Kun ; Song, Weiyi ; Ai, Nana ; Ge, Wei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-f3aad4407eeb4feb6bd64dede4f43302caa9b11ceedb2d11e8a98afe6dbf49043</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Activin</topic><topic>Activins - genetics</topic><topic>Activins - metabolism</topic><topic>Animals</topic><topic>Aromatase</topic><topic>Biology and Life Sciences</topic><topic>Cell activation</topic><topic>Cell growth</topic><topic>CRISPR</topic><topic>Danio rerio</topic><topic>Developmental biology</topic><topic>Embryos</topic><topic>Fecundity</topic><topic>Female</topic><topic>Females</topic><topic>Fertility</topic><topic>Fibrosis</topic><topic>Follicle-stimulating hormone</topic><topic>Follicles</topic><topic>Folliculogenesis</topic><topic>Genetic analysis</topic><topic>Growth factors</topic><topic>Hatching</topic><topic>Homeostasis</topic><topic>Hypertrophy</topic><topic>Inhibin</topic><topic>Inhibin-beta Subunits - genetics</topic><topic>Inhibin-beta Subunits - metabolism</topic><topic>Inhibins - genetics</topic><topic>Inhibins - metabolism</topic><topic>Luteinizing hormone</topic><topic>Mammals</topic><topic>Mammals - metabolism</topic><topic>Medicine and Health Sciences</topic><topic>Mesoderm</topic><topic>Mutants</topic><topic>Ovaries</topic><topic>Pituitary</topic><topic>Reproduction</topic><topic>Reproduction - genetics</topic><topic>Research and Analysis Methods</topic><topic>Roles</topic><topic>Signal transduction</topic><topic>Spermatogenesis</topic><topic>Tumors</topic><topic>Zebrafish</topic><topic>Zebrafish - genetics</topic><topic>Zebrafish - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhao, Cheng</creatorcontrib><creatorcontrib>Zhai, Yue</creatorcontrib><creatorcontrib>Geng, Ruijing</creatorcontrib><creatorcontrib>Wu, Kun</creatorcontrib><creatorcontrib>Song, Weiyi</creatorcontrib><creatorcontrib>Ai, Nana</creatorcontrib><creatorcontrib>Ge, Wei</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium &amp; Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>PHMC-Proquest健康医学期刊库</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Biological Sciences</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals</collection><jtitle>PLoS genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhao, Cheng</au><au>Zhai, Yue</au><au>Geng, Ruijing</au><au>Wu, Kun</au><au>Song, Weiyi</au><au>Ai, Nana</au><au>Ge, Wei</au><au>Mullins, Mary C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic analysis of activin/inhibin β subunits in zebrafish development and reproduction</atitle><jtitle>PLoS genetics</jtitle><addtitle>PLoS Genet</addtitle><date>2022-12-01</date><risdate>2022</risdate><volume>18</volume><issue>12</issue><spage>e1010523</spage><epage>e1010523</epage><pages>e1010523-e1010523</pages><issn>1553-7404</issn><issn>1553-7390</issn><eissn>1553-7404</eissn><abstract>Activin and inhibin are both dimeric proteins sharing the same β subunits that belong to the TGF-β superfamily. They are well known for stimulating and inhibiting pituitary FSH secretion, respectively, in mammals. In addition, activin also acts as a mesoderm-inducing factor in frogs. However, their functions in development and reproduction of other species are poorly defined. In this study, we disrupted all three activin/inhibin β subunits (βAa, inhbaa; βAb, inhbab; and βB, inhbb) in zebrafish using CRISPR/Cas9. The loss of βAa/b but not βB led to a high mortality rate in the post-hatching stage. Surprisingly, the expression of fshb but not lhb in the pituitary increased in the female βA mutant together with aromatase (cyp19a1a) in the ovary. The single mutant of βAa/b showed normal folliculogenesis in young females; however, their double mutant (inhbaa-/-;inhbab-/-) showed delayed follicle activation, granulosa cell hypertrophy, stromal cell accumulation and tissue fibrosis. The ovary of inhbaa-/- deteriorated progressively after 180 dpf with reduced fecundity and the folliculogenesis ceased completely around 540 dpf. In addition, tumor- or cyst-like tissues started to appear in the inhbaa-/- ovary after about one year. In contrast to females, activin βAa/b mutant males showed normal spermatogenesis and fertility. As for activin βB subunit, the inhbb-/- mutant exhibited normal folliculogenesis, spermatogenesis and fertility in both sexes; however, the fecundity of mutant females decreased dramatically at 270 dpf with accumulation of early follicles. In summary, the activin-inhibin system plays an indispensable role in fish reproduction, in particular folliculogenesis and ovarian homeostasis.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>36469526</pmid><doi>10.1371/journal.pgen.1010523</doi><orcidid>https://orcid.org/0000-0002-4296-1585</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1553-7404
ispartof PLoS genetics, 2022-12, Vol.18 (12), p.e1010523-e1010523
issn 1553-7404
1553-7390
1553-7404
language eng
recordid cdi_plos_journals_2766098430
source Publicly Available Content Database; PubMed Central
subjects Activin
Activins - genetics
Activins - metabolism
Animals
Aromatase
Biology and Life Sciences
Cell activation
Cell growth
CRISPR
Danio rerio
Developmental biology
Embryos
Fecundity
Female
Females
Fertility
Fibrosis
Follicle-stimulating hormone
Follicles
Folliculogenesis
Genetic analysis
Growth factors
Hatching
Homeostasis
Hypertrophy
Inhibin
Inhibin-beta Subunits - genetics
Inhibin-beta Subunits - metabolism
Inhibins - genetics
Inhibins - metabolism
Luteinizing hormone
Mammals
Mammals - metabolism
Medicine and Health Sciences
Mesoderm
Mutants
Ovaries
Pituitary
Reproduction
Reproduction - genetics
Research and Analysis Methods
Roles
Signal transduction
Spermatogenesis
Tumors
Zebrafish
Zebrafish - genetics
Zebrafish - metabolism
title Genetic analysis of activin/inhibin β subunits in zebrafish development and reproduction
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-14T13%3A40%3A44IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Genetic%20analysis%20of%20activin/inhibin%20%CE%B2%20subunits%20in%20zebrafish%20development%20and%20reproduction&rft.jtitle=PLoS%20genetics&rft.au=Zhao,%20Cheng&rft.date=2022-12-01&rft.volume=18&rft.issue=12&rft.spage=e1010523&rft.epage=e1010523&rft.pages=e1010523-e1010523&rft.issn=1553-7404&rft.eissn=1553-7404&rft_id=info:doi/10.1371/journal.pgen.1010523&rft_dat=%3Cproquest_plos_%3E2766098430%3C/proquest_plos_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c526t-f3aad4407eeb4feb6bd64dede4f43302caa9b11ceedb2d11e8a98afe6dbf49043%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2766098430&rft_id=info:pmid/36469526&rfr_iscdi=true