Changes in fibroblast growth factor receptors-1c, -2c, -3c, and -4 mRNA in granulosa and theca cells during ovarian follicular growth in dairy cattle

•FGFR1c and FGFR2c mRNA abundance is least in granulosa cells of dominant follicles.•Estradiol decreased FGFR2c mRNA abundance in granulosa cells.•Androgen increased FGFR1c, FGFR2c and FGFR4 mRNA abundance in granulosa cells.•FGFR3c and FGFR4 mRNA abundance in granulosa cells is similar among follic...

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Veröffentlicht in:Domestic animal endocrinology 2022-07, Vol.80, p.106712-106712, Article 106712
Hauptverfasser: Schütz, L.F., Hemple, A.M., Morrell, B.C., Schreiber, N.B., Gilliam, J.N., Cortinovis, C., Totty, M.L., Caloni, F., Aad, P.Y., Spicer, L.J.
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container_title Domestic animal endocrinology
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creator Schütz, L.F.
Hemple, A.M.
Morrell, B.C.
Schreiber, N.B.
Gilliam, J.N.
Cortinovis, C.
Totty, M.L.
Caloni, F.
Aad, P.Y.
Spicer, L.J.
description •FGFR1c and FGFR2c mRNA abundance is least in granulosa cells of dominant follicles.•Estradiol decreased FGFR2c mRNA abundance in granulosa cells.•Androgen increased FGFR1c, FGFR2c and FGFR4 mRNA abundance in granulosa cells.•FGFR3c and FGFR4 mRNA abundance in granulosa cells is similar among follicle types.•FGFR2c and FGFR3c mRNA abundance in theca cells is similar among follicle types. The various fibroblast growth factors (FGF) regulate their function via binding to 4 main FGF receptor (FGFR) subtypes and their splice variants, FGFR1b, FGF1c, FGFR2b, FGFR2c and FGFR3c and FGFR4, but which of these FGFR are expressed in the granulosa (GC) and theca cells (TC), the 2 main cell layers of ovarian follicles, or change during follicular development is unknown. We hypothesized that FGFR1c, FGFR2c and FGFR3c (but not FGFR4) gene expression in GC (but not TC) would change with follicular development. Hence, the objective of this study was to determine if abundance of FGFR1c, FGFR2c, FGFR3c, and FGFR4 mRNA change according to follicular size, steroidogenic status, and days post-ovulation during growth of first-wave dominant follicles in Holstein cattle exhibiting regular estrous cycles. Estrous cycles of non-lactating dairy cattle were synchronized, and ovaries were collected on either d 3 to 4 (n = 8) or d 5 to 6 (n = 8) post-ovulation for GC and TC RNA extraction from small (1–5 mm), medium (5.1 to 8 mm) or large (8.1–18 mm) follicles for real-time PCR analysis. In GC, FGFR1c and FGFR2c mRNA relative abundance was greater in estrogen (E2)-inactive (ie, concentrations of E2 < progesterone, P4) follicles of all sizes than in GC from large E2-active follicles (ie, E2 > P4), whereas FGFR3c and FGFR4 mRNA abundance did not significantly differ among follicle types or days post-estrus. In TC, medium E2-inactive follicles had greater FGFR1c and FGFR4 mRNA abundance than large E2-active and E2–inactive follicles on d 5 to 6 post-ovulation whereas FGFR2c and FGFR3c mRNA abundance did not significantly differ among follicle types or day post-estrus. In vitro experiments revealed that androstenedione increased abundance of FGFR1c, FGFR2c and FGFR4 mRNA in GC whereas estradiol decreased FGFR2c mRNA abundance. Neither androstenedione nor estradiol affected abundance of the various FGFR mRNAs in cultured TC. Taken together, the findings that FGFR1c and FGFR2c mRNA abundance was less in GC of E2-active follicles and FGFR1c and FGFR4 mRNA was greater in TC of medium inactive f
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The various fibroblast growth factors (FGF) regulate their function via binding to 4 main FGF receptor (FGFR) subtypes and their splice variants, FGFR1b, FGF1c, FGFR2b, FGFR2c and FGFR3c and FGFR4, but which of these FGFR are expressed in the granulosa (GC) and theca cells (TC), the 2 main cell layers of ovarian follicles, or change during follicular development is unknown. We hypothesized that FGFR1c, FGFR2c and FGFR3c (but not FGFR4) gene expression in GC (but not TC) would change with follicular development. Hence, the objective of this study was to determine if abundance of FGFR1c, FGFR2c, FGFR3c, and FGFR4 mRNA change according to follicular size, steroidogenic status, and days post-ovulation during growth of first-wave dominant follicles in Holstein cattle exhibiting regular estrous cycles. Estrous cycles of non-lactating dairy cattle were synchronized, and ovaries were collected on either d 3 to 4 (n = 8) or d 5 to 6 (n = 8) post-ovulation for GC and TC RNA extraction from small (1–5 mm), medium (5.1 to 8 mm) or large (8.1–18 mm) follicles for real-time PCR analysis. In GC, FGFR1c and FGFR2c mRNA relative abundance was greater in estrogen (E2)-inactive (ie, concentrations of E2 &lt; progesterone, P4) follicles of all sizes than in GC from large E2-active follicles (ie, E2 &gt; P4), whereas FGFR3c and FGFR4 mRNA abundance did not significantly differ among follicle types or days post-estrus. In TC, medium E2-inactive follicles had greater FGFR1c and FGFR4 mRNA abundance than large E2-active and E2–inactive follicles on d 5 to 6 post-ovulation whereas FGFR2c and FGFR3c mRNA abundance did not significantly differ among follicle types or day post-estrus. In vitro experiments revealed that androstenedione increased abundance of FGFR1c, FGFR2c and FGFR4 mRNA in GC whereas estradiol decreased FGFR2c mRNA abundance. Neither androstenedione nor estradiol affected abundance of the various FGFR mRNAs in cultured TC. Taken together, the findings that FGFR1c and FGFR2c mRNA abundance was less in GC of E2-active follicles and FGFR1c and FGFR4 mRNA was greater in TC of medium inactive follicles at late than at early growing phase of the first dominant follicle support an anti-differentiation role for FGF and their FGFR as well as support the idea that steroid-induced changes in FGF and their receptors may regulate selection of dominant follicles in cattle.</description><identifier>ISSN: 0739-7240</identifier><identifier>EISSN: 1879-0054</identifier><identifier>DOI: 10.1016/j.domaniend.2022.106712</identifier><identifier>PMID: 35276581</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Androstenedione - analysis ; Androstenedione - metabolism ; Animals ; Cattle ; Estradiol - metabolism ; Female ; Fibroblast growth factor receptors (FGFR) ; Follicle growth ; Granulosa cell ; Granulosa Cells - metabolism ; Ovary - metabolism ; Receptor, Fibroblast Growth Factor, Type 2 - genetics ; Receptor, Fibroblast Growth Factor, Type 2 - metabolism ; RNA, Messenger - analysis ; Theca cell ; Theca Cells - metabolism</subject><ispartof>Domestic animal endocrinology, 2022-07, Vol.80, p.106712-106712, Article 106712</ispartof><rights>2022 Elsevier Inc.</rights><rights>Copyright © 2022 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c541t-af213de619268c8ee75c03922284e1d690ccf307b584114dee1c803d55f059aa3</citedby><cites>FETCH-LOGICAL-c541t-af213de619268c8ee75c03922284e1d690ccf307b584114dee1c803d55f059aa3</cites><orcidid>0000-0003-2911-6130</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0739724022000030$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35276581$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Schütz, L.F.</creatorcontrib><creatorcontrib>Hemple, A.M.</creatorcontrib><creatorcontrib>Morrell, B.C.</creatorcontrib><creatorcontrib>Schreiber, N.B.</creatorcontrib><creatorcontrib>Gilliam, J.N.</creatorcontrib><creatorcontrib>Cortinovis, C.</creatorcontrib><creatorcontrib>Totty, M.L.</creatorcontrib><creatorcontrib>Caloni, F.</creatorcontrib><creatorcontrib>Aad, P.Y.</creatorcontrib><creatorcontrib>Spicer, L.J.</creatorcontrib><title>Changes in fibroblast growth factor receptors-1c, -2c, -3c, and -4 mRNA in granulosa and theca cells during ovarian follicular growth in dairy cattle</title><title>Domestic animal endocrinology</title><addtitle>Domest Anim Endocrinol</addtitle><description>•FGFR1c and FGFR2c mRNA abundance is least in granulosa cells of dominant follicles.•Estradiol decreased FGFR2c mRNA abundance in granulosa cells.•Androgen increased FGFR1c, FGFR2c and FGFR4 mRNA abundance in granulosa cells.•FGFR3c and FGFR4 mRNA abundance in granulosa cells is similar among follicle types.•FGFR2c and FGFR3c mRNA abundance in theca cells is similar among follicle types. The various fibroblast growth factors (FGF) regulate their function via binding to 4 main FGF receptor (FGFR) subtypes and their splice variants, FGFR1b, FGF1c, FGFR2b, FGFR2c and FGFR3c and FGFR4, but which of these FGFR are expressed in the granulosa (GC) and theca cells (TC), the 2 main cell layers of ovarian follicles, or change during follicular development is unknown. We hypothesized that FGFR1c, FGFR2c and FGFR3c (but not FGFR4) gene expression in GC (but not TC) would change with follicular development. Hence, the objective of this study was to determine if abundance of FGFR1c, FGFR2c, FGFR3c, and FGFR4 mRNA change according to follicular size, steroidogenic status, and days post-ovulation during growth of first-wave dominant follicles in Holstein cattle exhibiting regular estrous cycles. Estrous cycles of non-lactating dairy cattle were synchronized, and ovaries were collected on either d 3 to 4 (n = 8) or d 5 to 6 (n = 8) post-ovulation for GC and TC RNA extraction from small (1–5 mm), medium (5.1 to 8 mm) or large (8.1–18 mm) follicles for real-time PCR analysis. In GC, FGFR1c and FGFR2c mRNA relative abundance was greater in estrogen (E2)-inactive (ie, concentrations of E2 &lt; progesterone, P4) follicles of all sizes than in GC from large E2-active follicles (ie, E2 &gt; P4), whereas FGFR3c and FGFR4 mRNA abundance did not significantly differ among follicle types or days post-estrus. In TC, medium E2-inactive follicles had greater FGFR1c and FGFR4 mRNA abundance than large E2-active and E2–inactive follicles on d 5 to 6 post-ovulation whereas FGFR2c and FGFR3c mRNA abundance did not significantly differ among follicle types or day post-estrus. In vitro experiments revealed that androstenedione increased abundance of FGFR1c, FGFR2c and FGFR4 mRNA in GC whereas estradiol decreased FGFR2c mRNA abundance. Neither androstenedione nor estradiol affected abundance of the various FGFR mRNAs in cultured TC. Taken together, the findings that FGFR1c and FGFR2c mRNA abundance was less in GC of E2-active follicles and FGFR1c and FGFR4 mRNA was greater in TC of medium inactive follicles at late than at early growing phase of the first dominant follicle support an anti-differentiation role for FGF and their FGFR as well as support the idea that steroid-induced changes in FGF and their receptors may regulate selection of dominant follicles in cattle.</description><subject>Androstenedione - analysis</subject><subject>Androstenedione - metabolism</subject><subject>Animals</subject><subject>Cattle</subject><subject>Estradiol - metabolism</subject><subject>Female</subject><subject>Fibroblast growth factor receptors (FGFR)</subject><subject>Follicle growth</subject><subject>Granulosa cell</subject><subject>Granulosa Cells - metabolism</subject><subject>Ovary - metabolism</subject><subject>Receptor, Fibroblast Growth Factor, Type 2 - genetics</subject><subject>Receptor, Fibroblast Growth Factor, Type 2 - metabolism</subject><subject>RNA, Messenger - analysis</subject><subject>Theca cell</subject><subject>Theca Cells - metabolism</subject><issn>0739-7240</issn><issn>1879-0054</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUUuP0zAQthCILQt_AXzkQIrtPJxckKqKl7QCCcHZmtqT1JUTF9vpan8I_xeH7lZw4jJjeb6Hxx8hrzhbc8abt4e18SNMFiezFkyIfNtILh6RFW9lVzBWV4_JismyK6So2BV5FuOBMSYz-ym5Kmshm7rlK_Jru4dpwEjtRHu7C37nICY6BH-b9rQHnXygATUe8yEWXL-hhVhKmQtMhhYVHb992Sz8IcA0Ox_hzyDtUQPV6FykZg52Gqg_QbCQjbxzVs8OwoNRZhuw4Y5qSMnhc_KkBxfxxX2_Jj8-vP--_VTcfP34ebu5KXRd8VRAL3hpsOGdaFrdIspas7ITQrQVctN0TOu-ZHJXtxXnlUHkumWlqeue1R1AeU3enXWP825Eo3FKAZw6BjtCuFMerPp3Mtm9GvxJdVxUjeyywOt7geB_zhiTGm1cdoYJ_RyVaMpWcllWLEPlGaqDjzFgf7HhTC2hqoO6hKqWUNU51Mx8-fcrL7yHFDNgcwZg_quTxaCizioajc3RpSxr_2vyG_bRuGU</recordid><startdate>20220701</startdate><enddate>20220701</enddate><creator>Schütz, L.F.</creator><creator>Hemple, A.M.</creator><creator>Morrell, B.C.</creator><creator>Schreiber, N.B.</creator><creator>Gilliam, J.N.</creator><creator>Cortinovis, C.</creator><creator>Totty, M.L.</creator><creator>Caloni, F.</creator><creator>Aad, P.Y.</creator><creator>Spicer, L.J.</creator><general>Elsevier Inc</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>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-2911-6130</orcidid></search><sort><creationdate>20220701</creationdate><title>Changes in fibroblast growth factor receptors-1c, -2c, -3c, and -4 mRNA in granulosa and theca cells during ovarian follicular growth in dairy cattle</title><author>Schütz, L.F. ; Hemple, A.M. ; Morrell, B.C. ; Schreiber, N.B. ; Gilliam, J.N. ; Cortinovis, C. ; Totty, M.L. ; Caloni, F. ; Aad, P.Y. ; Spicer, L.J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c541t-af213de619268c8ee75c03922284e1d690ccf307b584114dee1c803d55f059aa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Androstenedione - analysis</topic><topic>Androstenedione - metabolism</topic><topic>Animals</topic><topic>Cattle</topic><topic>Estradiol - metabolism</topic><topic>Female</topic><topic>Fibroblast growth factor receptors (FGFR)</topic><topic>Follicle growth</topic><topic>Granulosa cell</topic><topic>Granulosa Cells - metabolism</topic><topic>Ovary - metabolism</topic><topic>Receptor, Fibroblast Growth Factor, Type 2 - genetics</topic><topic>Receptor, Fibroblast Growth Factor, Type 2 - metabolism</topic><topic>RNA, Messenger - analysis</topic><topic>Theca cell</topic><topic>Theca Cells - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schütz, L.F.</creatorcontrib><creatorcontrib>Hemple, A.M.</creatorcontrib><creatorcontrib>Morrell, B.C.</creatorcontrib><creatorcontrib>Schreiber, N.B.</creatorcontrib><creatorcontrib>Gilliam, J.N.</creatorcontrib><creatorcontrib>Cortinovis, C.</creatorcontrib><creatorcontrib>Totty, M.L.</creatorcontrib><creatorcontrib>Caloni, F.</creatorcontrib><creatorcontrib>Aad, P.Y.</creatorcontrib><creatorcontrib>Spicer, L.J.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Domestic animal endocrinology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Schütz, L.F.</au><au>Hemple, A.M.</au><au>Morrell, B.C.</au><au>Schreiber, N.B.</au><au>Gilliam, J.N.</au><au>Cortinovis, C.</au><au>Totty, M.L.</au><au>Caloni, F.</au><au>Aad, P.Y.</au><au>Spicer, L.J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Changes in fibroblast growth factor receptors-1c, -2c, -3c, and -4 mRNA in granulosa and theca cells during ovarian follicular growth in dairy cattle</atitle><jtitle>Domestic animal endocrinology</jtitle><addtitle>Domest Anim Endocrinol</addtitle><date>2022-07-01</date><risdate>2022</risdate><volume>80</volume><spage>106712</spage><epage>106712</epage><pages>106712-106712</pages><artnum>106712</artnum><issn>0739-7240</issn><eissn>1879-0054</eissn><abstract>•FGFR1c and FGFR2c mRNA abundance is least in granulosa cells of dominant follicles.•Estradiol decreased FGFR2c mRNA abundance in granulosa cells.•Androgen increased FGFR1c, FGFR2c and FGFR4 mRNA abundance in granulosa cells.•FGFR3c and FGFR4 mRNA abundance in granulosa cells is similar among follicle types.•FGFR2c and FGFR3c mRNA abundance in theca cells is similar among follicle types. The various fibroblast growth factors (FGF) regulate their function via binding to 4 main FGF receptor (FGFR) subtypes and their splice variants, FGFR1b, FGF1c, FGFR2b, FGFR2c and FGFR3c and FGFR4, but which of these FGFR are expressed in the granulosa (GC) and theca cells (TC), the 2 main cell layers of ovarian follicles, or change during follicular development is unknown. We hypothesized that FGFR1c, FGFR2c and FGFR3c (but not FGFR4) gene expression in GC (but not TC) would change with follicular development. Hence, the objective of this study was to determine if abundance of FGFR1c, FGFR2c, FGFR3c, and FGFR4 mRNA change according to follicular size, steroidogenic status, and days post-ovulation during growth of first-wave dominant follicles in Holstein cattle exhibiting regular estrous cycles. Estrous cycles of non-lactating dairy cattle were synchronized, and ovaries were collected on either d 3 to 4 (n = 8) or d 5 to 6 (n = 8) post-ovulation for GC and TC RNA extraction from small (1–5 mm), medium (5.1 to 8 mm) or large (8.1–18 mm) follicles for real-time PCR analysis. In GC, FGFR1c and FGFR2c mRNA relative abundance was greater in estrogen (E2)-inactive (ie, concentrations of E2 &lt; progesterone, P4) follicles of all sizes than in GC from large E2-active follicles (ie, E2 &gt; P4), whereas FGFR3c and FGFR4 mRNA abundance did not significantly differ among follicle types or days post-estrus. In TC, medium E2-inactive follicles had greater FGFR1c and FGFR4 mRNA abundance than large E2-active and E2–inactive follicles on d 5 to 6 post-ovulation whereas FGFR2c and FGFR3c mRNA abundance did not significantly differ among follicle types or day post-estrus. In vitro experiments revealed that androstenedione increased abundance of FGFR1c, FGFR2c and FGFR4 mRNA in GC whereas estradiol decreased FGFR2c mRNA abundance. Neither androstenedione nor estradiol affected abundance of the various FGFR mRNAs in cultured TC. Taken together, the findings that FGFR1c and FGFR2c mRNA abundance was less in GC of E2-active follicles and FGFR1c and FGFR4 mRNA was greater in TC of medium inactive follicles at late than at early growing phase of the first dominant follicle support an anti-differentiation role for FGF and their FGFR as well as support the idea that steroid-induced changes in FGF and their receptors may regulate selection of dominant follicles in cattle.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>35276581</pmid><doi>10.1016/j.domaniend.2022.106712</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0003-2911-6130</orcidid><oa>free_for_read</oa></addata></record>
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subjects Androstenedione - analysis
Androstenedione - metabolism
Animals
Cattle
Estradiol - metabolism
Female
Fibroblast growth factor receptors (FGFR)
Follicle growth
Granulosa cell
Granulosa Cells - metabolism
Ovary - metabolism
Receptor, Fibroblast Growth Factor, Type 2 - genetics
Receptor, Fibroblast Growth Factor, Type 2 - metabolism
RNA, Messenger - analysis
Theca cell
Theca Cells - metabolism
title Changes in fibroblast growth factor receptors-1c, -2c, -3c, and -4 mRNA in granulosa and theca cells during ovarian follicular growth in dairy cattle
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