Virpi Töhönen, Per Antonson, Nageswara Rao Boggavarapu, Heba Ali, Leticia Apolinario Motaholi, Jan-Åke Gustafsson, Mukesh Varshney, Kenny A Rodriguez-Wallberg, Shintaro Katayama, Ivan Nalvarte, Jose Inzunza
{"title":"Transcriptomic profiling of the oocyte-cumulus-granulosa cell complex from estrogen receptor β knockout mice.","authors":"Virpi Töhönen, Per Antonson, Nageswara Rao Boggavarapu, Heba Ali, Leticia Apolinario Motaholi, Jan-Åke Gustafsson, Mukesh Varshney, Kenny A Rodriguez-Wallberg, Shintaro Katayama, Ivan Nalvarte, Jose Inzunza","doi":"10.1016/j.xfss.2024.08.004","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>To study the role of estrogen receptor β in follicle development and maturation and the response to gonadotropin stimulation aiming at superovulation.</p><p><strong>Design: </strong>Experimental study and transcriptomic analysis.</p><p><strong>Setting: </strong>Karolinka Institutet, medical university.</p><p><strong>Animal(s): </strong>Healthy wild-type (WT) and estrogen receptor β knockout (Esr2-KO) female mice undergoing superovulation at 4 weeks, 7 weeks, and 6 months of age.</p><p><strong>Intervention(s): </strong>Not applicable.</p><p><strong>Main outcome measure(s): </strong>Oocyte yield after superovulation, transcriptomic profiling of cumulus-granulosa cell complexes and oocytes, and immunohistochemical analyses.</p><p><strong>Result(s): </strong>Superovulation of estrogen receptor β (ERβ) knockout mice resulted in reduced oocyte yield at 6 months of age compared with WT mice, but younger mice had similar yields. RNA-seq analysis of cumulus cells from superovulated WT and Esr2-KO mice identified genes and pathways associated with among others adhesion, proliferation, Wnt-signaling, and placed ERβ in bipotential granulosa cell cluster. Loss of ERβ increased expression of the other estrogen receptors Esr1 and Gper1.</p><p><strong>Conclusion(s): </strong>Our results show that ERβ has an important role in regulating ovulation in response to exogenous gonadotropins in 6-month-old mice, but not in younger mice. Our transcriptomic and immunohistochemical observations suggest a dysregulation of the granulosa cell communication and lack of tight coordination between granulosa cell replication and antrum expansion. A significant upregulation of other estrogen receptors may support a compensatory mechanism sustaining fertility during younger age in Esr2-KO mice.</p>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"F&S science","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.xfss.2024.08.004","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Objective: To study the role of estrogen receptor β in follicle development and maturation and the response to gonadotropin stimulation aiming at superovulation.
Design: Experimental study and transcriptomic analysis.
Setting: Karolinka Institutet, medical university.
Animal(s): Healthy wild-type (WT) and estrogen receptor β knockout (Esr2-KO) female mice undergoing superovulation at 4 weeks, 7 weeks, and 6 months of age.
Intervention(s): Not applicable.
Main outcome measure(s): Oocyte yield after superovulation, transcriptomic profiling of cumulus-granulosa cell complexes and oocytes, and immunohistochemical analyses.
Result(s): Superovulation of estrogen receptor β (ERβ) knockout mice resulted in reduced oocyte yield at 6 months of age compared with WT mice, but younger mice had similar yields. RNA-seq analysis of cumulus cells from superovulated WT and Esr2-KO mice identified genes and pathways associated with among others adhesion, proliferation, Wnt-signaling, and placed ERβ in bipotential granulosa cell cluster. Loss of ERβ increased expression of the other estrogen receptors Esr1 and Gper1.
Conclusion(s): Our results show that ERβ has an important role in regulating ovulation in response to exogenous gonadotropins in 6-month-old mice, but not in younger mice. Our transcriptomic and immunohistochemical observations suggest a dysregulation of the granulosa cell communication and lack of tight coordination between granulosa cell replication and antrum expansion. A significant upregulation of other estrogen receptors may support a compensatory mechanism sustaining fertility during younger age in Esr2-KO mice.