File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: An Embryonic and Induced Pluripotent Stem Cell Model for Ovarian Granulosa Cell Development and Steroidogenesis

TitleAn Embryonic and Induced Pluripotent Stem Cell Model for Ovarian Granulosa Cell Development and Steroidogenesis
Authors
Keywordssteroidogenesis
iPSC
embryonic stem cells
native hormones
ovarian tissue regeneration
Issue Date2018
Citation
Reproductive Sciences, 2018, v. 25, n. 5, p. 712-726 How to Cite?
Abstract© 2017, © The Author(s) 2017. Embryoid bodies (EBs) can serve as a system for evaluating pluripotency, cellular differentiation, and tissue morphogenesis. In this study, we use EBs derived from mouse embryonic stem cells (mESCs) and human amniocyte–derived induced pluripotent stem cells (hAdiPSCs) as a model for ovarian granulosa cell (GC) development and steroidogenic cell commitment. We demonstrated that spontaneously differentiated murine EBs (mEBs) and human EBs (hEBs) displayed ovarian GC markers, such as aromatase (CYP19A1), FOXL2, AMHR2, FSHR, and GJA1. Comparative microarray analysis identified both shared and unique gene expression between mEBs and the maturing mouse ovary. Gene sets related to gonadogenesis, lipid metabolism, and ovarian development were significantly overrepresented in EBs. Of the 29 genes, 15 that were differentially regulated in steroidogenic mEBs displayed temporal expression changes between embryonic, postnatal, and mature ovarian tissues by polymerase chain reaction. Importantly, both mEBs and hEBs were capable of gonadotropin-responsive estradiol (E2) synthesis in vitro (217-759 pg/mL). Live fluorescence-activated cell sorting–sorted AMHR2+granulosa-like cells from mEBs continued to produce E2 after purification (15.3 pg/mL) and secreted significantly more E2 than AMHR2−cells (8.6 pg/mL, P <.05). We conclude that spontaneously differentiated EBs of both mESC and hAdiPSC origin can serve as a biologically relevant model for ovarian GC differentiation and steroidogenic cell commitment. These cells should be further investigated for therapeutic uses, such as stem cell–based hormone replacement therapy and in vitro maturation of oocytes.
Persistent Identifierhttp://hdl.handle.net/10722/262790
ISSN
2023 Impact Factor: 2.6
2023 SCImago Journal Rankings: 0.836
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLipskind, Shane-
dc.contributor.authorLindsey, Jennifer S.-
dc.contributor.authorGerami-Naini, Behzad-
dc.contributor.authorEaton, Jennifer L.-
dc.contributor.authorO’Connell, Daniel-
dc.contributor.authorKiezun, Adam-
dc.contributor.authorHo, Joshua W.K.-
dc.contributor.authorNg, Nicholas-
dc.contributor.authorParasar, Parveen-
dc.contributor.authorNg, Michelle-
dc.contributor.authorNickerson, Michael-
dc.contributor.authorDemirci, Utkan-
dc.contributor.authorMaas, Richard-
dc.contributor.authorAnchan, Raymond M.-
dc.date.accessioned2018-10-08T02:47:03Z-
dc.date.available2018-10-08T02:47:03Z-
dc.date.issued2018-
dc.identifier.citationReproductive Sciences, 2018, v. 25, n. 5, p. 712-726-
dc.identifier.issn1933-7191-
dc.identifier.urihttp://hdl.handle.net/10722/262790-
dc.description.abstract© 2017, © The Author(s) 2017. Embryoid bodies (EBs) can serve as a system for evaluating pluripotency, cellular differentiation, and tissue morphogenesis. In this study, we use EBs derived from mouse embryonic stem cells (mESCs) and human amniocyte–derived induced pluripotent stem cells (hAdiPSCs) as a model for ovarian granulosa cell (GC) development and steroidogenic cell commitment. We demonstrated that spontaneously differentiated murine EBs (mEBs) and human EBs (hEBs) displayed ovarian GC markers, such as aromatase (CYP19A1), FOXL2, AMHR2, FSHR, and GJA1. Comparative microarray analysis identified both shared and unique gene expression between mEBs and the maturing mouse ovary. Gene sets related to gonadogenesis, lipid metabolism, and ovarian development were significantly overrepresented in EBs. Of the 29 genes, 15 that were differentially regulated in steroidogenic mEBs displayed temporal expression changes between embryonic, postnatal, and mature ovarian tissues by polymerase chain reaction. Importantly, both mEBs and hEBs were capable of gonadotropin-responsive estradiol (E2) synthesis in vitro (217-759 pg/mL). Live fluorescence-activated cell sorting–sorted AMHR2+granulosa-like cells from mEBs continued to produce E2 after purification (15.3 pg/mL) and secreted significantly more E2 than AMHR2−cells (8.6 pg/mL, P <.05). We conclude that spontaneously differentiated EBs of both mESC and hAdiPSC origin can serve as a biologically relevant model for ovarian GC differentiation and steroidogenic cell commitment. These cells should be further investigated for therapeutic uses, such as stem cell–based hormone replacement therapy and in vitro maturation of oocytes.-
dc.languageeng-
dc.relation.ispartofReproductive Sciences-
dc.subjectsteroidogenesis-
dc.subjectiPSC-
dc.subjectembryonic stem cells-
dc.subjectnative hormones-
dc.subjectovarian tissue regeneration-
dc.titleAn Embryonic and Induced Pluripotent Stem Cell Model for Ovarian Granulosa Cell Development and Steroidogenesis-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1177/1933719117725814-
dc.identifier.scopuseid_2-s2.0-85045680265-
dc.identifier.volume25-
dc.identifier.issue5-
dc.identifier.spage712-
dc.identifier.epage726-
dc.identifier.eissn1933-7205-
dc.identifier.isiWOS:000435535900010-
dc.identifier.issnl1933-7191-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats