In Vitro Folliculogenesis in Mammalian Models: A Computational Biology Study
In vitro folliculogenesis (ivF) has been proposed as an emerging technology to support follicle growth and oocyte development. It holds a great deal of attraction from preserving human fertility to improving animal reproductive biotechnology. Despite the mice model, where live offspring have been ac...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:18ba53fa81c7401b931f738afa4db7ad2021-11-09T05:35:53ZIn Vitro Folliculogenesis in Mammalian Models: A Computational Biology Study2296-889X10.3389/fmolb.2021.737912https://doaj.org/article/18ba53fa81c7401b931f738afa4db7ad2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmolb.2021.737912/fullhttps://doaj.org/toc/2296-889XIn vitro folliculogenesis (ivF) has been proposed as an emerging technology to support follicle growth and oocyte development. It holds a great deal of attraction from preserving human fertility to improving animal reproductive biotechnology. Despite the mice model, where live offspring have been achieved,in medium-sized mammals, ivF has not been validated yet. Thus, the employment of a network theory approach has been proposed for interpreting the large amount of ivF information collected to date in different mammalian models in order to identify the controllers of the in vitro system. The WoS-derived data generated a scale-free network, easily navigable including 641 nodes and 2089 links. A limited number of controllers (7.2%) are responsible for network robustness by preserving it against random damage. The network nodes were stratified in a coherent biological manner on three layers: the input was composed of systemic hormones and somatic-oocyte paracrine factors; the intermediate one recognized mainly key signaling molecules such as PI3K, KL, JAK-STAT, SMAD4, and cAMP; and the output layer molecules were related to functional ivF endpoints such as the FSH receptor and steroidogenesis. Notably, the phenotypes of knock-out mice previously developed for hub.BN indirectly corroborate their biological relevance in early folliculogenesis. Finally, taking advantage of the STRING analysis approach, further controllers belonging to the metabolic axis backbone were identified, such as mTOR/FOXO, FOXO3/SIRT1, and VEGF, which have been poorly considered in ivF to date. Overall, this in silico study identifies new metabolic sensor molecules controlling ivF serving as a basis for designing innovative diagnostic and treatment methods to preserve female fertility.Nicola BernabòNicola BernabòChiara Di BerardinoGiulia CapacchiettiAlessia PesericoGiorgia BuoncuoreUmberto TosiMartina CrociatiMartina CrociatiMaurizio MonaciMaurizio MonaciBarbara BarboniFrontiers Media S.A.articleovarian folliculogenesiscomputational biologyIn vitro folliculogenesis networkhub moleculesbottleneck moleculesBiology (General)QH301-705.5ENFrontiers in Molecular Biosciences, Vol 8 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
ovarian folliculogenesis computational biology In vitro folliculogenesis network hub molecules bottleneck molecules Biology (General) QH301-705.5 |
| spellingShingle |
ovarian folliculogenesis computational biology In vitro folliculogenesis network hub molecules bottleneck molecules Biology (General) QH301-705.5 Nicola Bernabò Nicola Bernabò Chiara Di Berardino Giulia Capacchietti Alessia Peserico Giorgia Buoncuore Umberto Tosi Martina Crociati Martina Crociati Maurizio Monaci Maurizio Monaci Barbara Barboni In Vitro Folliculogenesis in Mammalian Models: A Computational Biology Study |
| description |
In vitro folliculogenesis (ivF) has been proposed as an emerging technology to support follicle growth and oocyte development. It holds a great deal of attraction from preserving human fertility to improving animal reproductive biotechnology. Despite the mice model, where live offspring have been achieved,in medium-sized mammals, ivF has not been validated yet. Thus, the employment of a network theory approach has been proposed for interpreting the large amount of ivF information collected to date in different mammalian models in order to identify the controllers of the in vitro system. The WoS-derived data generated a scale-free network, easily navigable including 641 nodes and 2089 links. A limited number of controllers (7.2%) are responsible for network robustness by preserving it against random damage. The network nodes were stratified in a coherent biological manner on three layers: the input was composed of systemic hormones and somatic-oocyte paracrine factors; the intermediate one recognized mainly key signaling molecules such as PI3K, KL, JAK-STAT, SMAD4, and cAMP; and the output layer molecules were related to functional ivF endpoints such as the FSH receptor and steroidogenesis. Notably, the phenotypes of knock-out mice previously developed for hub.BN indirectly corroborate their biological relevance in early folliculogenesis. Finally, taking advantage of the STRING analysis approach, further controllers belonging to the metabolic axis backbone were identified, such as mTOR/FOXO, FOXO3/SIRT1, and VEGF, which have been poorly considered in ivF to date. Overall, this in silico study identifies new metabolic sensor molecules controlling ivF serving as a basis for designing innovative diagnostic and treatment methods to preserve female fertility. |
| format |
article |
| author |
Nicola Bernabò Nicola Bernabò Chiara Di Berardino Giulia Capacchietti Alessia Peserico Giorgia Buoncuore Umberto Tosi Martina Crociati Martina Crociati Maurizio Monaci Maurizio Monaci Barbara Barboni |
| author_facet |
Nicola Bernabò Nicola Bernabò Chiara Di Berardino Giulia Capacchietti Alessia Peserico Giorgia Buoncuore Umberto Tosi Martina Crociati Martina Crociati Maurizio Monaci Maurizio Monaci Barbara Barboni |
| author_sort |
Nicola Bernabò |
| title |
In Vitro Folliculogenesis in Mammalian Models: A Computational Biology Study |
| title_short |
In Vitro Folliculogenesis in Mammalian Models: A Computational Biology Study |
| title_full |
In Vitro Folliculogenesis in Mammalian Models: A Computational Biology Study |
| title_fullStr |
In Vitro Folliculogenesis in Mammalian Models: A Computational Biology Study |
| title_full_unstemmed |
In Vitro Folliculogenesis in Mammalian Models: A Computational Biology Study |
| title_sort |
in vitro folliculogenesis in mammalian models: a computational biology study |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/18ba53fa81c7401b931f738afa4db7ad |
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