Effect of cumulin and super-GDF9 in standard and biphasic mouse IVM

Nazli Akin, Dulama Richani, Xiuhua Liao, Yiqing Zhao, Anamaria-Cristina Herta, Katy Billooye, William A Stocker, David G Mottershead, Craig A Harrison, Johan Smitz, Ellen Anckaert, Robert B Gilchrist

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)
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PURPOSE: In vitro maturation (IVM) is a technology that generates mature oocytes following culture of immature cumulus-oocyte complexes (COC) in vitro. IVM is characterized by minimal patient stimulation, making it attractive for certain patient groups. Recently, a biphasic IVM system, capacitation (CAPA)-IVM, has shown improved clinical outcomes relative to standard IVM; however, it remains less efficient than IVF. This study assessed whether supplementation of CAPA-IVM culture media with the novel TGFβ superfamily proteins cumulin and super-GDF9 improves subsequent mouse embryo development.

METHODS: Immature mouse COCs were cultured by standard IVM or biphasic IVM ± cumulin or super-GDF9.

RESULTS: Both cumulin and super-GDF9 in standard IVM significantly improved day-6 blastocyst rate (53.9% control, 73.6% cumulin, 70.4% super-GDF9; p = 0.006; n = 382-406 oocytes). Cumulin or super-GDF9 in CAPA-IVM did not alter embryo yield or blastocyst cell allocation in an unstimulated model. Moreover, cumulin did not alter these outcomes in a mild PMSG stimulation model. Cumulin in CAPA-IVM significantly increased cumulus cell expression of cumulus expansion genes (Ptgs2, Ptx3, Adamts1, Gfat2) and decreased Lhr expression relative to control. However, cumulin-induced mRNA expression of cumulus cell (Ptgs2, Ptx3) and oocyte genes (Gdf9, Bmp15, Oct4, Stella) in CAPA-IVM remained significantly lower than that of in vivo matured cells.

CONCLUSION: Cumulin did not provide an additional beneficial effect in biphasic IVM in terms of blastocyst yield and cell allocation; however in standard IVM, cumulin and super-GDF9 significantly improve oocyte developmental competence.

Original languageEnglish
Pages (from-to)127-140
Number of pages14
JournalJournal of Assisted Reproduction and Genetics
Issue number1
Early online date4 Jan 2022
Publication statusPublished - Jan 2022

Bibliographical note

© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.


  • In vitro maturation
  • mature oocytes
  • cumulus-oocyte complexes
  • capacitation (CAPA)-IVM
  • mouse
  • culture


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