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

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3 Citations (Scopus)


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
Publication statusPublished - Jan 2022

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