TY - JOUR
T1 - Rescue in vitro maturation using ovarian support cells of human oocytes from conventional stimulation cycles yields oocytes with improved nuclear maturation and transcriptomic resemblance to in vivo matured oocytes
AU - Paulsen, Bruna
AU - Piechota, Sabrina
AU - Barrachina, Ferran
AU - Giovannini, Alexa
AU - Kats, Simone
AU - Potts, Kathryn S.
AU - Rockwell, Graham
AU - Marchante, Maria
AU - Estevez, Samantha L.
AU - Noblett, Alexander D.
AU - Figueroa, Alexandra B.
AU - Aschenberger, Caroline
AU - Kelk, Dawn A.
AU - Forti, Marcy
AU - Marcinyshyn, Shelby
AU - Wiemer, Klaus
AU - Sanchez, Marta
AU - Belchin, Pedro
AU - Lee, Joseph A.
AU - Buyuk, Erkan
AU - Slifkin, Rick E.
AU - Smela, Merrick Pierson
AU - Fortuna, Patrick R.J.
AU - Chatterjee, Pranam
AU - McCulloh, David H.
AU - Copperman, Alan B.
AU - Ordonez-Perez, Daniel
AU - Klein, Joshua U.
AU - Kramme, Christian C.
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/8
Y1 - 2024/8
N2 - Purpose: Determine if the gene expression profiles of ovarian support cells (OSCs) and cumulus-free oocytes are bidirectionally influenced by co-culture during in vitro maturation (IVM). Methods: Fertility patients aged 25 to 45 years old undergoing conventional ovarian stimulation donated denuded immature oocytes for research. Oocytes were randomly allocated to either OSC-IVM culture (intervention) or Media-IVM culture (control) for 24–28 h. The OSC-IVM culture condition was composed of 100,000 OSCs in suspension culture with human chorionic gonadotropin (hCG), recombinant follicle stimulating hormone (rFSH), androstenedione, and doxycycline supplementation. The Media-IVM control lacked OSCs and contained the same supplementation. A limited set of in vivo matured MII oocytes were donated for comparative evaluation. Endpoints consisted of MII formation rate, morphological and spindle quality assessment, and gene expression analysis compared to in vitro and in vivo controls. Results: OSC-IVM resulted in a statistically significant improvement in MII formation rate compared to the Media-IVM control, with no apparent effect on morphology or spindle assembly. OSC-IVM MII oocytes displayed a closer transcriptomic maturity signature to IVF-MII controls than Media-IVM control MII oocytes. The gene expression profile of OSCs was modulated in the presence of oocytes, displaying culture- and time-dependent differential gene expression during IVM. Conclusion: The OSC-IVM platform is a novel tool for rescue maturation of human oocytes, yielding oocytes with improved nuclear maturation and a closer transcriptomic resemblance to in vivo matured oocytes, indicating a potential enhancement in oocyte cytoplasmic maturation. These improvements on oocyte quality after OSC-IVM are possibly occurring through bidirectional crosstalk of cumulus-free oocytes and ovarian support cells.
AB - Purpose: Determine if the gene expression profiles of ovarian support cells (OSCs) and cumulus-free oocytes are bidirectionally influenced by co-culture during in vitro maturation (IVM). Methods: Fertility patients aged 25 to 45 years old undergoing conventional ovarian stimulation donated denuded immature oocytes for research. Oocytes were randomly allocated to either OSC-IVM culture (intervention) or Media-IVM culture (control) for 24–28 h. The OSC-IVM culture condition was composed of 100,000 OSCs in suspension culture with human chorionic gonadotropin (hCG), recombinant follicle stimulating hormone (rFSH), androstenedione, and doxycycline supplementation. The Media-IVM control lacked OSCs and contained the same supplementation. A limited set of in vivo matured MII oocytes were donated for comparative evaluation. Endpoints consisted of MII formation rate, morphological and spindle quality assessment, and gene expression analysis compared to in vitro and in vivo controls. Results: OSC-IVM resulted in a statistically significant improvement in MII formation rate compared to the Media-IVM control, with no apparent effect on morphology or spindle assembly. OSC-IVM MII oocytes displayed a closer transcriptomic maturity signature to IVF-MII controls than Media-IVM control MII oocytes. The gene expression profile of OSCs was modulated in the presence of oocytes, displaying culture- and time-dependent differential gene expression during IVM. Conclusion: The OSC-IVM platform is a novel tool for rescue maturation of human oocytes, yielding oocytes with improved nuclear maturation and a closer transcriptomic resemblance to in vivo matured oocytes, indicating a potential enhancement in oocyte cytoplasmic maturation. These improvements on oocyte quality after OSC-IVM are possibly occurring through bidirectional crosstalk of cumulus-free oocytes and ovarian support cells.
KW - Granulosa cells
KW - In vitro maturation
KW - Oocyte transcriptomics
KW - Ovarian support cells
KW - Stem cells
UR - http://www.scopus.com/inward/record.url?scp=85194893311&partnerID=8YFLogxK
U2 - 10.1007/s10815-024-03143-4
DO - 10.1007/s10815-024-03143-4
M3 - Article
C2 - 38814543
AN - SCOPUS:85194893311
SN - 1058-0468
VL - 41
SP - 2021
EP - 2036
JO - Journal of Assisted Reproduction and Genetics
JF - Journal of Assisted Reproduction and Genetics
IS - 8
ER -