Molecular profiling of human blastocysts reveals primitive endoderm defects among embryos of decreased implantation potential
Jennifer N. Chousal,
Robert Morey,
Srimeenakshi Srinivasan,
Katherine Lee,
Wei Zhang,
Ana Lisa Yeo,
Cuong To,
Kyucheol Cho,
V. Gabriel Garzo,
Mana M. Parast,
Louise C. Laurent,
Heidi Cook-Andersen
Affiliations
Jennifer N. Chousal
Department of Pathology, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
Robert Morey
Department of Pathology, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
Srimeenakshi Srinivasan
Department of Obstetrics, Gynecology, and Reproductive Sciences, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
Katherine Lee
Department of Obstetrics, Gynecology, and Reproductive Sciences, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Department of Molecular Biology, University of California, San Diego, La Jolla, CA 92093, USA
Wei Zhang
Reproductive Partners Fertility Center – San Diego, La Jolla, CA 92037, USA
Ana Lisa Yeo
Reproductive Partners Fertility Center – San Diego, La Jolla, CA 92037, USA
Cuong To
Department of Obstetrics, Gynecology, and Reproductive Sciences, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
Kyucheol Cho
Department of Obstetrics, Gynecology, and Reproductive Sciences, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
V. Gabriel Garzo
Reproductive Partners Fertility Center – San Diego, La Jolla, CA 92037, USA
Mana M. Parast
Department of Pathology, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
Louise C. Laurent
Department of Obstetrics, Gynecology, and Reproductive Sciences, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
Heidi Cook-Andersen
Department of Obstetrics, Gynecology, and Reproductive Sciences, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Department of Molecular Biology, University of California, San Diego, La Jolla, CA 92093, USA; Corresponding author
Summary: Human embryo implantation is remarkably inefficient, and implantation failure remains among the greatest obstacles in treating infertility. Gene expression data from human embryos have accumulated rapidly in recent years; however, identification of the subset of genes that determine successful implantation remains a challenge. We leverage clinical morphologic grading—known for decades to correlate with implantation potential—and transcriptome analyses of matched embryonic and abembryonic samples to identify factors and pathways enriched and depleted in human blastocysts of good and poor morphology. Unexpectedly, we discovered that the greatest difference was in the state of extraembryonic primitive endoderm (PrE) development, with relative deficiencies in poor morphology blastocysts. Our results suggest that implantation success is most strongly influenced by the embryonic compartment and that deficient PrE development is common among embryos with decreased implantation potential. Our study provides a valuable resource for those investigating the markers and mechanisms of human embryo implantation.
