The effects of aging on molecular modulators of human embryo implantation
Panagiotis Ntostis,
Grace Swanson,
Georgia Kokkali,
David Iles,
John Huntriss,
Agni Pantou,
Maria Tzetis,
Konstantinos Pantos,
Helen M. Picton,
Stephen A. Krawetz,
David Miller
Affiliations
Panagiotis Ntostis
Discovery and Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, LS2 9JT, UK; Genetics Department, Medical school, National and Kapodistrian University of Athens, Athens, 115 27, Greece; Corresponding author
Grace Swanson
Department of Obstetrics and Gynecology and the Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201, USA
Georgia Kokkali
Genesis Athens Clinic, Reproductive Medicine Unit, Athens, 152 32, Greece
David Iles
Discovery and Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, LS2 9JT, UK
John Huntriss
Discovery and Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, LS2 9JT, UK
Agni Pantou
Genesis Athens Clinic, Reproductive Medicine Unit, Athens, 152 32, Greece
Maria Tzetis
Genetics Department, Medical school, National and Kapodistrian University of Athens, Athens, 115 27, Greece
Konstantinos Pantos
Genesis Athens Clinic, Reproductive Medicine Unit, Athens, 152 32, Greece
Helen M. Picton
Discovery and Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, LS2 9JT, UK
Stephen A. Krawetz
Department of Obstetrics and Gynecology and the Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201, USA
David Miller
Discovery and Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, LS2 9JT, UK; Corresponding author
Summary: Advancing age has a negative impact on female fertility. As implantation rates decline during the normal maternal life course, age-related, embryonic factors are altered and our inability to monitor these factors in an unbiased genome-wide manner in vivo has severely limited our understanding of early human embryo development and implantation. Our high-throughput methodology uses trophectoderm samples representing the full spectrum of maternal reproductive ages with embryo implantation potential examined in relation to trophectoderm transcriptome dynamics and reproductive maternal age. Potential embryo-endometrial interactions were tested using trophectoderm sampled from young women, with the receptive uterine environment representing the most ‘fertile’ environment for successful embryo implantation. Potential roles for extracellular exosomes, embryonic metabolism and regulation of apoptosis were revealed. These biomarkers are consistent with embryo-endometrial crosstalk/developmental competency, serving as a mediator for successful implantation. Our data opens the door to developing a diagnostic test for predicting implantation success in women undergoing fertility treatment.
