Uterine fluid is essential for the development of embryos and blastocyst implantation. Uterine fluid is secreted by the endometrial glands and is composed of the necessary substances for embryo development including metabolites, proteins, lipids, and hormones.
In eutherian mammals, trophoblast cells form the placenta post-implantation which then provides nutrients and gas exchange for the developing fetus. The role of uterine fluid in eutherians has previously been investigated prior to and at the time of implantation, however, the importance of uterine fluid post-implantation, particularly in later stages of gestation is not well understood.
Mouse embryos are routinely grown to blastocysts using commercial media to investigate pre-implantation embryo development. However, development beyond blastocysts in culture has previously been challenging. Recent advances in mouse assisted reproductive technologies (ART) by others have demonstrated that pre-gastrulation mouse embryos can be cultured until advanced organogenesis ex utero.
To extend embryo development in culture conditions, we aim to identify key components of post-implantation uterine fluid in mice utilising a multi-omics approach. Uterine fluid of mice has been collected at early-, mid- and late-gestation.
Pathway analyses of metabolomics and proteomics similarly demonstrate separation of mid (e6.5 and e10.5) and later (e14.5 and e18.5) stages of gestation, indicating a shift in the components of uterine fluid. Preliminary lipidomics results also demonstrate a large shift in the lipid profile in the later stages.
These analyses indicate that drastically different media compositions are likely required for post-implantation mouse embryo culture compared to pre-implantation. We will test these media formulations utilising our custom-built ex-utero culture devices. Identifying culture requirements at specific timepoints could improve ART conditions and may enable ex-utero survival and development of embryos beyond what has previously been achieved. This multi-omics approach will enhance our understanding of how uterine fluid impacts embryo development across the course of gestation, particularly, post-implantation.