Molecular interactions at the bovine embryo-endometrial epithelium interface

Area of Science:

• Reproductive biology
• Genomics
• Mammalian embryology

Background:

• Pre-implantation embryo development in cattle occurs within the uterine lumen.
• Molecular interactions between the embryo and endometrium are crucial for successful pregnancy.
• Limited understanding exists regarding how physical proximity influences these reciprocal interactions.

Purpose of the Study:

• To investigate the impact of physical proximity between bovine endometrial epithelial cells (bEECs) and early-stage embryos (morulae) on their molecular interactions.
• To test the hypothesis that the intensity of embryo-endometrium interactions depends on their physical proximity.

Main Methods:

• Co-culture of bEECs and bovine morulae in juxtacrine (Contact+) and non-juxtacrine (Contact-) settings.
• Transcriptomic analysis of bEECs to identify differentially expressed genes (DEGs) under different co-culture conditions.
• Functional analysis of DEGs to identify affected biological pathways.

Main Results:

• Co-culture with bEECs improved blastocyst rates by day 7.5, irrespective of cell contact.
• Direct contact (Contact+) between bEECs and embryos significantly upregulated endometrial gene transcription (1797 genes) compared to non-contact (230 genes).
• A core set of 50 overlapping DEGs indicated embryo-induced effects on bEEC transcriptome, with pathways including interferon signaling and prostanoid biosynthesis. Contact+ specifically enriched cell cycle regulation and sex-steroid biosynthesis pathways.

Conclusions:

• Physical proximity enhances embryo-endometrium molecular crosstalk, profoundly influencing endometrial gene expression.
• Embryonic signals, modulated by proximity, likely fine-tune endometrial cell function to optimize pregnancy success in cattle.
• These findings provide insights into the mechanisms regulating early pregnancy establishment in livestock.