The regenerative, proliferative phase of a woman’s menstrual cycle is a critical period which lays the foundation for the subsequent, receptive secretory phase. Although endometrial glands and their secretions are essential for embryo implantation and survival, the proliferative phase, when these glands form, has been rarely examined.
We hypothesised that alterations in the proteome and glycoproteome of idiopathic infertile women would reflect a disturbance in proliferative phase endometrial regeneration. Our aim was to compare the proteomic and glycoproteomic profile of proliferative phase uterine fluid from fertile and infertile women.
Proliferative phase uterine fluids from fertile and infertile women were compared for full proteome (fertile n=9, infertile n=10) and glycoproteome. Proteins with ≥2-fold change (P<0.05) were considered significantly altered between fertile and infertile groups. Glycoproteome analysis employing RCA affinity was used to identify proteins with significantly (P<0.05) altered sugar residues in infertile (n=9) compared to fertile (n=6) women. Immunohistochemistry examined the endometrial localisation of identified proteins, secreted frizzled related protein 4 (SFRP4), CD44, oviduct specific glycoprotein 1 (OVGP1) and isoaspartyl peptidase/L-asparaginase (ASRGL1).
Proteomic analysis identified four proteins significantly downregulated in infertile women compared to fertile women, including, SFRP4 (P=0.026) and CD44 (P=0.029), a further two proteins were upregulated. Seven proteins were unique to the fertile group including OVGP1, six proteins were unique to the infertile group, including ASRGL1. Identified proteins classified into biological processes of tissue regeneration and regulatory processes. ASRGL1 and SFRP4 localised to glandular epithelium and stroma, CD44 to stroma and immune cells, and OVGP1 predominantly stromal. Glycoproteomic analysis identified 7 proteins significantly upregulated including Kallikrein-13 and prothrombin, and 9 proteins significantly downregulated in infertile women including alpha-1-antichymotrypsin.
Our results indicate a disturbance in endometrial development during the proliferative phase among infertile women, providing insights into human endometrial development and potential therapeutic targets for infertility.