Human embryo implantation is a multistep process requiring both receptive endometrium and a good quality embryo at the blastocyst stage. During the midsecretory (receptive) phase of the menstrual cycle, the endometrial epithelial cells secrete factors that promote blastocyst attachment. These factors may provide markers that can reliably identify receptive endometrium to improve IVF. Apolipoprotein E (ApoE) was reported as the most up-regulated gene in receptive endometrium1. Despite being highly expressed in the endometrium, the secretion of ApoE and other apolipoproteins (ApoAI, ApoAII, ApoB, ApoCII and ApoCIII) into the endometrial cavity and their potential role in endometrial receptivity has not been characterised.
We hypothesised that apolipoproteins present in the uterine cavity influence uterine receptivity. We aimed to establish the presence, concentrations and cellular source of apolipoproteins in uterine fluid in fertile and infertile women.
Immunohistochemistry was used to determine localization and expression of apolipoproteins across the menstrual cycle in uterine tissue. Concentrations of apolipoproteins AI, AII, B, CII, CIII and E were measured in uterine lavage from proliferative, early-secretory and midsecretory phases of the menstrual cycle of fertile (n=13, 10, 6 respectively) and infertile (n=11, 10, 6 respectively) women, using the Luminex® multiplex analysis system.
Immunohistochemistry confirmed the presence of these proteins in the luminal and glandular epithelial cells in endometrial biopsies. The concentration of apolipoproteins AII, CII and CIII in endometrial fluid were significantly increased (p=0.008, p=0.006 and p=0.012 respectively) during the midsecretory phase of infertile compared with fertile subjects. Although not significant, ApoAI, ApoB and ApoE concentrations were somewhat elevated during the midsecretory phase of infertile compared to fertile subjects (p=0.065, p=0.060, p=0.063) respectively.
In conclusion, apolipoproteins are present in uterine fluid, with elevated concentrations in samples from infertile women. Thus, apolipoproteins may have an important local role in endometrial receptivity.