ASSOCIATION BETWEEN THE PERCENTAGE OF p16-POSITIVE SENESCENT CELLS AND THE EXPRESSION OF ESTROGEN AND PROGESTERONE RECEPTORS IN HUMAN ENDOMETRIUM DURING THE MID-LUTEAL PHASE

Abstract

Progesterone and estrogen secretion and the expression of their receptors are strongly connected with the cyclic changes in endometrium and its receptivity. We previously reported that the frequency of occurrence of p16-positive senescent cells in human endometrium appear to be also associated with endometrial receptivity and successful embryo implantation. The objective of this study was to analyze the relationship between the percentage of senescent cells and estrogen and progesterone receptors expression in human endometrium during the mid-luteal phase of the menstrual cycle. Prospective observational study. This study includes 383 women who had an endometrial biopsy during the mid-lutheal phase (7 days after LH surge) of the natural cycles. Tissue sections were stained immunohistochemically for ER, PR and p16 using the following monoclonal antibodies: progesterone receptor (PR) (NCL-PGR-312, Leica Microsystems), 1:100 dilution; estrogen receptor (ER) (NCL-L-ER-6F11, Leica Microsystems), 1:100 dilution; p16 ink4a antibody (MAD-000690QD–7, Master Diagnostica), ready-to-use. The percentage of positively stained p16 cells and the levels of ER/PR expression were evaluated by Image-J software (NIH, Maryland, USA) in multiple endometrial sections. Statistical analysis was performed by Spearman’s correlation test using SPSS v.21 (IBM Corp., Armonk, NY, USA). No correlation was found between the frequencies of occurrence of senescent p16-positive stromal, luminal and glandular epithelial cells and PR (p>0.05). In contrast, the glandular expression of ER showed low, but a significant correlation with the percentage of p16+ glandular epithelial cells (R=0.34; p=0.03). In conclusion, we found that the increased cell senescence in endometrial glands during the mid-luteal phase is associated with increased expression of glandular ER in the mid-luteal phase of the cycle. These results suggest an estrogen related change of endometrial senescent cells during the period of embryo implantation.