The progesterone receptor and ubiquitin are differentially regulated within the endometrial glands of the natural and stimulated cycle

The initiation of human pregnancy requires precisely timed development of the endometrium to receive the implanting blastocyst. The ovarian steroid hormones are essential for development and maintenance of a hospitable uterine environment. The hormonal regimes employed in assisted reproduction procedures are known to alter the abundance of specific endometrial receptors for these steroids. Since, in the presence of ligand, the progesterone receptor (PR) is known to be modified by the small intracellular protein ubiquitin, we have investigated the localization of ubiquitin and PR within the endometrial glands of 28 fertile women during a monitored menstrual cycle and also during a stimulated cycle prior to oocyte donation. We have also observed the number of gland cells undergoing cell division as demonstrated by the presence of Ki67 immunostaining, We demonstrate that the percentage of ubiquitin-positive nuclei increases from day four post-ovulation to day 10 post-ovulation in the natural cycle, but that this increase is not seen during a stimulated cycle. The presence of PR within glandular epithelium and the proliferation of gland cells were only observed during the early secretory phase and did not appear to vary significantly between the two cycles. We conclude that ubiquitin may play an important role in endometrial development and that perturbation of ubiquitin may be related to the lower implantation rate seen in the stimulated cycle.