Endometrial cathepsin D immunostaining throughout ovulatory and anovulatory menstrual cycles

The results of histological examination of the endometrium are normal in most patients with unexplained sterility. Cathepsin D is a ubiquitous lysosomal protease regulated by progesterone in the endometrium. Assays of concentrations of cathepsin D might be useful in determining the functional responses of the endometrium to progesterone. To examine this possibility, we quantified immunostaining of endometrial cathepsin D using an image analysis system in women with regular menstrual cycles. An endometrial sample was obtained during the proliferative and luteal phases from 17 women with ovulatory menstrual cycles and at the beginning and during the last 14 days of a cycle from 15 women having anovulatory menstrual cycles. In endometrial glands of ovulatory women, cathepsin D protein immunostaining increased during the cycle and was significantly higher during the luteal than during the proliferative phase [51 +/- 38.1 arbitrary units (AU) versus 118.2 +/- 58.9 AU; P < 0.01]. This increase was also observed in stromal cells, although to a lesser extent (28.6 +/- 26.9 versus 41.5 +/- 43.1 AU; P = NS). In the endometrium of women with anovulatory menstrual cycles, cathepsin D staining was high both for the proliferative and the luteal biopsies in glands (respectively 95 +/- 43 and 104 +/- 51.3 AU) and stromal cells (respectively 61.8 +/- 33.8 and 75 +/- 32.6 AU). In women with ovulatory cycles, cathepsin D staining was localized in the apical part of glandular cells during the proliferative phase and diffused throughout the cytoplasm during the luteal phase. In contrast, in women with anovulatory cycles, cellular localization of cathepsin D remained apical in glands, regardless of the day of biopsy. In conclusion, this study shows that the cytoplasmic localization of cathepsin D might be a qualitative biological indicator of endometrial gland responses to progesterone. This could be a useful tool for evaluating cell function, which is poorly tested by histology alone.