Frauenklinik, Klinikum Darmstadt, Grafenstrasse 9, 64283 Darmstadt, Germany e-mail: leyendecker{at}ferticonsult.de
Dear Sir,
We thank Drs DHooghe and Debrock for their interest in our paper (Leyendecker et al., 2002) and the questions they raise in their letter: (i) women with endometriosis desquamate fragments of basal endometrium while women without endometriosis do notat least to a significantly lesser extent. This explains the difference. (ii) The amount of desquamated endometrial tissue on day two of the cycle might vary considerably between patients. In order to circumvent this confounding variable we chose to take only one section of the collected tissue of the menstrual blood specimen for staining of each the markers. Thus, applying this method, we found for example that in 75% of the women with endometriosis estradiol receptor positive endometrial fragments were shed while this marker of basal endometrium was only positive in menstrual blood tissue fragments in 10% of the women without endometriosis. There are certainly other markers than those used in our study available for the differentiation between tissue elements derived from the functionalis and the basalis.
The menstrual blood specimens were all processed in one work-up. Thus, although not specifically intended, the investigator did not know whether the respective patient had endometriosis or not. By the way, now we know that it is very simple to discriminate between functionalis and deep basalis merely on morphological appearance, such as the shape of the nuclei and their position within the cell of the epithelium. We did not find it necessary to apply the immunoreactive score (IRS) to the menstrual blood specimen. With the IRS we could demonstrate a cyclically changing pattern of receptor expression. With respect to the menstrual blood we answered a yes or no question. (iii) Indeed we cannot exclude the possibility described by Drs DHooghe and Debrock in their letter. In the discussion section of our paper we state that "there is no direct proof available but it is reasonable to assume that the endometriotic peritoneal lesions result from the implantation and growth of retrogradely shed basalis rather than from shed functionalis". This reasoning refers to what was outlined before with respect to the characteristics of the functionalis and basalis at the end of the secretory phase such as mitotic activity, equipment with receptors and enzymes and so forth. Moreover, a striking difference between patients with and without endometriosis is the shedding of basalis in women with the disease. Furthermore, we point out that basal endometrium has the potential to form all archimetrial tissue components such as epithelium, stroma and smooth muscle cells. Of course, this all is circumstantial evidence as stated in our paper. In view of all these data the suggestion made by DHooghe and Debrock (2003) that shed functionalis would implant and de-differentiate into basalis appears far less probable.
To the best of our knowledge the development of endometriosis has not before been associated to the eutopic basal endometrium. Interestingly, the only study that mentioned but discarded this possibility is the paper by DHooghe et al. (1995) They performed subperitoneal injections and intraperitoneal seeding of fragments of eutopic endometrial tissue obtained by transfundal or transcervical endometrial biopsy during the different phases of the cycle. The transplantation of menstrual endometrium obtained on day two of the cycle resulted in significantly more endometriotic lesions than that of luteal endometrium. They discussed that "...it is likely that basal endometrial cells were also obtained during endometrial biopsy, because multiple biopsies were taken in each animal to have a large amount of tissue for induction. However, the proportion of basal cells is a confounding variable for any endometrial biopsy whether taken during the menstrual or luteal phase...". Taking into consideration that on day two of the cycle, basal endometrium might be exposed or only covered by a small fringe of spongiosa it is very likely that vigorous biopsies yielded plenty of basal endometrium during menstrual phase and possibly also some basal endometrium during the luteal phase. This could explain the different outcomes of the transplantation experiments. DHooghe and co-workers were pretty close to our concept, but arrived at other conclusions. At that time there was an astonishing dearth in information on the human basal endometrium and there were no data available indicating that fragments of basal endometrium were shed during menstruation particularly in women with endometriosis. These data were provided for the first time in our paper. Nevertheless, a re-interpretation of the data of DHooghe et al. (1995
) adds further circumstantial evidence to our concept of endometriosis resulting from the dislocation of basal endometrium.
References
DHooghe, T.M. and Debrock, S. (2003) Evidence that ndometriosis results from the dislocation of basal endometrium? Hum. Reprod., 18, 0000.
DHooghe, T.M., Bambra, C.S., Raeymaekers, B.M., De Jonge, I., Lauweryns, J.M. and Koninckx, P.R. (1995) Intrapelvic injection of menstrual endometrium causes endometriosis in baboons (Papio cynocephalus and Papio anubis). Am. J. Obstet. Gynecol., 173, 125134.[CrossRef][ISI][Medline]
Leyendecker, G., Herbertz, M., Kunz, G. and Mall, G. (2002). Endometriosis results from the dislocation of basal endometrium. Hum. Reprod., 17, 27252736.