Paul J.Q. van der Linden

Deventer Ziekenhuis, Department of Obstetrics and Gynecology, P.O. Box 5001, 7400 GC Deventer, The Netherlands

Received 6/15/97 Accepted 7/29/97

3. MAIN CONCEPTS

3.1 In situ development theory
The theories considering the development of endometriosis from either the Wolffian duct or knob or from Müllerian tissue have been met with a lot of opposition over the years and for the most part have been disregarded. The finding of endometriosis on the serosal surface of the colon and the small intestines made a purely embryonic derivation too restrictive. The theory of coelomic metaplasia has still some support, because it can explain the origin of endometriosis, regardless of the sites or the conditions of its occurrence (11). The theory does not explain why endometriosis occurs exclusively in women, typically during the reproductive years, or why endometriosis mainly affects the pelvic organs, or why it only occurs in women with a functioning endometrium. Proof of this theory is lacking, either experimentally or clinically. There is only some circumstantial evidence, in case reports, of endometriosis occurring in young girls, even before menarche, and in reports of endometriosis at rare locations, such as pleura or diaphragma (12, 13).

3.2 Induction theory
In 1955, Levander and Normann introduced the induction theory (7). This theory is based on the assumption that specific substances which are released by the degenerating endometrium induce endometriosis from omnipotent blastema, present in connective tissues. This theory was proposed since, in experiments in rabbits, cell-free endometrial products were capable of inducing endometrial metaplasia (8). These changes, however, do not meet the criteria for the diagnosis of endometriosis, since no endometrial stroma was found in these experiments.  Lauchlan introduced the term "secondary Müllerian system", referring to all Müllerian type epithelium located outside the course of the original Müllerian ducts (6). This layer of cells could then, particularly on the surface of the ovary, through metaplasia develop into four cell types, serous (tubal), mucinous (endocervical), Brenner epithelium, and endometrial. This could occur before or after invagination, particularly of the ovary. The fact that both serous and mucinous epithelium can be found in or around endometriotic lesions is an argument in favor of this concept (6).

3.3 Implantation theory
The implantation theory is based on the principle that viable endometrium implants on the peritoneal surface. Therefore this theory requires three steps. First, retrograde menstruation has to occur. Secondly, retrograde menstruation should contain viable endometrial cells, and, thirdly, adhesion to the peritoneum has to occur with subsequent implantation and proliferation. The implantation theory was originally neglected for a long time, because menstrual effluent was considered to contain only non-viable endometrial tissue and retrograde menstruation was thought to be a rare phenomenon (14, 15, 16, 17).

Retrograde menstruation and peritoneal adhesion of endometrial tissue is an essential element in the pathogenesis of endometriosis according to the Sampson theory (9, 10, 18). Menstruation is almost unique to human beings and a few other primates. Only recently, menstruation and menstrual shedding has been associated with disorgainzation of the site-specific distribution of desmoplakin I/II, E-cadherin, and alpha- and beta catenins (19). Menstrual effluent is composed of blood elements, endometrial cells and extracellular fluid. Menstrual effluent does contain viable endometrial cells as shown in the classical study of Keettel and Stein in 1951 (20). Cron and Gey tried earlier to prove the viability of the cast-off menstrual endometrium in culture However, they curetted the endometrium to obtain tissue for their experiments (21). Geist suggested that desquamation of endometrium was not due to necrosis, since menstrual effluent contained viable endometrial cells, that remained alive for at least one hour (22). Ridley and Edwards demonstrated, in 1958, that endometrial cells obtained from the menstrual effluent could be implanted into the abdominal wall fascia (23). However, only in one of 8 cases they succeeded in finding endometriosis developing at the site of injection.
The prerequisites for the implantation theory are discussed in further detail in the following section.