**6. Theories about the histogenesis of endometriosis**

The many theories proffered to explain the histogenesis of endometriosis may be divided in


The theory of transplantation is the most widely accepted. According to this theory the menstrual flow products flow in a retrograde fashion through the fallopian tubes into the peritoneal cavity. The endometrial products implant, grow and produce tissues with morphology of endometrial glands and stroma. Laparoscopic studies show that during menstruation there is blood in the peritoneal cavity of most women and the retrograde menstrual flow is indeed a usual phenomenon which explains the endometriotic implantation in the ovary and the uterosacral ligaments. Sigmoid colon partly forms a shield and entraps the retrograde menstrual flow products and this fact explains the finding that endometriosis is observed mainly in the left ovary. Also the uterine position is important for the development of endometriosis which is observed anteriorly in patients with anterior uteri. Experimental findings support the transplantation theory and suggest that endometriosis develop in two distinct phases. In the first phase the uterine products are invasive and ovarian hormone -dependent and in the second phase express endogenous estrogen biosynthesis. By the first month after inoculation of primate models with menstrual endometrial tissues these elements attach, grow and invade through the peritoneal mesothelial covering and express estrogen receptor-beta, although aromatase activity is expressed later (Fazleabas et al, 2002 ). Other routes of implantation such as vascular and/or lymphatic spread and direct implantation are reported and explain the development of endometriosis in distant and unusual places such as lung or lymph nodes.

The metaplastic theory proposes that the peritoneum adjacent to ovaries is a multipontential tissue which may obtain characteristics of endometrial tissue (Lauchlan 1972, Lauchlan, 1994). This theory is supported by the observation that endometriosis may develop in cases where no retrograde menstrual flow is possible such as in Rokitansky-Kuster-Hauser syndrome (Acien et al, 1988), in young girls and in men. Finally, according to the induction theory which adds information to transplantation theory, the endometriotic glands and stroma develop de novo from the host tissues, stimulated by the transplanted endometrium.

Most pathologists favor a combination of the metastatic and metaplastic theories and support the theory that endometriosis represents a polygenetic disorder, with alterations in multiple biological pathways (Donnez et al, 2002, Sasson & Taylor, 2008) leading to a metaplastic process under the irritating effect of endometrial tissue shed during retrograde menstrual flow.
