Excessive endometrial angiogenesis is proposed as an important mechanism in the pathogenesis of endometriosis. Evidence is reviewed for the hypothesis that the endometrium of women with endometriosis has an increased capacity to proliferate, implant and grow in the peritoneal cavity. Data is summarized indicating that the endometrium of patients with endometriosis shows enhanced endothelial cell proliferation. Results are also reviewed indicating that the cell adhesion molecule integrin alphavbeta3 is expressed in more blood vessels in the endometrium of women with endometriosis when compared with normal women. Taken together, these results provide evidence for increased endometrial angiogenesis in women with endometriosis when compared with normal subjects. Endometriosis is one of the family of angiogenic diseases. Other angiogenic diseases include solid tumours, rheumatoid arthritis, psoriasis and diabetic retanopathy. Excessive endometrial angiogenesis suggests novel new medical treatments for endometriosis aimed at the inhibition of angiogenesis.

/pdf/angiogenesis-a-new-theory-for-endometriosis-2jygs2o59v.pdf

Angiogenesis: a new theory for endometriosis

PRL production by the decidualized endometrium of early pregnancy was investigated. Endometrium associated with trophoblast (n = 31) was obtained during therapeutic abortions performed 2–6 weeks post conception. Endometrium free of trophoblast (n = 4) was obtained from the uterine cavity immediately after the surgical removal of ectopic pregnancies in which the blastocyst had implanted within the distal portion of a Fallopian tube. When samples of these tissues were incubated in oxygenated Gey's buffer supplemented with 5% fetal calf serum, the concentration of PRL in the medium increased progressively. After 24 h, the total hormone content of the tissue plus medium was significantly greater than the initial hormone content of the tissue before incubation. When protein synthesis was inhibited by the addition of 50 μg/ml cycloheximide to the medium, the amount of PRL produced during incubation was markedly reduced. The four samples of endometrium which contained no tissue of fetal origin due to tubal impla...

Prolactin Production by the Endometrium of Early Human Pregnancy

Morphological alterations in endometrium during the reproductive cycle are increasingly well documented. A new era has now begun in which the molecular processes that underlie these structural changes will be elucidated. Ultimately, in the foreseeable future, the molecular interactions responsible for implantation and placentation will be understood, with undoubted benefits in the clinic. Progress will depend on a combination of biochemical, molecular biological, cell biological, and morphological approaches. This chapter summarizes current information on endometrial composition with emphasis on hormone-regulated alterations in endogenous glycoproteins, proteins, and proteoglycans that may be required for successful reproduction. The main focus of attention is on the human, but results of some animal studies are also included since they may facilitate the establishment of hypotheses for testing, insofar as ethics permit, in the human. New insights into function may be gained when a prominent constituent of one species is absent or modified in another. Emphasis is placed on structural components many of which represent the end products of metabolic processes that are controlled hormonally. The underlying endocrine and metabolic processes themselves are not considered. At the time of writing, few uninterrupted lines of connection can be drawn between morphology and biochemisry, so one function of this chapter is to draw attention to areas of research in which, with recent methodological advances, progress can now be expected.

Cellular Biochemistry of the Endometrium

An indirect immunofluorescent technique was used to determine the localization of cytoplasmic human PRL (hPRL) in fresh and incubated human placental membranes at term. In both fresh and 8-h incubated samples of amnion, amniochorion decidua, or chorion decidua obtained from three placentas, we found specific reproducible localization of hPRL to the cytoplasm of decidua and trophoblast cells. The decidua cells appeared to be the most intensely fluorescent. No specific hPRL immunofluorescence was noted in the amniotic epithelium of fresh or incubated samples of amnion and amniochorion decidua. These data suggest that the trophoblast decidua cell layer is the site of PRL localization and possibly synthesis in placental membranes at term and may be the origin of amniotic fluid PRL in humans.

Indirect Immunofluorescent Localization of Prolactin to the Cytoplasm of Decidua and Trophoblast Cells in Human Placental Membranes at Term

The transport of PRL across human fetal membranes in vitro was studied in Lucite chambers divided by pieces of fresh fetal membranes. The transport of radiolabeled PRL from the medium bathing the decidual surface of the membranes (maternal) across the chorion to the amniotic side of the membranes (fetal) was less than 3% of the total [125I]PRD added to the medium during 2 h of incubation. A similar result was obtained for tracer moving from the amniotic to the maternal side of the membrane. During a similar period o time, 40% of the total radioimmunoassayable PRL originating from within the decidual tissue was released from the tissue and crossed the chorion to the medium bathing the amniotic surface. In the presence of cycloheximide, both the PRL released into the medium and the PRL contained within the tissue were significantly reduced. Colchicine inhibited the transport of PRL from within the decidual tissue without affecting the tissue content ofPRL. The presence or absence of the amnion did not alter...

The Transport of Prolactin by Human Fetal Membranes

AMNIOTIC fluid in man and rhesus monkey contains very high concentrations of prolactin1–3, but its origins are unknown. It does not seem to come from the maternal circulation because isotopically labelled prolactin injected into the pregnant rhesus monkey does not appear in amniotic fluid2. One source of prolactin is suggested by the passage of foetal pituitary prolactin through the immature kidney into the urine and then into amniotic fluid4,5. But amniotic fluid and foetal prolactin differ in molecular size, suggesting different origins4. Incubated human amnion and chorion, but not placenta, release prolactin into the medium, indicating a second source of amniotic fluid prolactin2. Using indirect immunofluorescence, we report localisation of prolactin to the human amnion.

D. L. Healy

Papers

Immunofluorescence shows localisation of prolactin to human amnion.