Abstract:
Angiogenesis plays an important role in the cyclic growth and regression in eutopic endometrium and in the pathogenesis of endometriosis. In the present study the expression patterns of the angiogenic growth factors Angiopoietin-1, Angiopoietin-2 and VEGF-A during the endometrial cycle were studied using quantitative RT-PCR. The expression of the Angiopoietins was also studied in cultured endometrium stimulated with estrogen and progesterone. Furthermore the expression of Angiopoietin-1 and Angiopoietin-2 in endometriosis tissue was quantified.
In endometrial tissue, the quotient Angiopoietin-1/Angiopoietin-2 showed a cyclic trend, which could be described by a cosine estimation graph with a maximum located in mid-cycle. At this time of the menstrual cycle the expression of Angiopoietin-1 outweighed the expression of its antagonist Angiopoietin-2. During the secretory phase the graph declined towards a minimum at the end of the menstrual cycle. Cosine estimation graphs could also be created for the expression patterns of Angiopoietin-1 and Angiopoietin-2. Similarly the expression of the three VEGF-A isoforms studied, VEGF-121, VEGF-165 and VEGF-189, could be described by cosine functions, which only differed in their level. These curves showed maximums in the early proliferative phase and about three days after the middle of the menstrual cycle. Presuming a probability value of p<0.05, the run of all these curves were significant.
Endometrial tissue cultures were stimulated with estradiol and progesteron. Under estradiol treatment a slight increase of the quotient Angiopoietin-1/Angiopoietin-2 was noticed, to which no significance could be attributed. Progesterone-stimulation had no effect either on proliferative or on secretory endometrium. Secretory endometrium stimulated with estradiol showed a non significant increase of the expression of both Angiopoietin subspecies.
In endometriosis tissue, compared with eutopic endometrium, the expression of Angiopoietin-1 and Angiopoietin-2 was significantly increased (p<0.05), a sign of increased angiogenic activity in endometriotic lesions.