Barbara Gaffuri

Expression of GnRH receptor gene in human ectopic endometrial cells and inhibition of their proliferation by leuprolide acetate.

The present study was conducted to investigate whether GnRH-receptor (GnRH-R) gene is expressed in endometriosis ovarian implants and whether a GnRH-analogue (GnRH-a) may exert an effect on endometriosis cell proliferation in vitro. The presence of GnRH-R transcripts in ovarian endometriosis cells was assessed by reverse transcription-polymerase chain reaction (RT-PCR) and further confirmed by Southern blot analysis. GnRH-R mRNA was detected in all the 13 samples examined. In contrast, GnRH-R transcripts were not detectable in endometriosis-free peritoneal tissue. In the second part of the study, endometriosis cells were cultured for 9 days with different doses of leuprolide acetate (ranging from 0 to 10(-5) M). In 4 out of 13 cases, a significant anti-proliferative effect was observed at doses of leuprolide acetate ranging from 10(-9) to 10(-5) M. In one case, a significant inhibition of cell proliferation was observed only at 10(-5) M leuprolide acetate concentration. In contrast, the GnRH-a did not affect cell growth, regardless of the expression of GnRH-R transcripts and the given doses, in the remaining 8 experiments. To date, this is the first evidence indicating that GnRH-R mRNA is expressed in human ovarian endometriomas. Moreover, the inhibition of endometriosis cell proliferation induced by the GnRH-a in vitro suggests that, at least in some cases, this compound might exert a direct effect on endometriosis lesions.

Modulation of NK Cell Lytic Function by Endometrial Secretory Factors: Potential Role in Endometriosis

PROBLEM: Development and progression of endometriosis have been suggested to be related to a defect of NK cells in the ability to eliminate endometrial fragments regurgitated with menstrual debris in ectopic sites. However, it has not been clarified yet whether the origin of this defect has to be attributed to an intrinsic alteration of NK cell population or to a consequence of the environmental system. The present study was designed to evaluate whether soluble factors of endometrial origin might directly interfere with NK cell lytic function.

Endometrial release of soluble intercellular adhesion molecule 1 and endometriosis: Relationship to the extent of the disease

Objective To relate endometrial release of the soluble form of intercellular adhesion molecule 1 with extent of endometriosis. Methods Samples of endometrium were collected from 23 women with endometriosis. Soluble intercellular adhesion molecule 1 was quantified in conditioned medium from 48-hour endometrial stromal cell cultures with use of a specific enzyme-linked immunosorbent assay. Levels were correlated with revised American Society for Reproductive Medicine classification score for adhesions, implants, and cysts and total score; number of endometriotic implants; cyst diameter; and presence or absence of pelvic pain symptoms and previous surgical procedures for endometriosis. Results Endometrial release of soluble intercellular adhesion molecule 1 directly correlated with number of implants (r = .64, P < .005) and score for implants (r = .61, P < .005). There was no significant correlation between levels of the soluble molecule and score for adhesions or total score. Soluble intercellular adhesion molecule 1 shed by endometrium did not correlate with the score for ovarian cysts, although an inverse relationship was found with ovarian cyst diameter (r = −0.52, P < .05). No differences were detected between women who had pelvic pain and those who did not and between those who had previous surgery for endometriosis and those who had not. Conclusion The association between endometrial release of soluble intercellular adhesion molecule 1 and the number and score of endometriotic implants suggests that the molecule might be of value in evaluating spread potential of refluxed endometrium.

Soluble Intercellular Adhesion Molecule-1 Serum Profile in Physiologic and Preeclamptic Pregnancy

PROBLEM: The aim of this study was to determine serum levels of soluble intercellular adhesion molecule (sICAM)‐1, an adhesion receptor that mediates interactions with the immune system, in physiologic and preeclamptic pregnancies. Moreover, we evaluated whether the release of sICAM‐1 during pregnancy correlated to plasma fibronectin concentrations.

Comparative Effect of the Calcium Antagonist Verapamil and the Synthetic Steroids Gestrinone and Danazol on Human Monocyte Phagocytosis in vitro

Recent evidence suggested that periovulatory treatment with an immunomodulatory agent such as verapamil might be an effective alternative to conventional treatment for endometriosis-associated subfertility. In particular, it has been reported that the drug might reduce the accentuated macrophage peritoneal activation demonstrated in patients with endometriosis. In this study, we compared the effect of the calcium antagonist verapamil with those of gestrinone, danazol and testosterone on human monocyte phagocytosis in an attempt to evaluate any significant differences in their ability to influence a parameter of cell inflammatory activation. Peripheral blood monocytes were isolated from 37 healthy women. Monocyte function was determined by phagocytosis of fluorescent microspheres after an overnight incubation in the presence or absence of the various agents. This study indicates that verapamil at the pharmacological concentration of 0.4 micrograms/ml, the systemic level in patients taking 40-80 mg/8 h p.o., significantly inhibits monocyte function. A lower immunosuppressive but still significant effect was achieved in this assay system with gestrinone at a concentration of 3 x 10(-8) M). The pharmacological concentration of danazol (10(-6) M) and the physiologic concentration of testosterone (10(-8) M) did not significantly affect this immunologic test system. These results provide evidence that verapamil is able to exert a slightly greater immunosuppressive effect than steroidal drugs on monocyte phagocytosis. However, due to the small differences observed, further studies on the biological mechanism of the drug seem to be necessary to completely elucidate its potential role in endometriosis-associated subfertility.