Role of nitric oxide and bcl-2 family genes in the regulation of human endometrial apoptosis

Objective: To investigate the role of nitric oxide (NO) and death regulatory genes, bcl-2 and bax, in human endometria apoptosis. Design: Expression of bcl-2, bax, NO synthases (NOS), and the apoptotic effect Of L-arginine on endometrial explants in vitro. Setting: Prospective study. Patient(s): Thirty-seven eumenorrheic women. Intervention(s): Endometrial samples were obtained with Pipelle suction curette after women signed institutional informed consent forms. Main Outcome Measure(s): DNA fragmentation (TUNEL), immunohistochemistry, and reverse transcription polymerase chain reaction. Result(s): Apoptosis was detected in mid and late secretory endometria. L-arginine induced an increase in apoptosis in stroma (threefold), glands (eightfold), and surface epithelia (fourfold) in proliferative but not secretory endometria explants. Immunostaining of Bcl-2 was almost absent in the secretory endometria, whereas Bax increased in the stroma at the end of the menstrual cycle, coincident to the decrease in the bcl-2/bax mRNA relative ratio (P<.05) observed in secretory endometria. Conclusion(s): The induction of DNA fragmentation by L-arginine on proliferative endometria suggests that NO may be involved in the endometrial apoptotic process, whose control may be related predominantly to the changes of Bcl-2 expression. (C) 2002 by American Society for Reproductive Medicine.