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.


METHODS
Expression of bcl-2, bax, NO synthases (NOS), and the apoptotic effect of L-arginine on endometrial explants in vitro.


METHODS
Prospective study.


METHODS
Thirty-seven eumenorrheic women.


METHODS
Endometrial samples were obtained with Pipelle suction curette after women signed institutional informed consent forms.


METHODS
DNA fragmentation (TUNEL), immunohistochemistry, and reverse transcription polymerase chain reaction.


RESULTS
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.


CONCLUSIONS
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.
Castro
Andrea
A
Institute of Maternal and Child Research, School of Medicine, University of Chile, Santiago, Chile.
Johnson
María Cecilia
MC
Anido
Mabel
M
Cortinez
Armando
A
Gabler
Fernando
F
Vega
Margarita
M
D000328:Adult; D000704:Analysis of Variance; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D004717:Endometrium / Q000166:cytology / Q000502:physiology*; D005260:Female; D019254:Genes, bcl-2; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D005810:Multigene Family; D009569:Nitric Oxide / Q000502:physiology*; D009924:Organ Culture Techniques; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D009569:Nitric Oxide