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

Fertil Steril. 2002 Sep;78(3):587-95. doi: 10.1016/s0015-0282(02)03304-6.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analysis of Variance
  • Apoptosis / genetics
  • Apoptosis / physiology*
  • Endometrium / cytology
  • Endometrium / physiology*
  • Female
  • Genes, bcl-2*
  • Humans
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Multigene Family
  • Nitric Oxide / physiology*
  • Organ Culture Techniques
  • Proto-Oncogene Proteins / physiology*
  • Proto-Oncogene Proteins c-bcl-2*
  • Reference Values
  • Reverse Transcriptase Polymerase Chain Reaction
  • bcl-2-Associated X Protein

Substances

  • BAX protein, human
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • Nitric Oxide