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TRAIL pathway components and their putative role in granulosa cell apoptosis in the human ovary

M Jääskeläinen1, A Kyrönlahti, M Anttonen

  • 1Department of Obstetrics and Gynecology, University of Oulu, P.O. Box 5000, FIN-90014, Oulu, Finland.

Differentiation; Research in Biological Diversity
|March 14, 2009
PubMed

Insights

The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) pathway is involved in regulating oocyte apoptosis during human fetal ovarian development. TRAIL and its receptors are expressed in fetal and adult ovaries, suggesting a role in programmed cell death.

Area of Science:

  • Reproductive Biology
  • Cell Death Mechanisms
  • Developmental Biology

Background:

  • Extensive oocyte apoptosis occurs during fetal ovarian development, but regulatory pathways are poorly understood.
  • Programmed cell death is crucial for selecting viable oocytes and maintaining ovarian function.

Purpose of the Study:

  • To investigate the role of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptors in human fetal and adult ovarian apoptosis.
  • To examine the expression and localization of TRAIL pathway components (TRAIL, TRAIL-R1/DR4, TRAIL-R2/DR5, TRAIL-R3/DcR1, TRAIL-R4/DcR2) in ovarian tissues.

Main Methods:

  • In situ hybridization and immunohistochemistry were used to analyze mRNA and protein expression in human fetal and adult ovarian samples.
  • A human granulosa cell tumor-derived cell line (KGN) was utilized to assess the functional effects of TRAIL on apoptosis.

Main Results:

  • TRAIL, pro-apoptotic TRAIL-R2/DR5, and anti-apoptotic TRAIL-R4/DcR2 were expressed in human fetal ovaries from week 11, with increasing expression towards term, primarily in oocytes.
  • Adult ovaries showed expression of TRAIL, TRAIL-R2/DR5, TRAIL-R3/DcR1, and TRAIL-R4/DcR2 in granulosa and theca cells of developing follicles.
  • TRAIL induced dose-dependent apoptosis in KGN cells, which was inhibited by a caspase inhibitor.

Conclusions:

  • The TRAIL pathway components are expressed in human ovaries during fetal development and in adult follicles.
  • These findings suggest a role for the TRAIL pathway in regulating granulosa cell apoptosis in vitro and potentially in vivo ovarian apoptosis.

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