Analysis of apoptosis and expression of bcl-2 gene family members in the human and baboon ovary

Koji Kugu, Valerie S. Ratts, Gary N. Piquette, Kim I. Tilly, Xiao Jing Tao, Stephanie Martimbeau, Graham W. Aberdeen, Stanislaw Krajewski, John C. Reed, Gerald J. Pepe, Eugene D. Albrecht, Jonathan L. Tilly

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110 Scopus citations


Recent data support a role for apoptosis, under tight regulatory control by bcl-2, oxidative stress response, tumor suppressor, and GASP gene family members, in mediating granulosa cell demise during follicular atresia in the rodent and avian ovary. Herein we evaluated the occurrence of apoptosis in the human and baboon ovary relative to follicular health status, and analyzed expression of several cell death genes in these tissues. In situ localization of DNA strand breaks in fixed human and baboon ovarian tissue sections indicated that apoptosis was essentially restricted to granulosa cells of atretic antral follicles. Biochemical analysis of DNA oligonucleosomes in individual follicles isolated from baboon ovaries during the ovulatory phase revealed the presence of apoptotic DNA fragments in subordinate but not dominant follicles, thus substantiating the in situ labeling studies. Messenger RNA transcripts encoded by the bar death susceptibility gene, the bcl-x(long) survival gene, the bcl-x(short) pro-apoptosis gene, the p53 tumor suppressor gene, and two members of the GASP gene family (CASP-2/Ich-1, CASP-3/ CPP32), were detected by Northern blot analysis of total RNA prepared either from human ovaries or from Percoll-purified granulosa-lutein cells obtained from patients undergoing assisted reproductive technologies. Lastly, immunohistochemical localization of the BAX death-susceptibility protein in the human ovary revealed abundant expression in granulosa cells of early atretic follicles, whereas BAX protein was extremely low or non-detectable in healthy or grossly-atretic follicles. We conclude that apoptosis occurs during, and is probably responsible for, folicular atresia in the human and baboon ovary. Moreover, apoptosis in the human ovary is likely controlled by altered expression of the same cohort of cell death regulatory factors recently implicated as primary determinants of apoptosis induction or suppression in the rodent ovary.

Original languageEnglish
Pages (from-to)67-76
Number of pages10
JournalCell Death and Differentiation
Issue number1
StatePublished - Jan 1998


  • Apoptosis
  • Atresia
  • BAX
  • BCL-2
  • BCL-X
  • CPP32
  • Caspase
  • Granulosa cell
  • ICH-1
  • Ovary
  • P53


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