The role of interleukin-6 in the regulation of granulosa cell apoptosis during follicular atresia in pig ovaries

• Published in: Journal of Reproduction and Development Vol. 53; no. 3; pp. 481 - 490
• Main Authors: Maeda, A.(Tokyo Univ. (Japan)), Inoue, N, Matsuda Minehata, F, Goto, Y, Cheng, Y, Manabe, N
• Format: Journal Article
• Language: English
• Published: Japan THE SOCIETY FOR REPRODUCTION AND DEVELOPMENT 01.06.2007
• Subjects: Animals; APOPTOSE; APOPTOSIS; Apoptosis - physiology; Base Sequence; CASP8 and FADD-Like Apoptosis Regulating Protein - metabolism; Cell Line; CELLULE DE LA GRANULOSA; CELULAS DE LA GRANULOSA; CERDAS; CITOQUINAS; CYTOKINE; CYTOKINES; ELISA; Female; FOLICULOS OVARICOS; Follicular atresia; Follicular Atresia - metabolism; Follicular Atresia - physiology; Follicular Fluid - metabolism; FOLLICULE OVARIEN; Granulosa cell; GRANULOSA CELLS; Granulosa Cells - metabolism; Granulosa Cells - physiology; Humans; In Situ Nick-End Labeling; Interleukin-6 (IL-6); Interleukin-6 - metabolism; Interleukin-6 - physiology; INTERLEUKINE; INTERLEUKINS; INTERLEUQUINAS; Macrophages - physiology; Molecular Sequence Data; OVAIRE; OVARIAN FOLLICLES; OVARIES; OVARIOS; Ovary - immunology; PCR; Pig ovary; Proliferating Cell Nuclear Antigen - metabolism; RNA, Messenger - metabolism; SOWS; Swine; TEST ELISA; TRUIE
• ISSN: 0916-8818; 1348-4400
• DOI: 10.1262/jrd.18149

More than 99% of follicles in mammalian ovaries undergo a degenerative process known as atresia, and only a few follicles actually ovulate during follicular growth and development. Follicular selection mostly depends on granulosa cell apoptosis, but the molecular mechanism behind the regulation of this selective atresia is still largely unknown. In the present study, to examine whether or not interleukin-6 (IL-6), a multifunctional cytokine, is involved in apoptosis during atresia in pig ovaries, the expression of IL-6 mRNA in granulosa cells was quantified by real-time reverse transcription-polymerase chain reaction (RT-PCR). The level of mRNA decreased during atresia. Enzyme-linked immunosorbent assay (ELISA) showed that the level of IL-6 protein in follicular fluid also decreased during atresia. Moreover, recombinant human IL-6 upregulated the expression of an intracellular apoptosis inhibitor, cellular FLICE-like inhibitory protein long form (cFLIPsub(L)), in cultured cells derived from human granulosa cells. It is possible that IL-6 is produced in the granulosa cells of healthy follicles, that it increases the cFLIPsub(L) level, and cFLIPsub(L) then prevents apoptotic cell death.