title: Oocyte-expressed interleukin 7 suppresses granulosa cell apoptosis and promotes oocyte maturation in rats.
abstract: Development of ovarian follicles is regulated by pituitary-derived gonadotropins together with local ovarian paracrine factors. Based on DNA microarray data, we performed RT-PCR and immunostaining to demonstrate the expression of interleukin 7 transcripts in oocytes of preantral, antral, and preovulatory follicles in rats. We also found the expression of interleukin 7 receptor and the coreceptor interleukin 2 receptor gamma in granulosa cells, cumulus cells, and preovulatory oocytes. In cultured rat granulosa cells obtained from early antral and preovulatory follicles, treatment with interleukin 7 stimulated the phosphorylation of AKT, glycogen synthase kinase (GSK3B), and STAT5 proteins in a time- and dose-dependent manner. Furthermore, measurement of mitochondrial reductase activity indicated that treatment with interleukin 7, similar to gonadotropins, increased the number of viable granulosa cells during a 24-h culture period. Furthermore, monitoring of the activities of apoptotic enzymes (caspase 3/7) indicated that treatment with interleukin 7 suppressed apoptosis of cultured granulosa cells from both antral and preovulatory follicles following serum withdrawal. The apoptosis-suppressing actions of interleukin 7 were blocked by an inhibitor of the phosphoinositol-3-kinase (PIK3)/AKT pathway. Furthermore, treatment of cultured preovulatory follicles with interleukin 7, like treatment with human chorionic gonadotropin, induced germinal vesicle breakdown of oocytes. The stimulatory effect of interleukin 7 was also blocked by inhibitors of the PIK3/AKT pathway. The present findings suggest that oocyte-derived interleukin 7 could act on neighboring granulosa cells as a survival factor and promote the nuclear maturation of preovulatory oocytes through activation of the PIK3/AKT pathway.
authors.affiliation: Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Cheng
authors.forename: Ai
authors.initials: A
authors.lastname: Yata
authors.forename: Cynthia
authors.initials: C
authors.lastname: Klein
authors.forename: Joon-Ho
authors.initials: JH
authors.lastname: Cho
authors.forename: Masashi
authors.initials: M
authors.lastname: Deguchi
authors.forename: Aaron J W
authors.initials: AJ
authors.lastname: Hsueh
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D005260:Female; D015870:Gene Expression; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006107:Granulosa Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics; D015851:Interleukin-7 / Q000235:genetics* / Q000494:pharmacology / Q000502:physiology*; D009865:Oocytes / Q000187:drug effects / Q000254:growth & development* / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020395:Receptors, Interleukin-7 / Q000235:genetics; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D017931:DNA Primers; D053631:Interleukin Receptor Common gamma Subunit; D015851:Interleukin-7; D020395:Receptors, Interleukin-7; D050799:STAT5 Transcription Factor; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3