title: Mitochondrial SIRT5 is present in follicular cells and is altered by reduced ovarian reserve and advanced maternal age.
abstract: Women with reduced ovarian reserve or advanced maternal age have an altered metabolic follicular microenvironment. As sirtuin 5 (SIRT5) senses cellular metabolic state and post-translationally alters protein function, its activity may directly impact on oocyte viability and pregnancy outcome. Therefore, we investigated the role of SIRT5 in relation to ovarian reserve and maternal age. Women (n=47) undergoing routine IVF treatment were recruited and allocated to one of three cohorts based on ovarian reserve and maternal age. Surplus follicular fluid, granulosa and cumulus cells were collected. SIRT5 mRNA, protein and protein activity was confirmed in granulosa and cumulus cells via qPCR, immunohistochemistry, western blotting and desuccinylation activity. The presence of carbamoyl phosphate synthase I (CPS1), a target of SIRT5, was investigated by immunohistochemistry and follicular-fluid ammonium concentrations determined via microfluorometry. Women with reduced ovarian reserve or advanced maternal age had decreased SIRT5 mRNA, protein and desuccinylation activity in granulosa and cumulus cells resulting in an accumulation of follicular-fluid ammonium, presumably via alterations in activity of a SIRT5 target, CPS1, which was present in granulosa and cumulus cells. This suggests a role for SIRT5 in influencing oocyte quality and IVF outcomes.
authors: University of Adelaide, Medical School South, Level 3. Frome Rd, Adelaide, SA 5000, Australia.
authors: Leanne
authors: L
authors: Pacella-Ince
authors: University of Adelaide, Medical School South, Level 3. Frome Rd, Adelaide, SA 5000, Australia.
authors: Deirdre L
authors: DL
authors: Zander-Fox
authors: University of Adelaide, Medical School South, Level 3. Frome Rd, Adelaide, SA 5000, Australia.
authors: Michelle
authors: M
authors: Lane
mesh_terms: D000328:Adult; D064751:Ammonium Compounds / Q000378:metabolism; D002222:Carbamoyl-Phosphate Synthase (Ammonia) / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D005307:Fertilization in Vitro; D015571:Follicular Fluid / Q000201:enzymology; D006107:Granulosa Cells / Q000201:enzymology*; D006801:Humans; D007247:Infertility, Female / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D008423:Maternal Age; D008928:Mitochondria / Q000201:enzymology*; D065851:Ovarian Reserve; D011247:Pregnancy; D018873:Pregnancy Rate; D012333:RNA, Messenger / Q000378:metabolism; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D064751:Ammonium Compounds; D012333:RNA, Messenger; C508544:SIRT5 protein, human; D037761:Sirtuins; D002222:Carbamoyl-Phosphate Synthase (Ammonia)