Register      Login
Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
RESEARCH ARTICLE

Mitochondrial SIRT5 is present in follicular cells and is altered by reduced ovarian reserve and advanced maternal age

Leanne Pacella-Ince A B , Deirdre L. Zander-Fox A B and Michelle Lane A B C
+ Author Affiliations
- Author Affiliations

A University of Adelaide, Medical School South, Level 3. Frome Rd, Adelaide, SA 5000, Australia.

B Repromed, 180 Fullarton Rd, Dulwich, SA 5065, Australia.

C Corresponding author. Email: michelle.lane@adelaide.edu.au

Reproduction, Fertility and Development 26(8) 1072-1083 https://doi.org/10.1071/RD13178
Submitted: 7 June 2013  Accepted: 17 July 2013   Published: 27 August 2013

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.

Additional keywords: AMH, ammonium, CPS1, fertility, IVF, sirtuin 5.


References

Alviggi, C., Humaidan, P., Howles, C. M., Tredway, D., and Hillier, S. G. (2009). Biological versus chronological ovarian age: implications for assisted reproductive technology. Reprod. Biol. Endocrinol. 7, 101.
Biological versus chronological ovarian age: implications for assisted reproductive technology.Crossref | GoogleScholarGoogle Scholar | 19772632PubMed |

Anderson, K. A., and Hirschey, M. D. (2012). Mitochondrial protein acetylation regulates metabolism. Essays Biochem. 52, 23–35.
| 1:CAS:528:DC%2BC38Xht1ShurrM&md5=0336a350f549a9d6e118508f39024b35CAS | 22708561PubMed |

Bagger, P. V., Byskov, A. G., and Christiansen, M. D. (1987). Maturation of mouse oocytes in vitro is influenced by alkalization during their isolation. J. Reprod. Fertil. 80, 251–255.
Maturation of mouse oocytes in vitro is influenced by alkalization during their isolation.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL2s3lsVShtQ%3D%3D&md5=1ddbf21a237535931a5a69c6ae7367c7CAS | 3598961PubMed |

Barneda-Zahonero, B., and Parra, M. (2012). Histone deacetylases and cancer. Mol. Oncol. 6, 579–589.
Histone deacetylases and cancer.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xhs12gt7%2FK&md5=860059364a3fc3e358b02c12af8b1bc7CAS | 22963873PubMed |

Blanchard, T., Ferguson, J., Love, L., Takeda, T., Henderson, B., Hasler, J., and Chalupa, W. (1990). Effect of dietary crude-protein type on fertilization and embryo quality in dairy cattle. Am. J. Vet. Res. 51, 905–908.
| 1:STN:280:DyaK3czhsVSmsA%3D%3D&md5=b5f6ddedcc8d6d61404c5d60d95d41f4CAS | 2368946PubMed |

Brodin, T., Hadziosmanovic, N., Berglund, L., Olovsson, M., and Holte, J. (2013). Antimullerian hormone levels are strongly associated with live-birth rates after assisted reproduction. J. Clin. Endocrinol. Metab. 98, 1107–1114.
Antimullerian hormone levels are strongly associated with live-birth rates after assisted reproduction.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXksFymurY%3D&md5=fb42003e62bd9c123f0105db1f2d31f1CAS | 23408576PubMed |

Canipari, R. (2000). Oocyte–granulosa cell interactions. Hum. Reprod. Update 6, 279–289.
Oocyte–granulosa cell interactions.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD3cvotFKqtA%3D%3D&md5=130a055a83482be900ec1260d30460d8CAS | 10874573PubMed |

Dale, B., Menezo, Y., Cohen, J., DiMatteo, L., and Wilding, M. (1998). Intracellular pH regulation in the human oocyte. Hum. Reprod. 13, 964–970.
Intracellular pH regulation in the human oocyte.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXjs12gurw%3D&md5=0aaf053ae0dee0d2634f2497d3dc7ce7CAS | 9619555PubMed |

Du, J., Zhou, Y., Su, X., Yu, J. J., Khan, S., Jiang, H., Kim, J., Woo, J., Kim, J. H., Choi, B. H., He, B., Chen, W., Zhang, S., Cerione, R. A., Auwerx, J., Hao, Q., and Lin, H. (2011). Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase. Science 334, 806–809.
Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhsVagtrnI&md5=3ca48f9fca0b88acfec12b8dec3a5042CAS | 22076378PubMed |

Eichenlaub-Ritter, U., Vogt, E., Yin, H., and Gosden, R. (2004). Spindles, mitochondria and redox potential in ageing oocytes. Reprod. Biomed. Online 8, 45–58.
Spindles, mitochondria and redox potential in ageing oocytes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXht1Ojsb0%3D&md5=221848afbec62dc0151b955ceb24d60aCAS | 14759287PubMed |

Eppig, J. J. (2001). Oocyte control of ovarian follicular development and function in mammals. Reproduction 122, 829–838.
Oocyte control of ovarian follicular development and function in mammals.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XhvVWjsw%3D%3D&md5=ec70e9109e26ec24fd1da9fdc5425372CAS | 11732978PubMed |

Eppig, J. J., Chesnel, F., Hirao, Y., O’Brien, M. J., Pendola, F. L., Watanabe, S., and Wigglesworth, K. (1997). Oocyte control of granulosa cell development: how and why. Hum. Reprod. 12, 127–132.
| 1:STN:280:DyaK1c%2FpsVSmug%3D%3D&md5=321492613500f0c955c9abe7ab381950CAS | 9433969PubMed |

ESHRE Capri Workshop Group (2005). Fertility and ageing. Hum. Reprod. Update 11, 261–276.
Fertility and ageing.Crossref | GoogleScholarGoogle Scholar | 15831503PubMed |

Ferrari, A., Fiorino, E., Giudici, M., Gilardi, F., Galmozzi, A., Mitro, N., Cermenati, G., Godio, C., Caruso, D., De Fabiani, E., and Crestani, M. (2012). Linking epigenetics to lipid metabolism: focus on histone deacetylases. Mol. Membr. Biol. 29, 257–266.
Linking epigenetics to lipid metabolism: focus on histone deacetylases.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhsFKgs77K&md5=4552219511e8eaaa90f206f611d29850CAS | 23095054PubMed |

Gallinari, P., Di Marco, S., Jones, P., Pallaoro, M., and Steinkuhler, C. (2007). HDACs, histone deacetylation and gene transcription: from molecular biology to cancer therapeutics. Cell Res. 17, 195–211.
| 1:CAS:528:DC%2BD2sXivVSmur0%3D&md5=d3a385ea43457331a1bd3617397e4835CAS | 17325692PubMed |

Gardner, D. K., and Lane, M. (1993). Amino acids and ammonium regulate mouse embryo development in culture. Biol. Reprod. 48, 377–385.
Amino acids and ammonium regulate mouse embryo development in culture.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3sXpvVOrtg%3D%3D&md5=6191fa74a670ec9556ac9cad80f04ed6CAS | 8439627PubMed |

Geng, Y. Q., Li, T. T., Liu, X. Y., Li, Z. H., and Fu, Y. C. (2011). SIRT1 and SIRT5 activity expression and behavioural responses to calorie restriction. J. Cell. Biochem. 112, 3755–3761.
SIRT1 and SIRT5 activity expression and behavioural responses to calorie restriction.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhtlGgurjM&md5=0a0b2c92543dc44f8f80bfaff227072cCAS | 21826711PubMed |

Goud, P. T., Goud, A. P., Qian, C., Laverge, H., Van der Elst, J., De Sutter, P., and Dhont, M. (1998). In vitro maturation of human germinal vesicle stage oocytes: role of cumulus cells and epidermal growth factor in the culture medium. Hum. Reprod. 13, 1638–1644.
In vitro maturation of human germinal vesicle stage oocytes: role of cumulus cells and epidermal growth factor in the culture medium.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXkslOlurY%3D&md5=009aa9d42bcf764665aab458104a7d97CAS | 9688405PubMed |

Greenseid, K., Jindal, S., Zapantis, A., Nihsen, M., Hurwitz, J., and Pal, L. (2009). Declining ovarian reserve adversely influences granulosa cell viability. Fertil. Steril. 91, 2611–2615.
Declining ovarian reserve adversely influences granulosa cell viability.Crossref | GoogleScholarGoogle Scholar | 18565514PubMed |

Grøndahl, M. L., Yding Andersen, C., Bogstad, J., Nielsen, F. C., Meinertz, H., and Borup, R. (2010). Gene expression profiles of single human mature oocytes in relation to age. Hum. Reprod. 25, 957–968.
Gene expression profiles of single human mature oocytes in relation to age.Crossref | GoogleScholarGoogle Scholar | 20147335PubMed |

Haigis, M. C., and Guarente, L. P. (2006). Mammalian sirtuins – emerging roles in physiology, aging and calorie restriction. Genes Dev. 20, 2913–2921.
Mammalian sirtuins – emerging roles in physiology, aging and calorie restriction.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XhtFynu7bJ&md5=1c5658ae843c393c1bd6366552e963c6CAS | 17079682PubMed |

Hammon, D. S., Wang, S., and Holyoak, G. R. (2000). Effects of ammonia during different stages of culture on development of in vitro-produced bovine embryos. Anim. Reprod. Sci. 59, 23–30.
Effects of ammonia during different stages of culture on development of in vitro-produced bovine embryos.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXjtVeqtro%3D&md5=2e008cd8dccf710ab3990777cc2ea1e9CAS | 10804273PubMed |

Hattori, Y., Sato, T., Okada, H., Saito, C., and Sugiura-Ogasawara, M. (2013). Comparison of follicular fluid and serum anti-Mullerian hormone levels as predictors of the outcome of assisted reproductive treatment. Eur. J. Obstet. Gynecol. Reprod. Biol. , .
Comparison of follicular fluid and serum anti-Mullerian hormone levels as predictors of the outcome of assisted reproductive treatment.Crossref | GoogleScholarGoogle Scholar | 23622971PubMed |

Hazout, A., Bouchard, P., Seifer, D. B., Aussage, P., Junca, A. M., and Cohen-Bacrie, P. (2004). Serum antimullerian hormone/mullerian-inhibiting substance appears to be a more discriminatory marker of assisted reproductive technology outcome than follicle-stimulating hormone, inhibin B or oestradiol. Fertil. Steril. 82, 1323–1329.
Serum antimullerian hormone/mullerian-inhibiting substance appears to be a more discriminatory marker of assisted reproductive technology outcome than follicle-stimulating hormone, inhibin B or oestradiol.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXhvFOjsbo%3D&md5=05657987db0fb74727f5b02eccd52f4bCAS | 15533354PubMed |

Honnma, H., Baba, T., Sasaki, M., Hashiba, Y., Oguri, H., Fukunaga, T., Endo, T., and Asada, Y. (2013). Serum anti-Mullerian hormone levels affect the rate of ongoing pregnancy after in vitro fertilization. Reprod. Sci. 20, 51–59.
Serum anti-Mullerian hormone levels affect the rate of ongoing pregnancy after in vitro fertilization.Crossref | GoogleScholarGoogle Scholar | 22814098PubMed |

Houtkooper, R. H., Canto, C., Wanders, R. J., and Auwerx, J. (2010). The secret life of NAD+: an old metabolite controlling new metabolic signalling pathways. Endocr. Rev. 31, 194–223.
The secret life of NAD+: an old metabolite controlling new metabolic signalling pathways.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXmtlSgs7w%3D&md5=45ea91eb730ea585d05b091b732520a7CAS | 20007326PubMed |

Jansen, R. P., and de Boer, K. (1998). The bottleneck: mitochondrial imperatives in oogenesis and ovarian follicular fate. Mol. Cell. Endocrinol. 145, 81–88.
The bottleneck: mitochondrial imperatives in oogenesis and ovarian follicular fate.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXnt1eitrY%3D&md5=aebb9309c167553cbc52d3ad37969402CAS | 9922103PubMed |

Katz-Jaffe, M. G., Surrey, E. S., Minjarez, D. A., Gustofson, R. L., Stevens, J. M., and Schoolcraft, W. B. (2013). Association of abnormal ovarian reserve parameters with a higher incidence of aneuploid blastocysts. Obstet. Gynecol. 121, 71–77.
| 23262930PubMed |

Kim, S. C., Sprung, R., Chen, Y., Xu, Y., Ball, H., Pei, J., Cheng, T., Kho, Y., Xiao, H., Xiao, L., Grishin, N. V., White, M., Yang, X. J., and Zhao, Y. (2006). Substrate and functional diversity of lysine acetylation revealed by a proteomics survey. Mol. Cell 23, 607–618.
Substrate and functional diversity of lysine acetylation revealed by a proteomics survey.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28Xpt1Snurk%3D&md5=ae7163e44290105ebd1dab579205a707CAS | 16916647PubMed |

Koch-Nolte, F., Haag, F., Guse, A. H., Lund, F., and Ziegler, M. (2009). Emerging roles of NAD+ and its metabolites in cell signalling. Sci. Signal. 2, mr1.
Emerging roles of NAD+ and its metabolites in cell signalling.Crossref | GoogleScholarGoogle Scholar | 19211509PubMed |

Lane, M., and Gardner, D. K. (1994). Increase in postimplantation development of cultured mouse embryos by amino acids and induction of fetal retardation and exencephaly by ammonium ions. J. Reprod. Fertil. 102, 305–312.
Increase in postimplantation development of cultured mouse embryos by amino acids and induction of fetal retardation and exencephaly by ammonium ions.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2MXjtFynsrs%3D&md5=82227b1f78e7e27f411de6b5d9d72ae5CAS | 7861382PubMed |

Lane, M., and Gardner, D. K. (2003). Ammonium induces aberrant blastocyst differentiation, metabolism, pH regulation, gene expression and subsequently alters fetal development in the mouse. Biol. Reprod. 69, 1109–1117.
Ammonium induces aberrant blastocyst differentiation, metabolism, pH regulation, gene expression and subsequently alters fetal development in the mouse.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXnsV2nsr8%3D&md5=c3fe97f4803900194393a252aeb6c33bCAS | 12773416PubMed |

Legro, R. S., Wong, I. L., Paulson, R. J., Lobo, R. A., and Sauer, M. V. (1995). Recipient’s age does not adversely affect pregnancy outcome after oocyte donation. Am. J. Obstet. Gynecol. 172, 96–100.
Recipient’s age does not adversely affect pregnancy outcome after oocyte donation.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK2M7ltVahtA%3D%3D&md5=57da9cdc21ae852f34a936b2eb3972abCAS | 7847566PubMed |

Lekamge, D. N., Barry, M., Kolo, M., Lane, M., Gilchrist, R. B., and Tremellen, K. P. (2007). Anti-Mullerian hormone as a predictor of IVF outcome. Reprod. Biomed. Online 14, 602–610.
Anti-Mullerian hormone as a predictor of IVF outcome.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXmt1Cmtr0%3D&md5=6baf00d583d0fa84ab9668558303bb21CAS | 17509203PubMed |

Levi, A. J., Raynault, M. F., Bergh, P. A., Drews, M. R., Miller, B. T., and Scott, R. T. (2001). Reproductive outcome in patients with diminished ovarian reserve. Fertil. Steril. 76, 666–669.
Reproductive outcome in patients with diminished ovarian reserve.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD3MrksVGltg%3D%3D&md5=600d7570c9a4b4b1cc5d05f87e275fcdCAS | 11591396PubMed |

Li, H. W., Lee, V. C., Lau, E. Y., Yeung, W. S., Ho, P. C., and Ng, E. H. (2013). Role of baseline antral follicle count and anti-mullerian hormone in prediction of cumulative live birth in the first in vitro fertilisation cycle: a retrospective cohort analysis. PLoS ONE 8, e61095.
| 1:CAS:528:DC%2BC3sXntVKrsro%3D&md5=e571ab461f18320c4d3c1dbd28941d05CAS | 23637787PubMed |

Lin, W. Q., Yao, L. N., Zhang, D. X., Zhang, W., Yang, X. J., and Yu, R. (2013). The predictive value of anti-mullerian hormone on embryo quality, blastocyst development and pregnancy rate following in vitro fertilization–embryo transfer (IVF-ET). J. Assist. Reprod. Genet. 30, 649–655.
The predictive value of anti-mullerian hormone on embryo quality, blastocyst development and pregnancy rate following in vitro fertilization–embryo transfer (IVF-ET).Crossref | GoogleScholarGoogle Scholar | 23504440PubMed |

Livak, K. J., and Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2(–Delta Delta C(T)) Method. Methods 25, 402–408.
Analysis of relative gene expression data using real-time quantitative PCR and the 2(–Delta Delta C(T)) Method.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XhtFelt7s%3D&md5=9cad4ff7133d540452bb50aaaa4ededfCAS | 11846609PubMed |

Lombard, D. B., Alt, F. W., Cheng, H. L., Bunkenborg, J., Streeper, R. S., Mostoslavsky, R., Kim, J., Yancopoulos, G., Valenzuela, D., Murphy, A., Yang, Y., Chen, Y., Hirschey, M. D., Bronson, R. T., Haigis, M., Guarente, L. P., Farese, R. V., Weissman, S., Verdin, E., and Schwer, B. (2007). Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation. Mol. Cell. Biol. 27, 8807–8814.
Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXmt1ChsA%3D%3D&md5=637ccc2ea3bd4a682604f67cb9eea65fCAS | 17923681PubMed |

Mao, Z., Hine, C., Tian, X., Van Meter, M., Au, M., Vaidya, A., Seluanov, A., and Gorbunova, V. (2011). SIRT6 promotes DNA repair under stress by activating PARP1. Science 332, 1443–1446.
SIRT6 promotes DNA repair under stress by activating PARP1.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXntlOltLg%3D&md5=1ff0a61b8f54cb0acc41abe32a114739CAS | 21680843PubMed |

Mao, Z., Tian, X., Van Meter, M., Ke, Z., Gorbunova, V., and Seluanov, A. (2012). Sirtuin 6 (SIRT6) rescues the decline of homologous recombination repair during replicative senescence. Proc. Natl. Acad. Sci. USA 109, 11 800–11 805.
Sirtuin 6 (SIRT6) rescues the decline of homologous recombination repair during replicative senescence.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xht1eqtr%2FL&md5=be50359c7ae42618a5f122f318061f77CAS |

Martínez, A. I., Pérez-Arellano, I., Pekkala, S., Barcelona, B., and Cervera, J. (2010). Genetic, structural and biochemical basis of carbamoyl phosphate synthetase 1 deficiency. Mol. Genet. Metab. 101, 311–323.
Genetic, structural and biochemical basis of carbamoyl phosphate synthetase 1 deficiency.Crossref | GoogleScholarGoogle Scholar | 20800523PubMed |

May-Panloup, P., Ferre-L’Hotellier, V., Moriniere, C., Marcaillou, C., Lemerle, S., Malinge, M. C., Coutolleau, A., Lucas, N., Reynier, P., Descamps, P., and Guardiola, P. (2012). Molecular characterization of corona radiata cells from patients with diminished ovarian reserve using microarray and microfluidic-based gene expression profiling. Hum. Reprod. 27, 829–843.
Molecular characterization of corona radiata cells from patients with diminished ovarian reserve using microarray and microfluidic-based gene expression profiling.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xisl2rsLw%3D&md5=fb45370818028490af42a41d7bd9dc14CAS | 22246450PubMed |

McReynolds, S., Dzieciatkowska, M., McCallie, B. R., Mitchell, S. D., Stevens, J., Hansen, K., Schoolcraft, W. B., and Katz-Jaffe, M. G. (2012). Impact of maternal aging on the molecular signature of human cumulus cells. Fertil. Steril. 98, 1574–1580.e5.
Impact of maternal aging on the molecular signature of human cumulus cells.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhtlCiurzO&md5=766582508c9cf66c92ec345c38a2a04eCAS | 22968048PubMed |

Michishita, E., Park, J. Y., Burneskis, J. M., Barrett, J. C., and Horikawa, I. (2005). Evolutionarily conserved and non-conserved cellular localizations and functions of human SIRT proteins. Mol. Biol. Cell 16, 4623–4635.
Evolutionarily conserved and non-conserved cellular localizations and functions of human SIRT proteins.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXhtVygtL%2FP&md5=d5cfbc9f6795ea84a620e8d2086a26bdCAS | 16079181PubMed |

Nagaoka, S. I., Hodges, C. A., Albertini, D. F., and Hunt, P. A. (2011). Oocyte-specific differences in cell-cycle control create an innate susceptibility to meiotic errors. Curr. Biol. 21, 651–657.
Oocyte-specific differences in cell-cycle control create an innate susceptibility to meiotic errors.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXltFyjurs%3D&md5=04a6a04717cab91fe5209ff3a367762aCAS | 21497085PubMed |

Nakagawa, T., Lomb, D. J., Haigis, M. C., and Guarente, L. (2009). SIRT5 deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle. Cell 137, 560–570.
SIRT5 deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXlvFamsL8%3D&md5=95d9e64a04b2a6f9349807914b3a3ab5CAS | 19410549PubMed |

Nakamura, Y., Ogura, M., Tanaka, D., and Inagaki, N. (2008). Localization of mouse mitochondrial SIRT proteins: shift of SIRT3 to nucleus by co-expression with SIRT5. Biochem. Biophys. Res. Commun. 366, 174–179.
Localization of mouse mitochondrial SIRT proteins: shift of SIRT3 to nucleus by co-expression with SIRT5.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhsVOktr7L&md5=8ce2a1a4e949bd8ad4f0d83dd6e25f50CAS | 18054327PubMed |

Navot, D., Drews, M. R., Bergh, P. A., Guzman, I., Karstaedt, A., Scott, R. T., Garrisi, G. J., and Hofmann, G. E. (1994). Age-related decline in female fertility is not due to diminished capacity of the uterus to sustain embryo implantation. Fertil. Steril. 61, 97–101.
| 1:STN:280:DyaK2c7itlyjug%3D%3D&md5=b8648be4e60cd0cabf1e936b483f2c33CAS | 8293851PubMed |

North, B. J., Marshall, B. L., Borra, M. T., Denu, J. M., and Verdin, E. (2003). The human Sir2 orthologue, SIRT2, is an NAD+-dependent tubulin deacetylase. Mol. Cell 11, 437–444.
The human Sir2 orthologue, SIRT2, is an NAD+-dependent tubulin deacetylase.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXit1Wgs7c%3D&md5=c01ea4fbd4650356113477a910397639CAS | 12620231PubMed |

Pacella, L., Zander-Fox, D.L., Armstrong, D. T., and Lane, M. (2012). Women with reduced ovarian reserve or advanced maternal age have an altered follicular environment. Fertil. Steril. 98, 986–994.e2.
Women with reduced ovarian reserve or advanced maternal age have an altered follicular environment.Crossref | GoogleScholarGoogle Scholar | 22818290PubMed |

Pellestor, F., Andreo, B., Arnal, F., Humeau, C., and Demaille, J. (2003). Maternal aging and chromosomal abnormalities: new data drawn from in vitro unfertilized human oocytes. Hum. Genet. 112, 195–203.
| 12522562PubMed |

Peng, C., Lu, Z., Xie, Z., Cheng, Z., Chen, Y., Tan, M., Luo, H., Zhang, Y., He, W., Yang, K., Zwaans, B.M., Tishkoff, D., Ho, L., Lombard, D., He, T.C., Dai, J., Verdin, E., Ye, Y., and Zhao, Y. (2011a). The first identification of lysine malonylation substrates and its regulatory enzyme. Mol. Cell. Proteomics 10, M111.012658.
The first identification of lysine malonylation substrates and its regulatory enzyme.Crossref | GoogleScholarGoogle Scholar | 21908771PubMed |

Peng, L., Yuan, Z., Ling, H., Fukasawa, K., Robertson, K., Olashaw, N., Koomen, J., Chen, J., Lane, W. S., and Seto, E. (2011b). SIRT1 deacetylates the DNA methyltransferase 1 (DNMT1) protein and alters its activities. Mol. Cell. Biol. 31, 4720–4734.
SIRT1 deacetylates the DNA methyltransferase 1 (DNMT1) protein and alters its activities.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhsFakt7rO&md5=1abc4bcd8a6c84e4b762333466f80d40CAS | 21947282PubMed |

Piñero-Sagredo, E., Nunes, S., de Los Santos, M. J., Celda, B., and Esteve, V. (2010). NMR metabolic profile of human follicular fluid. NMR Biomed. 23, 485–495.
NMR metabolic profile of human follicular fluid.Crossref | GoogleScholarGoogle Scholar | 20336675PubMed |

Revelli, A., Delle Piane, L., Casano, S., Molinari, E., Massobrio, M., and Rinaudo, P. (2009). Follicular fluid content and oocyte quality: from single biochemical markers to metabolomics. Reprod. Biol. Endocrinol. 7, 40.
Follicular fluid content and oocyte quality: from single biochemical markers to metabolomics.Crossref | GoogleScholarGoogle Scholar | 19413899PubMed |

Rooke, J. A., Ewen, M., Mackie, K., Staines, M. E., McEvoy, T. G., and Sinclair, K. D. (2004). Effect of ammonium chloride on the growth and metabolism of bovine ovarian granulosa cells and the development of ovine oocytes matured in the presence of bovine granulosa cells previously exposed to ammonium chloride. Anim. Reprod. Sci. 84, 53–71.
Effect of ammonium chloride on the growth and metabolism of bovine ovarian granulosa cells and the development of ovine oocytes matured in the presence of bovine granulosa cells previously exposed to ammonium chloride.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXmsVGjsrs%3D&md5=4e4b7163246a8ab1f1365f37df9c637dCAS | 15302387PubMed |

Schlicker, C., Gertz, M., Papatheodorou, P., Kachholz, B., Becker, C. F., and Steegborn, C. (2008). Substrates and regulation mechanisms for the human mitochondrial sirtuins Sirt3 and Sirt5. J. Mol. Biol. 382, 790–801.
Substrates and regulation mechanisms for the human mitochondrial sirtuins Sirt3 and Sirt5.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhtVKisb7I&md5=536a880f0d0bededc556d132899ac182CAS | 18680753PubMed |

Schweigert, F. J., Gericke, B., Wolfram, W., Kaisers, U., and Dudenhausen, J. W. (2006). Peptide and protein profiles in serum and follicular fluid of women undergoing IVF. Hum. Reprod. 21, 2960–2968.
Peptide and protein profiles in serum and follicular fluid of women undergoing IVF.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XhtVynsrzI&md5=b60ff18df57c7eeb413481e09bc7bddfCAS | 16893915PubMed |

Shalgi, R., Kraicer, P. F., and Soferman, N. (1972). Gases and electrolytes of human follicular fluid. J. Reprod. Fertil. 28, 335–340.
Gases and electrolytes of human follicular fluid.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaE387kt1amuw%3D%3D&md5=c54cef15fb7548730c02ef934602923cCAS | 4552284PubMed |

Sinclair, K. D., Kuran, M., Gebbie, F. E., Webb, R., and McEvoy, T. G. (2000). Nitrogen metabolism and fertility in cattle: II. Development of oocytes recovered from heifers offered diets differing in their rate of nitrogen release in the rumen. J. Anim. Sci. 78, 2670–2680.
| 1:CAS:528:DC%2BD3cXnsVarsb0%3D&md5=9d5b1c291f2022d82c3de12a0d1fb79bCAS | 11048933PubMed |

Skiadas, C. C., Duan, S., Correll, M., Rubio, R., Karaca, N., Ginsburg, E. S., Quackenbush, J., and Racowsky, C. (2012). Ovarian reserve status in young women is associated with altered gene expression in membrana granulosa cells. Mol. Hum. Reprod. 18, 362–371.
Ovarian reserve status in young women is associated with altered gene expression in membrana granulosa cells.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XpsVahsbg%3D&md5=36c285b85ac3eb4f0ddcc049ef7e4161CAS | 22355044PubMed |

Sugiura, K., Pendola, F. L., and Eppig, J. J. (2005). Oocyte control of metabolic co-operativity between oocytes and companion granulosa cells: energy metabolism. Dev. Biol. 279, 20–30.
Oocyte control of metabolic co-operativity between oocytes and companion granulosa cells: energy metabolism.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXhtlemtb4%3D&md5=8d0ae004906415fd4328ac872f34117fCAS | 15708555PubMed |

Tremellen, K., and Kolo, M. (2010). Serum anti-Mullerian hormone is a useful measure of quantitative ovarian reserve but does not predict the chances of live-birth pregnancy. Aust. N. Z. J. Obstet. Gynaecol. 50, 568–572.
Serum anti-Mullerian hormone is a useful measure of quantitative ovarian reserve but does not predict the chances of live-birth pregnancy.Crossref | GoogleScholarGoogle Scholar | 21133869PubMed |

Virant-Klun, I., Tomazevic, T., Vrtacnik-Bokal, E., Vogler, A., Krsnik, M., and Meden-Vrtovec, H. (2006). Increased ammonium in culture medium reduces the development of human embryos to the blastocyst stage. Fertil. Steril. 85, 526–528.
Increased ammonium in culture medium reduces the development of human embryos to the blastocyst stage.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28Xit12it78%3D&md5=0ac89057731d8ba6abec11e0abf43ca7CAS | 16595249PubMed |

Wang, R. H., Sengupta, K., Li, C., Kim, H. S., Cao, L., Xiao, C., Kim, S., Xu, X., Zheng, Y., Chilton, B., Jia, R., Zheng, Z. M., Appella, E., Wang, X. W., Ried, T., and Deng, C. X. (2008). Impaired DNA damage response, genome instability and tumourigenesis in SIRT1 mutant mice. Cancer Cell 14, 312–323.
Impaired DNA damage response, genome instability and tumourigenesis in SIRT1 mutant mice.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXht1GlsL3F&md5=b2d36b844a5d1a51546a666f9894292cCAS | 18835033PubMed |

Wunder, D. M., Guibourdenche, J., Birkhauser, M. H., and Bersinger, N. A. (2008). Anti-Mullerian hormone and inhibin B as predictors of pregnancy after treatment by in vitro fertilization/intracytoplasmic sperm injection. Fertil. Steril. 90, 2203–2210.
Anti-Mullerian hormone and inhibin B as predictors of pregnancy after treatment by in vitro fertilization/intracytoplasmic sperm injection.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXmtlOqtQ%3D%3D&md5=b52a46a6671c8fa528cde9e5c3d69d96CAS | 18291376PubMed |

Yuan, Y., and Krisher, R. L. (2010). Effect of ammonium during in vitro maturation on oocyte nuclear maturation and subsequent embryonic development in pigs. Anim. Reprod. Sci. 117, 302–307.
Effect of ammonium during in vitro maturation on oocyte nuclear maturation and subsequent embryonic development in pigs.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhsVGltrbJ&md5=1b6cee8d00fabfb13c5b653af77605e6CAS | 19539436PubMed |

Zander, D. L., Thompson, J. G., and Lane, M. (2006). Perturbations in mouse embryo development and viability caused by ammonium are more severe after exposure at the cleavage stages. Biol. Reprod. 74, 288–294.
Perturbations in mouse embryo development and viability caused by ammonium are more severe after exposure at the cleavage stages.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28Xot1KlsA%3D%3D&md5=af3ab2bb18e365955188861d2f1b7d0cCAS | 16221986PubMed |

Zhang, Z., Tan, M., Xie, Z., Dai, L., Chen, Y., and Zhao, Y. (2011). Identification of lysine succinylation as a new post-translational modification. Nat. Chem. Biol. 7, 58–63.
Identification of lysine succinylation as a new post-translational modification.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhsFGgtrfM&md5=fbae20fe9d7057df60194fbeaa56358eCAS | 21151122PubMed |

Ziegler, M. (2000). New functions of a long-known molecule. Emerging roles of NAD in cellular signalling. Eur. J. Biochem. 267, 1550–1564.
New functions of a long-known molecule. Emerging roles of NAD in cellular signalling.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXit1arsrk%3D&md5=167c84a7559079a3a8f3f1a3ffa24a2eCAS | 10712584PubMed |