Antioxidant supplementation during in vitro culture improves mitochondrial function and development of embryos from aged female mice
Elena Silva A C , Alison F. Greene A , Kevin Strauss A , Jason R. Herrick A , William B. Schoolcraft B and Rebecca L. Krisher A
+ Author Affiliations
- Author Affiliations
A National Foundation for Fertility Research, 10290 RidgeGate Cr., Lone Tree, CO 80124, USA.
B Colorado Center for Reproductive Medicine, 10290 RidgeGate Cr., Lone Tree, CO 80124, USA.
C Corresponding author. Email: esilva@fertilityresearch.org
Reproduction, Fertility and Development 27(6) 975-983 https://doi.org/10.1071/RD14474
Submitted: 28 November 2014 Accepted: 20 January 2015 Published: 5 March 2015
Abstract
Maternal aging results in reduced oocyte and blastocyst quality, thought to be due, in part, to mitochondrial dysfunction and accumulation of reactive oxygen species. To reduce oxidative stress, the antioxidants α-lipoic acid (ALA; 10 µM), α-tocopherol (250 µM), hypotaurine (1 mM) and N-acetylcysteine (NAC; 1 mM), and sirtuin (100 ng mL–1) were added to embryo culture medium (AntiOX) and compared with a control (CON) without antioxidants to assess blastocyst development after in vitro maturation and fertilisation of oocytes from aged B6D2F1 female mice (13.5 months). Development to the blastocyst stage increased in the AntiOX compared with CON group (87.6% vs 72.7%, respectively; P < 0.01), in addition to higher mitochondrial membrane potential and ATP levels in the AntiOX group. Expression of genes associated with oxidative stress (PI3K, FOXO3A and GLRX2) was upregulated in the CON compared with AntiOX group. In addition to AntiOX, a medium containing only NAC and ALA (rAntiOX) was used to culture embryos from young CF1 females (6–8 weeks). More blastocysts developed in the rAntiOX compared with CON group (64.1% vs 43.3%, respectively; P < 0.01), although AntiOX (48.0% blastocysts) did not result in improved development in young mice. Antioxidants improved mitochondrial activity, gene expression and development in embryos of older female mice, whereas a reduced level of antioxidants during culture was beneficial to embryos from young mice.
Additional keywords: culture medium, oocyte, oxidative stress.
References
Acton, B. M., Jurisicova, A., Jurisica, I., and Casper, R. F. (2004). Alterations in mitochondrial membrane potential during preimplantation stages of mouse and human embryo development. Mol. Hum. Reprod. 10, 23–32.| Alterations in mitochondrial membrane potential during preimplantation stages of mouse and human embryo development.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXpvVeltro%3D&md5=380942d842e6841b28834eb58907f54aCAS | 14665703PubMed |
Bakhtari, A., and Ross, P. J. (2014). DPPA3 prevents cytosine hydroxymethylation of the maternal pronucleus and is required for normal development in bovine embryos. Epigenetics 9, 1271–1279.
| DPPA3 prevents cytosine hydroxymethylation of the maternal pronucleus and is required for normal development in bovine embryos.Crossref | GoogleScholarGoogle Scholar | 25147917PubMed |
Barnett, D. K., and Bavister, B. D. (1992). Hypotaurine requirement for in vitro development of golden hamster one-cell embryos into morulae and blastocysts, and production of term offspring from in vitro-fertilized ova. Biol. Reprod. 47, 297–304.
| Hypotaurine requirement for in vitro development of golden hamster one-cell embryos into morulae and blastocysts, and production of term offspring from in vitro-fertilized ova.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK38XltVyqur4%3D&md5=547c3ecb9a9f55d176272bca5d1459aeCAS | 1391335PubMed |
Bartmann, A. K., Romao, G. S., Ramos Eda, S., and Ferriani, R. A. (2004). Why do older women have poor implantation rates? A possible role of the mitochondria. J. Assist. Reprod. Genet. 21, 79–83.
| Why do older women have poor implantation rates? A possible role of the mitochondria.Crossref | GoogleScholarGoogle Scholar | 15202735PubMed |
Benkhalifa, M., Ferreira, Y. J., Chahine, H., Louanjli, N., Miron, P., Merviel, P., and Copin, H. (2014). Mitochondria: participation to infertility as source of energy and cause of senescence. Int. J. Biochem. Cell Biol. 55, 60–64.
| Mitochondria: participation to infertility as source of energy and cause of senescence.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXhsVaktrjE&md5=524d4dd72d3dacee77bfabd12fba9116CAS | 25150832PubMed |
Bentov, Y., Esfandiari, N., Burstein, E., and Casper, R. F. (2010). The use of mitochondrial nutrients to improve the outcome of infertility treatment in older patients. Fertil. Steril. 93, 272–275.
| The use of mitochondrial nutrients to improve the outcome of infertility treatment in older patients.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXit1Wmt7c%3D&md5=25dd6af24a88d1ed7c5149e76b398442CAS | 19732879PubMed |
Centers for Disease Control and Prevention, American Society for Reproductive Medicine, Society for Assisted Reproductive Technology (2013). ‘2011 Assisted Reproductive Technology National Summary Report.’ (US Department of Health and Human Services: Atlanta.)
Chappel, S. (2013). The role of mitochondria from mature oocyte to viable blastocyst. Obstet. Gynecol. Int. 2013, 183024.
| The role of mitochondria from mature oocyte to viable blastocyst.Crossref | GoogleScholarGoogle Scholar | 23766762PubMed |
Di Emidio, G., Falone, S., Vitti, M., D’Alessandro, A. M., Vento, M., Di Pietro, C., Amicarelli, F., and Tatone, C. (2014). SIRT1 signalling protects mouse oocytes against oxidative stress and is deregulated during aging. Hum. Reprod. 29, 2006–2017.
| SIRT1 signalling protects mouse oocytes against oxidative stress and is deregulated during aging.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXhtl2gtbzN&md5=0d581b37f6e3ca90db5db2d1d7c239eaCAS | 24963165PubMed |
Dumollard, R., Duchen, M., and Carroll, J. (2007). The role of mitochondrial function in the oocyte and embryo. Curr. Top. Dev. Biol. 77, 21–49.
| The role of mitochondrial function in the oocyte and embryo.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXmt1Gltb4%3D&md5=ef902ce04a34ede18ce030f99570900eCAS | 17222699PubMed |
Dumollard, R., Carroll, J., Duchen, M. R., Campbell, K., and Swann, K. (2009). Mitochondrial function and redox state in mammalian embryos. Semin. Cell Dev. Biol. 20, 346–353.
| Mitochondrial function and redox state in mammalian embryos.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXltVCmsLo%3D&md5=8e1436f46bb793d40b3bb0450eec5a94CAS | 19530278PubMed |
Eppig, J. J., and O’Brien, M. (1995). In vitro maturation and fertilization of oocytes isolated from aged mice: a strategy to rescue valuable genetic resources. J. Assist. Reprod. Genet. 12, 269–273.
| In vitro maturation and fertilization of oocytes isolated from aged mice: a strategy to rescue valuable genetic resources.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK28%2FlvFKmuw%3D%3D&md5=56aa89f86ffeca7be138095c08a4601eCAS | 7580024PubMed |
Ferber, E. C., Peck, B., Delpuech, O., Bell, G. P., East, P., and Schulze, A. (2012). FOXO3a regulates reactive oxygen metabolism by inhibiting mitochondrial gene expression. Cell Death Differ. 19, 968–979.
| FOXO3a regulates reactive oxygen metabolism by inhibiting mitochondrial gene expression.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xms1ynurg%3D&md5=c513f23d3995cac187d8af6c66ae42c6CAS | 22139133PubMed |
Finkel, T. (2011). Signal transduction by reactive oxygen species. J. Cell Biol. 194, 7–15.
| Signal transduction by reactive oxygen species.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXptFKnt7k%3D&md5=5ade71c161949a126721ae49a4095e74CAS | 21746850PubMed |
Franasiak, J. M., Forman, E. J., Hong, K.H., Werner, M.D., Upham, K.M., Treff, N.R., and Scott, R.T. (2014). The nature of aneuploidy with increasing age of the female partner: a review of 15,169 consecutive trophectoderm biopsies evaluated with comprehensive chromosomal screening. Fertil. Steril. 101, 656–663 e651.
| The nature of aneuploidy with increasing age of the female partner: a review of 15,169 consecutive trophectoderm biopsies evaluated with comprehensive chromosomal screening.Crossref | GoogleScholarGoogle Scholar | 24355045PubMed |
Herrick, J.R., Strauss, K.J., Schneiderman, A., Rawlins, M., Stevens, J., Schoolcraft, W.B., and Krisher, R.L. (2013). The beneficial effects of reduced magnesium during the oocyte-to-embryo transition are conserved in mice, domestic cats and humans. Reprod. Fertil. Dev. , .
| The beneficial effects of reduced magnesium during the oocyte-to-embryo transition are conserved in mice, domestic cats and humans.Crossref | GoogleScholarGoogle Scholar |
Hosseini, S. M., Forouzanfar, M., Hajian, M., Asgari, V., Abedi, P., Hosseini, L., Ostadhosseini, S., Moulavi, F., Safahani Langrroodi, M., Sadeghi, H., Bahramian, H., Eghbalsaied, S., and Nasr-Esfahani, M. H. (2009). Antioxidant supplementation of culture medium during embryo development and/or after vitrification–warming; which is the most important? J. Assist. Reprod. Genet. 26, 355–364.
| Antioxidant supplementation of culture medium during embryo development and/or after vitrification–warming; which is the most important?Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD1MrmslCgtw%3D%3D&md5=5db734e5c80affab4ab0fb0e88668dbcCAS | 19543824PubMed |
Janny, L., and Menezo, Y. J. (1996). Maternal age effect on early human embryonic development and blastocyst formation. Mol. Reprod. Dev. 45, 31–37.
| Maternal age effect on early human embryonic development and blastocyst formation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK28XlsFOisrg%3D&md5=75bc20d8ae1a704b29d31f4818a89f91CAS | 8873066PubMed |
Kawamura, Y., Uchijima, Y., Horike, N., Tonami, K., Nishiyama, K., Amano, T., Asano, T., Kurihara, Y., and Kurihara, H. (2010). Sirt3 protects in vitro-fertilized mouse preimplantation embryos against oxidative stress-induced p53-mediated developmental arrest. J. Clin. Invest. 120, 2817–2828.
| Sirt3 protects in vitro-fertilized mouse preimplantation embryos against oxidative stress-induced p53-mediated developmental arrest.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhtVaiur7E&md5=caa3db3fc690c65326b72f0441266d03CAS | 20644252PubMed |
Klein, J., and Sauer, M. V. (2001). Assessing fertility in women of advanced reproductive age. Am. J. Obstet. Gynecol. 185, 758–770.
| Assessing fertility in women of advanced reproductive age.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD3MritFKnsA%3D%3D&md5=4ddb4247ece29d4a2fb762c00602ee6dCAS | 11568811PubMed |
Komatsu, K., Iwase, A., Mawatari, M., Wang, J., Yamashita, M., and Kikkawa, F. (2014). Mitochondrial membrane potential in 2-cell stage embryos correlates with the success of preimplantation development. Reproduction 147, 627–638.
| Mitochondrial membrane potential in 2-cell stage embryos correlates with the success of preimplantation development.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXovFGntbY%3D&md5=ca5dec53480da92bf52cabb1cc71241bCAS | 24459207PubMed |
Lim, A. S. T., and Tsakok, M. F. H. (1997). Age-related decline in fertility: A link to degenerative oocytes. Fertil. Steril. 68, 265–271.
| Age-related decline in fertility: A link to degenerative oocytes.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK2szosVGrtA%3D%3D&md5=8c59a4a9947567e811b6394ca49d6621CAS |
Liochev, S. I. (2013). Reactive oxygen species and the free radical theory of aging. Free Radic. Biol. Med. 60, 1–4.
| Reactive oxygen species and the free radical theory of aging.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXnsFSqu7c%3D&md5=4d8f4210ac590b6085ab2a1ccc509b3cCAS | 23434764PubMed |
Liu, J., Liu, M., Ye, X., Liu, K., Huang, J., Wang, L., Ji, G., Liu, N., Tang, X., Baltz, J. M., Keefe, D. L., and Liu, L. (2012). Delay in oocyte aging in mice by the antioxidant N-acetyl-l-cysteine (NAC). Hum. Reprod. 27, 1411–1420.
| Delay in oocyte aging in mice by the antioxidant N-acetyl-l-cysteine (NAC).Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xmt1SltL4%3D&md5=0ea727a0600c0e702284c5f51015a47eCAS | 22357770PubMed |
Lu, Q., Zhai, Y., Cheng, Q., Liu, Y., Gao, X., Zhang, T., Wei, Y., Zhang, F., and Yin, X. (2013). The Akt–FoxO3a–manganese superoxide dismutase pathway is involved in the regulation of oxidative stress in diabetic nephropathy. Exp. Physiol. 98, 934–945.
| The Akt–FoxO3a–manganese superoxide dismutase pathway is involved in the regulation of oxidative stress in diabetic nephropathy.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXnsVCgu70%3D&md5=362f00de45d9926405b06cc80a936827CAS | 23159718PubMed |
Mathews, T. J., and Hamilton, B. E. (2014). ‘First Births to Older Women Continue to Rise. NCHS Data Brief, No. 152.’ (National Center for Health Statistics: Hyattsville, MD.)
McPherson, N. O., Zander-Fox, D., and Lane, M. (2014). Stimulation of mitochondrial embryo metabolism by dichloroacetic acid in an aged mouse model improves embryo development and viability. Fertil. Steril. 101, 1458–1466.
| Stimulation of mitochondrial embryo metabolism by dichloroacetic acid in an aged mouse model improves embryo development and viability.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXivFCgtb4%3D&md5=95a8d2d5219a3a128516594386689b82CAS | 24559721PubMed |
Natarajan, R., Shankar, M. B., and Munuswamy, D. (2010). Effect of alpha-tocopherol supplementation on in vitro maturation of sheep oocytes and in vitro development of preimplantation sheep embryos to the blastocyst stage. J. Assist. Reprod. Genet. 27, 483–490.
| Effect of alpha-tocopherol supplementation on in vitro maturation of sheep oocytes and in vitro development of preimplantation sheep embryos to the blastocyst stage.Crossref | GoogleScholarGoogle Scholar | 20454845PubMed |
Olson, S. E., and Seidel, G. E. (2000). Culture of in vitro-produced bovine embryos with vitamin E improves development in vitro and after transfer to recipients. Biol. Reprod. 62, 248–252.
| Culture of in vitro-produced bovine embryos with vitamin E improves development in vitro and after transfer to recipients.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXotVOktA%3D%3D&md5=e8f94a40454dc652a9cc628a062c50e3CAS | 10642559PubMed |
Paczkowski, M., Silva, E., Schoolcraft, W. B., and Krisher, R. L. (2013). Comparative importance of fatty acid beta-oxidation to nuclear maturation, gene expression, and glucose metabolism in mouse, bovine, and porcine cumulus oocyte complexes. Biol. Reprod. 88, 111.
| Comparative importance of fatty acid beta-oxidation to nuclear maturation, gene expression, and glucose metabolism in mouse, bovine, and porcine cumulus oocyte complexes.Crossref | GoogleScholarGoogle Scholar | 23536372PubMed |
Pfaffl, M. W., Horgan, G. W., and Dempfle, L. (2002). Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res. 30, e36.
| Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR.Crossref | GoogleScholarGoogle Scholar | 11972351PubMed |
Preis, K. A., Seidel, G., and Gardner, D. K. (2005). Metabolic markers of developmental competence for in vitro-matured mouse oocytes. Reproduction 130, 475–483.
| Metabolic markers of developmental competence for in vitro-matured mouse oocytes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXhtFent7rI&md5=fc1396365ce291a49149f2719d1cfef0CAS | 16183865PubMed |
Quinn, P., Kerin, J. F., and Warnes, G. M. (1985). Improved pregnancy rate in human in vitro fertilization with the use of a medium based on the composition of human tubal fluid. Fertil. Steril. 44, 493–498.
| 1:STN:280:DyaL28%2FjtVOnuw%3D%3D&md5=69089f13fe7a313b72f2d4bf688724acCAS | 3902512PubMed |
Rabinowitz, M., Ryan, A., Gemelos, G., Hill, M., Baner, J., Cinnioglu, C., Banjevic, M., Potter, D., Petrov, D. A., and Demko, Z. (2012). Origins and rates of aneuploidy in human blastomeres. Fertil. Steril. 97, 395–401.
| Origins and rates of aneuploidy in human blastomeres.Crossref | GoogleScholarGoogle Scholar | 22195772PubMed |
Rozen, S., and Skaletsky, H. (2000). Primer3 on the WWW for general users and for biologist programmers. Methods Mol. Biol. 132, 365–386.
| 1:CAS:528:DyaK1MXmslKqsbo%3D&md5=210b3fd9b4243645aaae275c22dcda1eCAS | 10547847PubMed |
Sauer, M. V., Paulson, R. J., Ary, B. A., and Lobo, R. A. (1994). Three hundred cycles of oocyte donation at the University of Southern California: assessing the effect of age and infertility diagnosis on pregnancy and implantation rates. J. Assist. Reprod. Genet. 11, 92–96.
| Three hundred cycles of oocyte donation at the University of Southern California: assessing the effect of age and infertility diagnosis on pregnancy and implantation rates.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK2M7hvFGntw%3D%3D&md5=df9dfd518653b619db190eab0c3628c2CAS | 7819708PubMed |
Silva, E., Paczkowski, M., and Krisher, R. L. (2012). The effect of leptin on maturing porcine oocytes is dependent on glucose concentration. Mol. Reprod. Dev. 79, 296–307.
| The effect of leptin on maturing porcine oocytes is dependent on glucose concentration.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XivVSjsbw%3D&md5=48e64015a9342575003637d9af096264CAS | 22368147PubMed |
Simsek-Duran, F., Li, F., Ford, W., Swanson, R. J., Jones, H. W., and Castora, F. J. (2013). Age-associated metabolic and morphologic changes in mitochondria of individual mouse and hamster oocytes. PLoS ONE 8, e64955.
| Age-associated metabolic and morphologic changes in mitochondria of individual mouse and hamster oocytes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXpslOnsb8%3D&md5=0ad8e9aaf4e4b3f7ef9c14997d5b709fCAS | 23741435PubMed |
Suzuki, C., Yoshioka, K., Sakatani, M., and Takahashi, M. (2007). Glutamine and hypotaurine improves intracellular oxidative status and in vitro development of porcine preimplantation embryos. Zygote 15, 317–324.
| Glutamine and hypotaurine improves intracellular oxidative status and in vitro development of porcine preimplantation embryos.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXht1aqu7vI&md5=a01de8f2f7e2347a1e2bd2fcce3d2bbcCAS | 17967211PubMed |
Talebi, A., Zavareh, S., Kashani, M. H., Lashgarbluki, T., and Karimi, I. (2012). The effect of alpha lipoic acid on the developmental competence of mouse isolated preantral follicles. J. Assist. Reprod. Genet. 29, 175–183.
| The effect of alpha lipoic acid on the developmental competence of mouse isolated preantral follicles.Crossref | GoogleScholarGoogle Scholar | 22231012PubMed |
Tarín, J. J., Gómez-Piquer, V., Manzanedo, C., Miñarro, J., Hermenegildo, C., and Cano, A. (2003). Long-term effects of delayed motherhood in mice on postnatal development and behavioural traits of offspring. Hum. Reprod. 18, 1580–1587.
| Long-term effects of delayed motherhood in mice on postnatal development and behavioural traits of offspring.Crossref | GoogleScholarGoogle Scholar | 12871866PubMed |
Tilly, J. L., and Sinclair, D. A. (2013). Germline energetics, aging, and female infertility. Cell Metab. 17, 838–850.
| Germline energetics, aging, and female infertility.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXptV2msLw%3D&md5=809d9dca3043a4281ff7e4d1fb87b70dCAS | 23747243PubMed |
Tough, S., Tofflemire, K., Benzies, K., Fraser-Lee, N., and Newburn-Cook, C. (2007). Factors influencing childbearing decisions and knowledge of perinatal risks among Canadian men and women. Matern. Child Health J. 11, 189–198.
| Factors influencing childbearing decisions and knowledge of perinatal risks among Canadian men and women.Crossref | GoogleScholarGoogle Scholar | 17237994PubMed |
Uranga, R. M., Katz, S., and Salvador, G. A. (2013). Enhanced phosphatidylinositol 3-kinase (PI3K)/Akt signaling has pleiotropic targets in hippocampal neurons exposed to iron-induced oxidative stress. J. Biol. Chem. 288, 19 773–19 784.
| Enhanced phosphatidylinositol 3-kinase (PI3K)/Akt signaling has pleiotropic targets in hippocampal neurons exposed to iron-induced oxidative stress.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXhtVKntLbM&md5=98ba5859f3e5e49c12f9d7efa51680deCAS |
Van Blerkom, J., Davis, P. W., and Lee, J. (1995). ATP content of human oocytes and developmental potential and outcome after in-vitro fertilization and embryo transfer. Hum. Reprod. 10, 415–424.
| 1:STN:280:DyaK2M3os1OrtQ%3D%3D&md5=f1cafb1b1db144259abaa53545c16e55CAS | 7769073PubMed |
Wang, X., Falcone, T., Attaran, M., Goldberg, J. M., Agarwal, A., and Sharma, R. K. (2002). Vitamin C and vitamin E supplementation reduce oxidative stress-induced embryo toxicity and improve the blastocyst development rate. Fertil. Steril. 78, 1272–1277.
| Vitamin C and vitamin E supplementation reduce oxidative stress-induced embryo toxicity and improve the blastocyst development rate.Crossref | GoogleScholarGoogle Scholar | 12477524PubMed |
Wilding, M., Dale, B., Marino, M., di Matteo, L., Alviggi, C., Pisaturo, M. L., Lombardi, L., and De Placido, G. (2001). Mitochondrial aggregation patterns and activity in human oocytes and preimplantation embryos. Hum. Reprod. 16, 909–917.
| Mitochondrial aggregation patterns and activity in human oocytes and preimplantation embryos.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD3MvitlCktw%3D%3D&md5=1c4176cd537dfbb8c6bba9a06bd153d2CAS | 11331637PubMed |
Yuan, Y., Ida, J. M., Paczkowski, M., and Krisher, R. L. (2011). Identification of developmental competence-related genes in mature porcine oocytes. Mol. Reprod. Dev. 78, 565–575.
| Identification of developmental competence-related genes in mature porcine oocytes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhtValtbnE&md5=d5ccf06655a05c47c1179781a49824deCAS | 21774025PubMed |
Yuan, Y., Wheeler, M. B., and Krisher, R. L. (2012). Disrupted redox homeostasis and aberrant redox gene expression in porcine oocytes contribute to decreased developmental competence. Biol. Reprod. 87, 78.
| Disrupted redox homeostasis and aberrant redox gene expression in porcine oocytes contribute to decreased developmental competence.Crossref | GoogleScholarGoogle Scholar | 22811572PubMed |
Zhang, Y., and Yang, J. H. (2013). Activation of the PI3K/Akt pathway by oxidative stress mediates high glucose-induced increase of adipogenic differentiation in primary rat osteoblasts. J. Cell. Biochem. 114, 2595–2602.
| Activation of the PI3K/Akt pathway by oxidative stress mediates high glucose-induced increase of adipogenic differentiation in primary rat osteoblasts.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXhsVektbvK&md5=1500a90b49388402350b2e9692849d21CAS | 23757055PubMed |
Zhang, L., Hou, X., Ma, R., Moley, K., Schedl, T., and Wang, Q. (2014). Sirt2 functions in spindle organization and chromosome alignment in mouse oocyte meiosis. FASEB J. 28, 1435–1445.
| Sirt2 functions in spindle organization and chromosome alignment in mouse oocyte meiosis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXks1Sgtr4%3D&md5=b27def551166170525a636547d40276fCAS | 24334550PubMed |
