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Journal of Assisted Reproduction and Genetics

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15.09.2020 | Assisted Reproduction Technologies

Mitochondrial metabolic substrate utilization in granulosa cells reflects body mass index and total follicle stimulating hormone dosage in in vitro fertilization patients

verfasst von: Richard J. Kordus, Akhtar Hossain, Henry E. Malter, Holly A. LaVoie

Erschienen in: Journal of Assisted Reproduction and Genetics | Ausgabe 11/2020

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Abstract

Purpose

To utilize a novel mitochondrial function assay with pooled granulosa cells to determine whether mitochondrial function would differ by patient demographics and embryo development.

Methods

This was a prospective pilot study in a hospital-based assisted reproductive program and public university. Mitochondrial metabolic substrate utilization was assessed in pooled granulosa cells from 40 women undergoing in vitro fertilization during 2018 and 2019.

Results

Assessment of mitochondrial substrate metabolism in pooled granulosa cells revealed higher citric acid, L-malic acid, and octanoyl-L-carnitine utilization with higher body mass index (BMI). Utilization of citric acid, cis-aconitic acid, D-alpha-keto-glutaric acid, L-glutamine, and alanine plus glycine was significantly lower as total dosage of FSH administered increased. Utilization of glycogen was significantly higher in patients with a higher percentage of fertilized oocytes. D-alpha-keto-glutaric acid utilization was significantly lower in patients with a higher percentage of good 8-cell embryos. L-glutamine utilization was significantly lower, with a higher percentage of blastocyst formation. Mitochondrial metabolic scores (MMS), which reflect overall mitochondrial activity of the granulosa pool, were significantly higher in patients with higher BMI and with greater numbers of mature oocytes retrieved. MMS in granulosa decreased as total FSH dose administered increased.

Conclusions

Granulosa cell utilization of substrates feeding into the citric acid cycle changed with total FSH dosage and BMI. Fertilization rate, 8-cell embryo quality, and blastocyst formation also associated with different energy substrate usage. Mitochondrial substrate utilization by granulosa cells from individual follicles could be further developed into a useful diagnostic tool.

Nur mit Berechtigung zugänglich

Margulis L. Archaeal-eubacterial mergers in the origin of Eukarya: phylogenetic classification of life. Proc Natl Acad Sci U S A. 1996;93(3):1071–6. https://doi.org/10.1073/pnas.93.3.1071.CrossRef

Seyfried TN, Shelton LM. Cancer as a metabolic disease. Nutr Metab (Lond). 2010;7:7. doi:https://doi.org/10.1186/1743-7075-7-7.

Veatch JR, McMurray MA, Nelson ZW, Gottschling DE. Mitochondrial dysfunction leads to nuclear genome instability via an iron-sulfur cluster defect. Cell. 2009;137(7):1247–58. https://doi.org/10.1016/j.cell.2009.04.014.CrossRef

Boucret L, JM CdlB, Moriniere C, Desquiret V, Ferre-L'Hotellier V, Descamps P et al. Relationship between diminished ovarian reserve and mitochondrial biogenesis in cumulus cells. Hum Reprod. 2015;30(7):1653–64. doi:dev114 [pii];https://doi.org/10.1093/humrep/dev114.

Pawlak P, Chabowska A, Malyszka N, Lechniak D. Mitochondria and mitochondrial DNA in porcine oocytes and cumulus cells--a search for developmental competence marker. Mitochondrion. 2016;27:48–55. https://doi.org/10.1016/j.mito.2015.12.008.CrossRef

Collado-Fernandez E, Picton HM, Dumollard R. Metabolism throughout follicle and oocyte development in mammals. Int J Dev Biol. 2012;56(10–12):799–808. https://doi.org/10.1387/ijdb.120140ec.CrossRef

Su YQ, Sugiura K, Eppig JJ. Mouse oocyte control of granulosa cell development and function: paracrine regulation of cumulus cell metabolism. Semin Reprod Med. 2009;27(1):32–42. https://doi.org/10.1055/s-0028-1108008.CrossRef

Sutton-McDowall ML, Gilchrist RB, Thompson JG. The pivotal role of glucose metabolism in determining oocyte developmental competence. Reproduction. 2010;139(4):685–95. https://doi.org/10.1530/REP-09-0345.CrossRef

Dalton CM, Szabadkai G, Carroll J. Measurement of ATP in single oocytes: impact of maturation and cumulus cells on levels and consumption. J Cell Physiol. 2014;229(3):353–61. https://doi.org/10.1002/jcp.24457.CrossRef

10.

Huang Z, Wells D. The human oocyte and cumulus cells relationship: new insights from the cumulus cell transcriptome. Mol Hum Reprod. 2010;16(10):715–25. doi:gaq031 [pii];https://doi.org/10.1093/molehr/gaq031.

11.

Tsai HD, Hsieh YY, Hsieh JN, Chang CC, Yang CY, Yang JG, et al. Mitochondria DNA deletion and copy numbers of cumulus cells associated with in vitro fertilization outcomes. J Reprod Med. 2010;55(11–12):491–7.

12.

Desquiret-Dumas V, Clement A, Seegers V, Boucret L, Ferre-L'Hotellier V, Bouet PE, et al. The mitochondrial DNA content of cumulus granulosa cells is linked to embryo quality. Hum Reprod. 2017;32(3):607–14. https://doi.org/10.1093/humrep/dew341.CrossRef

13.

Diez-Juan A, Rubio C, Marin C, Martinez S, Al-Asmar N, Riboldi M, et al. Mitochondrial DNA content as a viability score in human euploid embryos: less is better. Fertil Steril. 2015;104(3):534–41 e1. https://doi.org/10.1016/j.fertnstert.2015.05.022.CrossRef

14.

Fragouli E, Wells D. Mitochondrial DNA assessment to determine oocyte and embryo viability. Semin Reprod Med. 2015;33(6):401–9. https://doi.org/10.1055/s-0035-1567821.CrossRef

15.

Ogino M, Tsubamoto H, Sakata K, Oohama N, Hayakawa H, Kojima T, et al. Mitochondrial DNA copy number in cumulus cells is a strong predictor of obtaining good-quality embryos after IVF. J Assist Reprod Genet. 2016;33(3):367–71. https://doi.org/10.1007/s10815-015-0621-0.CrossRef

16.

Bochner BR, Gadzinski P, Panomitros E. Phenotype microarrays for high-throughput phenotypic testing and assay of gene function. Genome Res. 2001;11(7):1246–55. https://doi.org/10.1101/gr.186501.CrossRef

17.

Racowsky C, Vernon M, Mayer J, Ball GD, Behr B, Pomeroy KO, et al. Standardization of grading embryo morphology. J Assist Reprod Genet. 2010;27(8):437–9. https://doi.org/10.1007/s10815-010-9443-2.CrossRef

18.

Vanderstichel R, Dohoo I, Markham F. Applying a kinetic method to an indirect ELISA measuring Ostertagia ostertagi antibodies in milk. Can J Vet Res. 2015;79(3):180–3.

19.

Bates D, Machler M, Bolker B, Walker S. Fitting linear mixed-effects models using lme4. J Stat Softw. 2015;67(1):1–48. doi: https://doi.org/10.18637/jss.v067/i01.

20.

Sermondade N, Huberlant S, Bourhis-Lefebvre V, Arbo E, Gallot V, Colombani M, et al. Female obesity is negatively associated with live birth rate following IVF: a systematic review and meta-analysis. Hum Reprod Update. 2019;25(4):439–51. https://doi.org/10.1093/humupd/dmz011.CrossRef

21.

Hauck AK, Bernlohr DA. Oxidative stress and lipotoxicity. J Lipid Res. 2016;57(11):1976–86. https://doi.org/10.1194/jlr.R066597.CrossRef

22.

Gorshinova VK, Tsvirkun DV, Sukhanova IA, Tarasova NV, Volodina MA, Marey MV, et al. Cumulus cell mitochondrial activity in relation to body mass index in women undergoing assisted reproductive therapy. BBA Clin. 2017;7:141–6. https://doi.org/10.1016/j.bbacli.2017.03.005.CrossRef

23.

Abraham M, Collins CA, Flewelling S, Camazine M, Cahill A, Cade WT, et al. Mitochondrial inefficiency in infants born to overweight African-American mothers. Int J Obes. 2018;42(7):1306–16. https://doi.org/10.1038/s41366-018-0051-z.CrossRef

24.

Broekmans FJ. Individualization of FSH doses in assisted reproduction: facts and fiction. Front Endocrinol (Lausanne). 2019;10:181. doi:https://doi.org/10.3389/fendo.2019.00181.

25.

Fedorcsak P, Dale PO, Storeng R, Ertzeid G, Bjercke S, Oldereid N, et al. Impact of overweight and underweight on assisted reproduction treatment. Hum Reprod. 2004;19(11):2523–8. https://doi.org/10.1093/humrep/deh485.CrossRef

26.

Borges E Jr, Zanetti BF, Setti AS, Braga DP, Figueira RCS, Iaconelli A Jr. FSH dose to stimulate different patient' ages: when less is more. JBRA Assist Reprod. 2017;21(4):336–42. https://doi.org/10.5935/1518-0557.20170058.CrossRef

27.

Saito N, Yamashita Y, Ono Y, Higuchi Y, Hayashi A, Yoshida Y, et al. Difference in mitochondrial gene expression in granulosa cells between recombinant FSH and hMG cycles under in vitro fertilization and transfer. Reprod Med Biol. 2013;12(3):99–104. https://doi.org/10.1007/s12522-013-0147-z.CrossRef

28.

Bentov Y, Yavorska T, Esfandiari N, Jurisicova A, Casper RF. The contribution of mitochondrial function to reproductive aging. J Assist Reprod Genet. 2011;28(9):773–83. https://doi.org/10.1007/s10815-011-9588-7.CrossRef

29.

May-Panloup P, Chretien MF, Jacques C, Vasseur C, Malthiery Y, Reynier P. Low oocyte mitochondrial DNA content in ovarian insufficiency. Hum Reprod. 2005;20(3):593–7. https://doi.org/10.1093/humrep/deh667.CrossRef

30.

Reynier P, May-Panloup P, Chretien MF, Morgan CJ, Jean M, Savagner F, et al. Mitochondrial DNA content affects the fertilizability of human oocytes. Mol Hum Reprod. 2001;7(5):425–9. https://doi.org/10.1093/molehr/7.5.425.CrossRef

31.

Zhao SY, Qiao J, Chen YJ, Liu P, Li J, Yan J. Expression of growth differentiation factor-9 and bone morphogenetic protein-15 in oocytes and cumulus granulosa cells of patients with polycystic ovary syndrome. Fertil Steril. 2010;94(1):261–7. doi:S0015–0282(09)00533–0 [pii];https://doi.org/10.1016/j.fertnstert.2009.03.014 .

32.

Dumesic DA, Guedikian AA, Madrigal VK, Phan JD, Hill DL, Alvarez JP, et al. Cumulus cell mitochondrial resistance to stress in vitro predicts oocyte development during assisted reproduction. J Clin Endocrinol Metab. 2016;101(5):2235–45. https://doi.org/10.1210/jc.2016-1464.CrossRef

33.

Brogan RS, MacGibeny M, Mix S, Thompson C, Puttabyatappa M, VandeVoort CA, et al. Dynamics of intra-follicular glucose during luteinization of macaque ovarian follicles. Mol Cell Endocrinol. 2011;332(1–2):189–95. https://doi.org/10.1016/j.mce.2010.10.011.CrossRef

34.

Taugourdeau A, Desquiret-Dumas V, Hamel JF, Chupin S, Boucret L, Ferre-L'Hotellier V, et al. The mitochondrial DNA content of cumulus cells may help predict embryo implantation. J Assist Reprod Genet. 2019;36(2):223–8. https://doi.org/10.1007/s10815-018-1348-5.CrossRef

35.

Murakoshi Y, Sueoka K, Takahashi K, Sato S, Sakurai T, Tajima H, et al. Embryo developmental capability and pregnancy outcome are related to the mitochondrial DNA copy number and ooplasmic volume. J Assist Reprod Genet. 2013;30(10):1367–75. https://doi.org/10.1007/s10815-013-0062-6.CrossRef

36.

Santos TA, El Shourbagy S, St John JC. Mitochondrial content reflects oocyte variability and fertilization outcome. Fertil Steril. 2006;85(3):584–91. https://doi.org/10.1016/j.fertnstert.2005.09.017.CrossRef

37.

Kordus RJ, LaVoie HA. Granulosa cell biomarkers to predict pregnancy in ART: pieces to solve the puzzle. Reproduction. 2017;153(2):R69-R83. doi:REP-16-0500 [pii];https://doi.org/10.1530/REP-16-0500.

38.

Bochner BR, Siri M, Huang RH, Noble S, Lei XH, Clemons PA, et al. Assay of the multiple energy-producing pathways of mammalian cells. PLoS One. 2011;6(3):e18147. https://doi.org/10.1371/journal.pone.0018147.CrossRef

39.

Kuzniewska B, Cysewski D, Wasilewski M, Sakowska P, Milek J, Kulinski TM et al. Mitochondrial protein biogenesis in the synapse is supported by local translation. EMBO Rep. 2020:e48882. doi:https://doi.org/10.15252/embr.201948882.

Titel: Mitochondrial metabolic substrate utilization in granulosa cells reflects body mass index and total follicle stimulating hormone dosage in in vitro fertilization patients
verfasst von: Richard J. Kordus
Akhtar Hossain
Henry E. Malter
Holly A. LaVoie
Publikationsdatum: 15.09.2020
Verlag: Springer US
Erschienen in: Journal of Assisted Reproduction and Genetics / Ausgabe 11/2020
Print ISSN: 1058-0468
Elektronische ISSN: 1573-7330
DOI: https://doi.org/10.1007/s10815-020-01946-9

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Mitochondrial metabolic substrate utilization in granulosa cells reflects body mass index and total follicle stimulating hormone dosage in in vitro fertilization patients

Abstract

Purpose

Methods

Results

Conclusions

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Abstract

Purpose

Methods

Results

Conclusions

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