Oocyte environment: follicular fluid and cumulus cells are critical for oocyte health
2014; Elsevier BV; Volume: 103; Issue: 2 Linguagem: Inglês
10.1016/j.fertnstert.2014.11.015
ISSN1556-5653
AutoresDaniel A. Dumesic, David R. Meldrum, Mandy G. Katz‐Jaffe, Rebecca L. Krisher, William B. Schoolcraft,
Tópico(s)Renal and related cancers
ResumoBidirectional somatic cell–oocyte signaling is essential to create a changing intrafollicular microenvironment that controls primordial follicle growth into a cohort of growing follicles, from which one antral follicle is selected to ovulate a healthy oocyte. Such intercellular communications allow the oocyte to determine its own fate by influencing the intrafollicular microenvironment, which in turn provides the necessary cellular functions for oocyte developmental competence, which is defined as the ability of the oocyte to complete meiosis and undergo fertilization, embryogenesis, and term development. These coordinated somatic cell–oocyte interactions attempt to balance cellular metabolism with energy requirements during folliculogenesis, including changing energy utilization during meiotic resumption. If these cellular mechanisms are perturbed by metabolic disease and/or maternal aging, molecular damage of the oocyte can alter macromolecules, induce mitochondrial mutations, and reduce adenosine triphosphate production, all of which can harm the oocyte. Recent technologies are now exploring transcriptional, translational, and post-translational events within the human follicle with the goal of identifying biomarkers that reliably predict oocyte quality in the clinical setting. Bidirectional somatic cell–oocyte signaling is essential to create a changing intrafollicular microenvironment that controls primordial follicle growth into a cohort of growing follicles, from which one antral follicle is selected to ovulate a healthy oocyte. Such intercellular communications allow the oocyte to determine its own fate by influencing the intrafollicular microenvironment, which in turn provides the necessary cellular functions for oocyte developmental competence, which is defined as the ability of the oocyte to complete meiosis and undergo fertilization, embryogenesis, and term development. These coordinated somatic cell–oocyte interactions attempt to balance cellular metabolism with energy requirements during folliculogenesis, including changing energy utilization during meiotic resumption. If these cellular mechanisms are perturbed by metabolic disease and/or maternal aging, molecular damage of the oocyte can alter macromolecules, induce mitochondrial mutations, and reduce adenosine triphosphate production, all of which can harm the oocyte. Recent technologies are now exploring transcriptional, translational, and post-translational events within the human follicle with the goal of identifying biomarkers that reliably predict oocyte quality in the clinical setting. Discuss: You can discuss this article with its authors and with other ASRM members at http://fertstertforum.com/dumesicd-oocyte-follicular-fluid-cumulus-cells/Human follicle development involves multiple intraovarian and endocrine interactions that create a changing intrafollicular microenvironment for optimal oocyte development. Bidirectional somatic cell–oocyte signaling via paracrine interactions regulates primordial follicle growth into a cohort of growing follicles, from which one antral follicle is selected to ovulate a developmentally competent oocyte, which is defined as the ability of the oocyte to complete meiosis and undergo fertilization, embryogenesis, and term development (1Schramm R.D. Bavister B.D. A macaque model for studying mechanisms controlling oocyte development and maturation in human and non-human primates.Hum Reprod. 1999; 14: 2544-2555Crossref PubMed Scopus (60) Google Scholar).According to the Society of Assisted Reproductive Technology, of 165,172 assisted reproductive cycles performed in 2012, only 40.6% of fresh nondonor IVF cycles in women less than 35 years of age lead to a live birth, with an embryo implantation rate of only 37.4% (2Society for Assisted Reproductive Technology SART CORS IVF Success Rates Clinic Summary Report.2012Google Scholar). Of these live births, 30.5% were multiple fetal pregnancies. Chromosomal screening of blastocysts and frozen ET techniques have increased IVF-related implantation rates to 65%–71% (3Scott Jr., R.T. Upham K.M. Forman E.J. Hong K.H. Scott K.L. 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Throughout folliculogenesis, oocyte-derived proteins of the transforming growth factor-β (TGFβ) superfamily (most notably, bone morphogenetic protein 15 [BMP15] and growth differentiation factor 9 [GDF9]) interact with surrounding somatic cells, which in turn produce their own paracrine factors (i.e., kit ligand, activins, inhibins, antimüllerian hormone [AMH], TGFα), to coordinate oocyte growth, granulosa cell proliferation, and theca cell differentiation (9Dumesic D. Abbott D. Accounting for the follicle population in the polycystic ovary.in: Dunaif A. Chang R.J. Franks S. Legro R. Polycystic ovary syndrome. Humana Press, Totowa, NJ2008: 9-24Crossref Google Scholar, 10Li R. Albertini D.F. The road to maturation: somatic cell interaction and self-organization of the mammalian oocyte.Nat Rev Mol Cell Biol. 2013; 14: 141-152Crossref PubMed Scopus (37) Google Scholar, 11Gosden R. Lee B. 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Activity of key enzymes involved in glucose and triglyceride catabolism during bovine oocyte maturation in vitro.Reproduction. 2002; 124: 675-681Crossref PubMed Google Scholar). Instead, cumulus cells with high glycolytic activity metabolize glucose into pyruvate, which transfers into the oocyte as an energy source during oocyte maturation (Fig. 1) (63Roberts R. Franks S. Hardy K. Culture environment modulates maturation and metabolism of human oocytes.Hum Reprod. 2002; 17: 2950-2956Crossref PubMed Google Scholar). Within the oocyte, pyruvate is converted in mitochondria to acetyl CoA, which enters the tricarboxylic acid (TCA) cycle and electron transport chain to produce adenosine triphosphate (ATP) (61Sutton-McDowall M.L. Gilchrist R.B. Thompson J.G. The pivotal role of glucose metabolism in determining oocyte developmental competence.Reproduction. 2010; 139: 685-695Crossref PubMed Scopus (76) Google Scholar). The oocyte in turn ensures its own delivery of pyruvate by up-regulating glycolytic genes in cumulus cells (7Seli E. Babayev E. Collins S.C. Nemeth G. Horvath T.L. Minireview: metabolism of female reproduction: regulatory mechanisms and clinical implications.Mol Endocrinol. 2014; 28: 790-804Crossref PubMed Scopus (1) Google Scholar, 64Sugiura K. Su Y.Q. Diaz F.J. Pangas S.A. Sharma S. Wigglesworth K. et al.Oocyte-derived BMP15 and FGFs cooperate to promote glycolysis in cumulus cells.Development. 2007; 134: 2593-2603Crossref PubMed Scopus (117) Google Scholar).Figure 2Linear regression lines for glucose versus lactate and P concentrations in follicles with mature oocytes from normoandrogenic ovulatory women (n = 25). A significant negative correlation exists between intrafollicular glucose and lactate levels (Y = −1.2X + 7.2, R2 = 0.55, P<.001), with a slope less than −2.0 (the molar ratio of lactate produced per glucose used by anaerobic glycolysis). A significant correlation also exists between intrafollicular glucose and P4 levels (Y = −14.9X + 81.6, R2 = 0.29, P<.007) (59Foong S.C. Abbott D.H. Zschunke M.A. Lesnick T.G. Phy J.L. Dumesic D.A. Follicle luteinization in hyperandrogenic follicles of polycystic ovary syndrome patients undergoing gonadotropin therapy for in vitro fertilization.J Clin Endocrinol Metab. 2006; 91: 2327-2333Crossref PubMed Scopus (30) Google Scholar).View Large Image Figure ViewerDownload Hi-res image Download (PPT)Within the COC, some glucose enters the pentose phosphate pathway (PPP) through glucose-6-phosphate dehydrogenase (G6PDH) to produce ribose-5-phosphate as a nucleotide precursor (65Gutnisky C. Dalvit G.C. Thompson J.G. Cetica P.D. Pentose phosphate pathway activity: effect on in vitro maturation and oxidative status of bovine oocytes.Reprod Fertil Dev. 2014; 26: 931-942Crossref PubMed Google Scholar). In this way, the PPP also controls the oxidative status of the oocyte by producing nicotinamide adenine dinucleotide phosphate (NADPH) as a cofactor for lipid, steroid, and nucleic acid synthesis (65Gutnisky C. Dalvit G.C. Thompson J.G. Cetica P.D. Pentose phosphate pathway activity: effect on in vitro maturation and oxidative status of bovine oocytes.Reprod Fertil Dev. 2014; 26: 931-942Crossref PubMed Google Scholar). Additional glucose enters the hexosamine biosynthesis pathway to provide substrate for hyaluronic acid production during extracellular matrix expansion and O-linked protein glycosylation for cell signaling and fuel sensing (61Sutton-McDowall M.L. Gilchrist R.B. Thompson J.G. The pivotal role of glucose metabolism in determining oocyte developmental competence.Reproduction. 2010; 139: 685-695Crossref PubMed Scopus (76) Google Scholar, 66Frank L.A. Sutton-McDowall M.L. Brown H.M. Russell D.L. Gilchrist R.B. Thompson J.G. 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