Skip to main content Accessibility help
Hostname: page-component-6c8bd87754-g6grg Total loading time: 1.03 Render date: 2022-01-17T08:38:28.036Z Has data issue: true Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "metricsAbstractViews": false, "figures": true, "newCiteModal": false, "newCitedByModal": true, "newEcommerce": true, "newUsageEvents": true }

Chapter 1 - Review of Cell and Molecular Biology

Published online by Cambridge University Press:  24 December 2019

Kay Elder
Bourn Hall Clinic, Cambridge
Brian Dale
Centre for Assisted Reproduction, Naples
Get access


Gametogenesis, embryo development, implantation and in-vitro culture involve numerous complex pathways and interactions at the cellular and molecular level; a true understanding of their significance requires fundamental knowledge of the underlying principles. This chapter therefore provides a condensed overview and review of basic terminology and definitions, with particular emphasis on aspects relevant to reproductive biology and in-vitro fertilization.

Publisher: Cambridge University Press
Print publication year: 2020

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)


Primary Sources

Barnum, KJ, O’Connell, MJ (2014). Cell cycle regulation by checkpoints. Methods in Molecular Biology 1170: 2940.CrossRefGoogle ScholarPubMed
Barrangou, R, Fremaux, C, Deveau, H, et al. (2007) CRISPR provides acquired resistance against viruses in prokaryotes. Science 315(5819): 17091712.CrossRefGoogle ScholarPubMed
Berg, JM, Tymoczko, JL, Stryer, L (eds.) (2002) Biochemistry, 5th edn. W H Freeman & Co., New York.Google Scholar
Biointeractive. CRISPR-Cas9 Mechanisms and Applications.
Dale, B (1983) Fertilization in Animals (Studies in Biology). Hodder, London.Google Scholar
Dale, B (2018) Fertilization: The Beginning of Life. Cambridge University Press, Cambridge.CrossRefGoogle Scholar
Hamilton, G (2015) The mitochondria mystery. Nature 525: 444446.CrossRefGoogle Scholar
Hassold, T, Hunt, P (2001) To err (meiotically) is human: the genesis of human aneuploidy. Nature Reviews Genetics 2: 280291.CrossRefGoogle Scholar
Hassold, T, Hall, H, Hunt, P (2007) The origin of human aneuploidy: where we have been, where we are going. Human Molecular Genetics 16(R2): R203R208.CrossRefGoogle ScholarPubMed
Hoffman, A, Sportelli, V, Ziller, M, Spengler, D (2017) Epigenomics of major depressive illness and schizophrenia: early life decides (Review). International Journal of Molecular Science 18(8): 1711.CrossRefGoogle Scholar
Hsu, PD, Lander, ES, Zhang, F (2014) Development and applications of CRISPR-Cas9 for genome engineering. Cell 157(6): 12621278.CrossRefGoogle ScholarPubMed
Johnson, MH (2017) Essential Reproduction, 7th edn. Blackwell Publishing, Oxford.Google Scholar
Lodish, H, Berk, A, Zipursky, SL, Matsudaira, P, Baltimore, D, Darnell, J (eds.) (2000) Molecular Cell Biology, 4th edn. W H Freeman & Co., New York.Google Scholar
Ménézo, Y (2017) Oxidative Stress and Women’s Health. Editions Eska, Paris, France.
Ménézo, Y, Dale, B, Cohen, M (2010) DNA damage and repair in human oocytes and embryos: a review. Zygote 18: 357365.CrossRefGoogle ScholarPubMed
Nagaoka, SI, Hassold, TJ, Hunt, PA (2012) Human aneuploidy: mechanisms and new insights into an age-old problem. Nature Reviews Genetics 13(7): 493504.CrossRefGoogle ScholarPubMed
National Academies of Sciences, Engineering and Medicine (2017) Human Genome Editing: Science, Ethics and Governance. The National Academies Press, Washington DC.
Nuffield Council on Bioethics (2018) Genome Editing and Human Reproduction: Social and Ethical Issues. Nuffield Council on Bioethics, London.
Richardson, B (2003) Impact of aging on DNA methylation. Ageing Research Reviews 2(3): 245261.CrossRefGoogle ScholarPubMed
Rozen, R (2004) Folate and genetics. Journal of Food Science and Technology 69(1): SNQ65SNQ67.Google Scholar
Skoot, R (2010) The Immortal Life of Henrietta Lacks. Crown Publishing Group, New York.Google Scholar
Tollefsbol, T (ed.) (2017) Handbook of Epigenetics: The New Molecular and Medical Genetics. 2nd edn. Academic Press, USA.Google Scholar
Van Blerkom, J (2004) Mitochondria in human oogenesis and preimplantation embryogenesis: engines of metabolism, ionic regulation and developmental competence. Reproduction 128: 269280.CrossRefGoogle ScholarPubMed
Webster, A & Schuh, M (2017) Mechanisms of aneuploidy in human eggs (Review). Trends in Cell Biology 27(1): 5568.CrossRefGoogle Scholar

Secondary Sources

Abudayyeh, OO, Gootenberg, JS, Konermann, S, et al (2016) C2c2 is a single-component programmable RNA-guided RNA-targeting CRISPR effector. Science 353: aaf5573.CrossRefGoogle ScholarPubMed
Akera, T, Lampson, MA (2016) Chromosome segregation: freewheeling sisters cause problems. eLife e13788. DOI: 10.7554/eLife.13788.CrossRef
Amar, E, Cornet, D, Cohen, M, Menezo, Y (2015) Treatment for high levels of sperm DNA fragmentation and nuclear decondensation: sequential treatment with a potent antioxidant followed by stimulation of the one-carbon cycle vs. one-carbon cycle back-up alone. Austin Journal of Reproductive Medicine and Infertility 2(1): 1006.Google Scholar
Barrangou, R, Horvath, P (2017) A decade of discovery: CRISPR functions and applications. Nature Microbiology 2: 17092. DOI: 10.1038/nmicrobiol.2017.92.CrossRefGoogle ScholarPubMed
Barrit, J, Kokot, T, Cohen, J, et al. (2002) Quantification of human ooplasmic mitochondria. Reproductive BioMedicine Online 4: 243237.CrossRefGoogle Scholar
Benkhalifa, M, Montjean, D, Cohen-Bacrie, P, Menezo, Y (2010) Imprinting: RNA expression for homocysteine recycling in the human oocyte. Fertility and Sterility 93: 1585-1590.CrossRefGoogle ScholarPubMed
Bennabi, I, Terret, M-E, Verlhac, M-H (2016) Meiotic spindle assembly and chromosome segregation in oocytes. Journal of Cell Biology 215(5): 611619.CrossRefGoogle ScholarPubMed
Berker, B, Kaya, C, Aytac, R, et al. (2009) Homocysteine concentrations in follicular fluid are associated with poor oocyte and embryo qualities in polycystic ovary syndrome patients undergoing assisted reproduction. Human Reproduction 24: 22932302.CrossRefGoogle ScholarPubMed
Cao, L, Wang, Y, Zhang, R, et al. (2018). Association of neural tube defects with gene polymorphisms in one-carbon metabolic pathway. Child’s Nervous System 34(2): 277284.CrossRefGoogle ScholarPubMed
Cappell, SD, Chung, M, Jaimovich, A, Spencer, SL, Meyer, T (2016) Irreversible APC (Cdh1) inactivation underlies the point of no return for cell-cycle entry. Cell 166: 167180.CrossRefGoogle ScholarPubMed
Chen, B, Gilbert, LA, Cimini, BA, et al. (2013) Dynamic imaging of genomic loci in living human cells by an optimized CRISPR/Cas systemCell 155(7): 14791491.CrossRefGoogle ScholarPubMed
Cheng, AW, Wang, H, Yang, H, et al. (2013) Multiplexed activation of endogenous genes by CRISPR-on, an RNA-guided transcriptional activator system. Cell Research 23: 11631171.CrossRefGoogle ScholarPubMed
Chen, JS, Ma, E, Harrington, LB, et al. (2018) CRISPR-Cas12a target binding unleashes indiscriminate single-stranded DNase activity. Science 360(6387): 436439.CrossRefGoogle ScholarPubMed
Cornet, D, Amar, E, Cohen, M, Menezo, Y (2015) Clinical evidence for the importance of 1-Carbon support in subfertile couples. Austin Journal of Reproductive Medicine and Infertility 2(2): 1011.Google Scholar
Cummins, JM (2002) The role of maternal mitochondria during oogenesis, fertilization and embryogenesis. Reproductive BioMedicine Online 4: 176182.CrossRefGoogle ScholarPubMed
Cyranoski, D, Ledford, H (2018) Genome-edited baby provokes international outcry. Nature 563 (7733): 607608.CrossRefGoogle ScholarPubMed
DeBaum, M, Niemitz, E, Feinberg, A (2003) Association of in vitro fertilization with Beckwith-Wiedemann syndrome and epigenetic alterations of LitI and H19. American Journal of Human Genetics 72: 156160.CrossRefGoogle Scholar
Ebisch, IM, Peters, WH, Thomas, CM, et al. (2006) Homocysteine, glutathione and related thiols affect fertility parameters in the (sub) fertile couple. Human Reproduction 21: 17251733.CrossRefGoogle ScholarPubMed
Ebisch, IM, Thomas, CM, Peters, WH (2007) The importance of folate, zinc and anti-oxidants in the pathogenesis and prevention of subfertility. Human Reproduction Update 13: 163174.CrossRefGoogle ScholarPubMed
Evenson, DP (2016) The sperm chromatin structure assay (SCSA) and other sperm DNA fragmentation tests for evaluation of sperm nuclear DNA integrity as related to fertility. Animal Reproduction Science 169: 56-75.CrossRefGoogle ScholarPubMed
Evenson, DP, Darzynkiewicz, Z, Melamed, MR (1980) Relation of mammalian sperm chromatin heterogeneity to fertility. Science 210: 11311133.CrossRefGoogle ScholarPubMed
Fonfara, I, Richter, H, Bratovic, M, Le Rhun, A, Charpentier, E (2016) The CRISPR-associated DNA-cleaving enzyme Cpf1 also processes precursor CRISPR RNA. Nature 532: 517521.CrossRefGoogle ScholarPubMed
Friedland, AE, Baral, B, Singhai, P, et al. (2015) Characterization of Staphylococcus aureus Cas9: a smaller Cas9 for all-in-one adeno-associated virus delivery and paired nickase applications. Genome Biology 16: 257.CrossRefGoogle ScholarPubMed
Friedmann, T, Jonlin, EC, King, NMP, et al. (2015) ASGCT and JSGT Joint Position Statement on Human Genomic Editing. Molecular Therapy 23(8): 1282.CrossRefGoogle ScholarPubMed
Fulka, J Jr., First, N, Moor, RM (1998) Nuclear and cytoplasmic determinants involved in the regulation of mammalian oocyte maturation. Molecular Human Reproduction 4(1): 4149.CrossRefGoogle ScholarPubMed
Guerin, P, El Mouatassim, S, Ménézo, Y (2001) Oxidative stress and protection against reactive oxygen species in the pre-implantation embryo and its surroundings. Human Reproduction Update 7: 175189.CrossRefGoogle ScholarPubMed
Hays, FA, Watson, J, Ho, Shing (2003) Caution! DNA crossing: crystal structures of Holliday junctions. Journal of Biological Chemistry 278(50): 4966349666.CrossRefGoogle ScholarPubMed
Hernando-Herrasez, I, Garcia-Perez, R, Sharp, AJ, Marques-Bonet, T (2015) DNA methylation: insights into human evolution. PLoS Genetics 11(12): 31005661.Google Scholar
Hilton, IB, D’Ippolito, AM, Vockley, CM, et al. (2015) Epigenome editing by a CRISPR-Cas9-based acetyltransferase activates genes from promoters and enhancers. Nature Biotechnology 33(5): 510517.CrossRefGoogle ScholarPubMed
Holubcova, Z, Blayney, M, Elder, K, Schuh, M (2015) Error-prone chromosome-mediated spindle assembly favors chromosome segregation defects in human oocytes. Science 348: 11431147.CrossRefGoogle ScholarPubMed
Hou, Z, Zhang, Y, Propson, NE, et al. (2013) Efficient genome engineering in human pluripotent stem cells using Cas9 from Neisseria meningitidis. Proceedings of the National Academy of Sciences USA 110: 1564415649.CrossRefGoogle ScholarPubMed
Hu, JH, Miller, SM, Geurts, MH, Tang, W, et al. (2018) EvolvedCas9 variants with broad PAM compatibility and high DNA specificity. Nature 556(7699): 5763.CrossRefGoogle ScholarPubMed
Huarte, J, Stutz, A, O’Connell, ML, et al. (1992) Transient translational silencing by reversible mRNA deadenylation. Cell 69: 10211030.CrossRefGoogle ScholarPubMed
Ishii, T (2017) Reproductive medicine involving genome editing: clinical uncertainties and embryological needs. Reproductive BioMedicine Online 34: 2731.CrossRefGoogle ScholarPubMed
Jinek, M, Chylinski, K, Fonfara, I, et al. (2012) A programmable dual RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337(6096): 816821.CrossRefGoogle ScholarPubMed
Kim, D, Bae, S, Park, J, et al. (2015) Digenome-seq: genome-wide profiling of CRISPR-Cas9 off-target effects in human cells. Nature Methods 12: 237243.CrossRefGoogle ScholarPubMed
Kim, E, Koo, T, Park, SW, et al. (2017) In vivo genome editing with a small Cas9 orthologue derived from Campylobacter jejuni. Nature Communications 8: 14500.CrossRefGoogle ScholarPubMed
Knouse, KA, Wu, J, Whittaker, CA, Amon, A (2014) Single cell sequencing reveals low levels of aneuploidy across mammalian tissues. Proceedings of the National Academy of Sciences USA 111: 1340913414.CrossRefGoogle ScholarPubMed
Komor, AC, Kim, YB, Packer, MS, Zuris, JA, Liu, DR (2016) Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage. Nature 533(7603): 420424.CrossRefGoogle ScholarPubMed
Kuliev, A, Zlatopolsky, Z, Kirillova, I, Spivakova, J, Cieslak Janzen, J (2011) Meiosis errors in over 20,000 oocytes studied in the practice of preimplantation aneuploidy testing. Reproductive BioMedicine Online 22: 28.CrossRefGoogle ScholarPubMed
Lander, ES (2015) Brave new genome. New England Journal of Medicine 373: 58.CrossRefGoogle ScholarPubMed
Liu, L, Chen, P, Wang, M, et al. (2017) C2c1–sgRNA complex structure reveals RNA-guided DNA cleavage mechanism. Molecular Cell 65: 310322.CrossRefGoogle Scholar
Luo, C, Valencia, CA, Zhang, J, et al. (2018) Biparental inheritance of mitochondrial DNA in humans. Proceedings of the National Academy of Sciences USA 115(51): 1303913044.CrossRefGoogle ScholarPubMed
Mali, P, Aach, J, Guell, M, et al. (2013) RNA-guided human genome engineering via Cas9. Science 339(6121): 823826.CrossRefGoogle ScholarPubMed
Marucci, GH, Zampieri, BL, Biselli, JM, et al. (2012) Polymorphism C1420T of serine hydroxymethyltransferase gene on maternal risk for Down syndrome. Molecular Biology Reports 39(3): 25612566.CrossRefGoogle ScholarPubMed
Ménézo, Y, Khatchadourian, C, Gharib, A, et al. (1989) Regulation of S-adenosyl methionine synthesis in the mouse embryo. Life Sciences 44: 16011609.CrossRefGoogle ScholarPubMed
Ménézo, YJR, Russo, G, Tosti, E, et al. (2007) Expression profile of genes coding for DNA repair in human oocytes using pangenomic microarrays, with a special focus on ROS linked decays. Journal of Assisted Reproduction and Genetics 24: 513520.CrossRefGoogle ScholarPubMed
Ménézo, Y, Mares, P, Cohen, M, et al. (2011) Autism, imprinting and epigenetic disorders: a metabolic syndrome linked to anomalies in homocysteine recycling starting in early life? Journal of Assisted Reproduction and Genetics 28: 11431145.CrossRefGoogle ScholarPubMed
Ménézo, Y, Entezami, F, Lichtblau, I, et al. (2014) Oxidative stress and fertility: incorrect assumptions and ineffective solutions? Zygote 22: 8090.CrossRefGoogle ScholarPubMed
Ménézo, Y, Silvestris, E, Dale, B, Elder, K (2016) Oxidative stress and alterations in DNA methylation: two sides of the same coin in reproduction. Reproductive BioMedicine Online 33(6): 668683.CrossRefGoogle ScholarPubMed
Ménézo, Y, Cornet, D, Cohen, M, et al. (2017) Association between the MTHFR-C677T isoform and structure of sperm DNA. Journal of Assisted Reproduction and Genetics 34(10): 12831288.Google Scholar
Moreno-Mateos, MA, Vejnar, CE, Beauddoin, JD, et al. (2015) CRISPRscan: designing highly efficient sgRNAs for CRISPR-Cas9 targeting in vivo. Nature Methods 12(10): 982988.CrossRefGoogle ScholarPubMed
Okamoto, Y, Yoshidda, N, Suzuki, T, et al. (2015) DNA methylation dynamics in mouse preimplantation embryos revealed by mass spectrometry. Scientific Reports 6: 19134. DOI: 10.1038/srep19134.CrossRefGoogle Scholar
Padmanabhan, N, Watson, ED (2013) Lessons from the one-carbon metabolism: passing it along to the next generation. Reproductive BioMedicine Online 27: 637643.CrossRefGoogle ScholarPubMed
Padmanabhan, N, Jia, D, Geary-Joo, C, et al. (2013) Mutation in folate metabolism causes epigenetic instability and transgenerational effects on development. Cell 155(1): 8193.CrossRefGoogle ScholarPubMed
Perez-Pinera, P, Kocak, DD, Vockley, CM, et al. (2013) RNA-guided gene activation by CRISPR-Cas9-based transcription factors. Nature Methods 10(10): 973976.CrossRefGoogle ScholarPubMed
Ran, FA, Cong, L, Yan, WX, et al. (2015) In vivo genome editing using Staphylococcus aureus Cas9. Nature 520: 186191.CrossRefGoogle ScholarPubMed
Sakakibara, Y, Hashimoto, S, Nakaoka, Y, Kouznetsova, A, Höög, C, Kitajima, TS (2015) Bivalent separation into univalents precedes age-related meiosis I errors in oocytes. Nature Communications 6: 7550.CrossRefGoogle ScholarPubMed
Sakkas, D, Urner, F, Bizzaro, D, et al. (1998) Sperm nuclear DNA damage and altered chromatin structure: effect on fertilization and embryo development. Human Reproduction 13(Suppl 4): 1119.CrossRefGoogle ScholarPubMed
Schuh, M, Ellenberg, J (2007) Self-organization of MTOCs replaces centrosome function during acentrosomal spindle assembly in live mouse oocytes. Cell 130: 484498.CrossRefGoogle ScholarPubMed
Sener, EF, Oztop, DB, Ozkui, Y (2014) MTHFR gene C677T polymorphism in autism spectrum disorders. Genetics Research International Art ID: 698574.
Sentmanat, MF, Peters, ST, Florian, CP, Connelly, JP, Pruett-Miller, SM (2018) A survey of validation strategies for CRISPR-Cas9 editing. Scientific Reports 8: Art No. 888.CrossRef
Shmakov, S, Abudayyeh, OO, Makarova, KS, et al. (2015) Discovery and functional characterization of diverse class 2 CRISPR-Cas systems. Molecular Cell 60: 385397.CrossRefGoogle ScholarPubMed
Sternberg, SH, Redding, S, Jinek, M, et al. (2014) DNA interrogation by the CRISPR RNA-guided endonuclease Cas9. Nature 506(7490): 6267.CrossRefGoogle Scholar
Sutovsky, P, Navara, CS, Schatten, G (1996) Fate of the sperm mitochondria, and the incorporation, conversion, and disassembly of the sperm tail structures during bovine fertilization. Biology of Reproduction 55: 11951205.CrossRefGoogle ScholarPubMed
Templado, C, Vidal, F, Estop, A (2011) Aneuploidy in human spermatozoa. Cytogenetic and Genome Research 133: 9199.CrossRefGoogle ScholarPubMed
Tsai, SQ, Nguyen, NT, Malagon-Lopez, J, Topkar, VV, Aryee, MJ, Joung, LK (2017) CIRCLE-seq: a highly sensitive in vitro screen for genome-wide CRISPR–Cas9 nuclease off-targets. Nature Methods 14: 607614.CrossRefGoogle ScholarPubMed
Tunster, SJ, Jensen, AB, John, RM (2013) Imprinted genes in mouse placental development and the regulation of fetal energy stores. Reproduction 145(5): R117R137.CrossRefGoogle ScholarPubMed
Vassena, R, Heindrycks, R, Peco, R, et al. (2016) Genome engineering through CRISPR/Cas9 technology in the human germline and pluripotent stem cells. Human Reproduction Update 22(4): 411419.CrossRefGoogle ScholarPubMed
Verlhac, MH, Terret, ME (2016) Oocyte maturation and development. F1000Research 5 (F1000 Faculty Rev): 309. DOI: 10.12688/f1000research.7892.1.CrossRefGoogle ScholarPubMed
Ward, WS (1993) Deoxyribonucleic acid loop domain tertiary structure in mammalian spermatozoa. Biology of Reproduction 48(6): 11931201.CrossRefGoogle ScholarPubMed
Watkins, D, Ru, M, Hwang, H-Y, et al. (2002) Hyperhomocysteinemia due to methionine synthase deficiency, cbIG: structure of the MTR gene, genotype diversity, and recognition of a common mutation, P1173L. American Journal of Human Genetics 71(1): 143153.CrossRefGoogle Scholar
Wernimont, SM, Raiszadeh, F, Stover, PJ, et al. (2011) Polymorphisms in serine hydroxymethyltransferase 1 and methylenetetrahydrofolate reductase interact to increase cardiovascular disease risk in humans. Journal of Nutrition 141(2): 255260.CrossRefGoogle ScholarPubMed
Wilding, MDale, BMarino, Met al. (2001) Mitochondrial aggregation patterns and activity in human oocytes and preimplantation embryos. Human Reproduction 16(5): 909917.CrossRefGoogle ScholarPubMed
Xu, W, Zhang, L, Wu, X, Jin, F (2017) Association between methionine synthase reductase A66G polymorphism and male infertility: a meta-analysis. Critical Reviews Eukaryotic Gene Expression 27(1): 3746.CrossRefGoogle ScholarPubMed
Yamano, T, Nishimasu, H, Zetsche, B, et al. (2016) Crystal structure of Cpf1 in complex with guide RNA and target DNA. Cell 165: 949962.CrossRefGoogle Scholar
Zemach, A, McDaniel, IE, Silva, P, Zilberman, D (2010) Genome-wide evolutionary analysis of eukaryotic DNA methylation. Science 328(5980): 916919.CrossRefGoogle ScholarPubMed
Zetsche, B, Gootenberg, JS, Abudayyeh, OO, et al. (2015) Cpf1 is a single RNA-guided endonuclease of a class 2 CRISPR-Cas system. Cell 163: 759771.CrossRefGoogle ScholarPubMed
Zielinska, AP, Holubcova, Z, Blayney, M, Elder, K, Schuh, M (2015) Sister kinetochore splitting and precocious disintegration of bivalents could explain the maternal age effect. eLife 4: e11389.CrossRefGoogle ScholarPubMed

Send book to Kindle

To send this book to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle.

Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats

Send book to Dropbox

To send content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about sending content to Dropbox.

Available formats

Send book to Google Drive

To send content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about sending content to Google Drive.

Available formats