Hostname: page-component-78c5997874-dh8gc Total loading time: 0 Render date: 2024-11-11T07:14:33.191Z Has data issue: false hasContentIssue false
  • English
  • Français

Folic acid supplementation during oocytes maturation influences in vitro production and gene expression of bovine embryos

Published online by Cambridge University Press:  09 March 2021

Carolina Gennari Verruma Open the ORCID record for Carolina Gennari Verruma [Opens in a new window] ,
Matheus Credendio Eiras ,
Artur Fernandes ,
Reginaldo Aparecido Vila ,
Cristiana Libardi Miranda Furtado ,
Ester Silveira Ramos  and
Raysildo Barbosa Lôbo
Carolina Gennari Verruma*
Affiliation:
Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil
Matheus Credendio Eiras
Affiliation:
Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil
Artur Fernandes
Affiliation:
Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil
Reginaldo Aparecido Vila
Affiliation:
Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil
Cristiana Libardi Miranda Furtado
Affiliation:
Drug Research and Development Center, Postgraduate Programme in Medical and Surgical Sciences, Federal University of Ceara, CE, Brazil
Ester Silveira Ramos
Affiliation:
Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil
Raysildo Barbosa Lôbo
Affiliation:
Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil
*
Author for correspondence: Carolina Gennari Verruma. Genetics Department, Medical School of Ribeirão Preto, Bandeirantes Avenue, 3900, 14049-900, São Paulo University, SP, Brazil. Tel: +55 16 3315 4909. E-mail: verruma.cg@usp.br
Get access Rights & Permissions [Opens in a new window]

Summary

Embryos that are produced in vitro frequently present epigenetic modifications. However, maternal supplementation with folic acid (FA) may improve oocyte maturation and embryo development, preventing epigenetic errors in the offspring. We sought to evaluate the influence of FA supplementation during in vitro maturation of grade I (GI) and grade III (GIII) bovine oocytes on embryo production rate and the expression of IGF2 and KCNQ1OT1 genes. The oocytes were matured in vitro with different concentrations of FA (0, 10, 30 and 100 μM), followed by in vitro fertilization and embryo culture. On the seventh day (D7) of culture, embryo production was evaluated and gene expression was measured using real-time qPCR. Supplementation with 10 μM of FA did not affect embryo production for GI and GIII oocytes. Moderate supplementation (30 μM) seemed to be a positive influence, increasing embryo production for GIII (P = 0.012), while the highest dose (100 μM) reduced embryo production (P = 0.010) for GI, and IGF2 expression was not detected. In GIII, only embryos whose oocyte maturation was not supplemented with FA demonstrated detected IGF2 expression. The lowest concentration of FA (10 μM) reduced KCNQ1OT1 expression (P = 0.05) on embryos from GIII oocytes. Different FA concentrations induced different effects on bovine embryo production and gene expression that was related to oocyte quality. Despite the epigenetic effects of FA, supplementation seems to be a promising factor to improve bovine embryo production if used carefully, as concentration is an important factor, especially in oocytes with impaired quality.

Keywords

Embryo early developmentEpigeneticsImprinted genesMethyl donorsOocyte supplementation
Type
Research Article
Information
Zygote , Volume 29 , Issue 5 , October 2021 , pp. 342 - 349
Copyright
© The Author(s), 2021. Published by Cambridge University Press

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.)

References

Assou, S, Boumela, I, Haouzi, D, Anahory, T, Dechaud, H, Vos, H and Hamamah, S (2010). Dynamic changes in gene expression during human early embryo development: from fundamental aspects to clinical applications. Hum Reprod Update 17, 272–90.CrossRefGoogle ScholarPubMed
Banerjee, A and Ray, S (2016). Structural exploration and conformational transitions in MDM2 upon DHFR interaction from Homo sapiens: a computational outlook for malignancy via epigenetic disruption. Scientifica 2016, 1–11.CrossRefGoogle ScholarPubMed
Bell, AC and Felsenfeld, G (2000). Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene. Nature 405, 482–5.CrossRefGoogle ScholarPubMed
Benkhalifa, M, Montjean, D, Cohen-Bacrie, P and Ménézo, Y (2010). Imprinting: RNA expression for homocysteine recycling in the human oocyte. Fertil Steril 93, 1585–90.CrossRefGoogle ScholarPubMed
Berry, RJ, Bailey, L, Mulinare, J, Bower, C and Dary, O (2010). Fortification of flour with folic acid. Food Nutr Bull 31(Suppl 1), S22–35.CrossRefGoogle ScholarPubMed
Boni, R, Cuomo, A and Tosti, E (2002). Developmental potential in bovine oocytes is related to cumulus–oocyte complex grade, calcium current activity, and calcium stores. Biol Reprod 66, 836–42.CrossRefGoogle ScholarPubMed
Bouckenheimer, J, Assou, S, Hou, C, Philippe, N, Sansac, C, Lavabre-Bertand, T, Commes, T, Lemaítre, J, Boureux, A and Vos, J (2016). Long non-coding RNAs in human early embryonic development and their potential in ART. Hum Reprod Update 23, 19–40.CrossRefGoogle ScholarPubMed
Boxmeer, JC, Macklon, NS, Lindemans, J, Beckers, NGM, Eijkemans, MJC, Laven, JSE, Steegers, EAP and Steegers-Theunissen, RPM (2009). IVF outcomes are associated with biomarkers of the homocysteine pathway in monofollicular fluid. Hum Reprod 24, 1059–66.CrossRefGoogle ScholarPubMed
Brioude, F, Lacoste, A, Netchine, I, Vazquez, MP, Auber, F, Audry, G, Gauthier-Villars, M, Brugieres, L, Gicquel, C, Le Bouc, Y and Rossignol, S (2013). Beckwith–Wiedemann syndrome: growth pattern and tumor risk according to molecular mechanism, and guidelines for tumor surveillance. Horm Res Paediatr 80, 457–65.CrossRefGoogle ScholarPubMed
Busso, D, Santander, N, Salas-Pérez, F and Santos, JL (2020). Nutrients and gene expression in development. In De Caterina, R, Martinez, JA and Kohlmeier, M (eds). Principles of Nutrigenetics and Nutrigenomics: Fundamentals of Individualized Nutrition, pp. 423–430. Elsevier Academic Press.CrossRefGoogle Scholar
Carli, D, Riberi, E, Ferrero, GB and Mussa, A (2020). Syndromic disorders caused by disturbed human imprinting. J Clin Res Pediatr Endocrinol 12, 1–16.CrossRefGoogle ScholarPubMed
Chen, Z, Robbins, KM, Wells, KD and Rivera, RM (2013). Large offspring syndrome: a bovine model for the human loss-of-imprinting overgrowth syndrome Beckwith–Wiedemann. Epigenetics 8, 591–601.CrossRefGoogle ScholarPubMed
Chen, Z, Hagen, DE, Elsik, CG, Ji, T, Morris, CJ, Moon, LE and Rivera, RM (2015). Characterization of global loss of imprinting in fetal overgrowth syndrome induced by assisted reproduction. PNAS 112, 4618–23.CrossRefGoogle ScholarPubMed
Cornet, D, Clement, A, Clement, P and Ménézo, Y (2019). High doses of folic acid induce a pseudo-methylenetetrahydrofolate syndrome. SAGE Open Med Case Rep 7, 1–4.Google ScholarPubMed
Crider, KS, Yang, TM, Berry, RJ and Bailey, LB (2012). Folate and DNA methylation: a review of molecular mechanisms and the evidence for folate’s role. Adv Nutr 3, 21–38.CrossRefGoogle ScholarPubMed
Czeizel, AE and Dudás, I (1992). Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation New Eng J Med 327, 1832–5.CrossRefGoogle ScholarPubMed
DeAngelis, AM, Martini, AE and Owen, CM (2018). Assisted reproductive technology and epigenetics. Semin Reprod Med 36, 221–32.CrossRefGoogle ScholarPubMed
DeBaun, MR, Niemitz, EL, McNeil, DE, Brandenburg, SA, Lee, MP and Feinberg, AP (2002). Epigenetic alterations of H19 and LIT1 distinguish patients with Beckwith–Wiedemann syndrome with cancer and birth defects. Am J Hum Genet 70, 604–11.CrossRefGoogle ScholarPubMed
DeBaun, MR, Niemitz, EL and Feinberg, AP (2003). Association of in vitro fertilization with Beckwith–Wiedemann syndrome and epigenetic alterations of LIT1 and H19. Am J Hum Genet 72, 156–60.CrossRefGoogle ScholarPubMed
Enciso, M, Sarasa, J, Xanthopoulou, L, Bristow, S, Bowles, M, Fragouli, E, Delhanty, J and Wells, D (2016). Polymorphisms in the MTHFR gene influence embryo viability and the incidence of aneuploidy. Hum Genet 135, 555–68.CrossRefGoogle ScholarPubMed
Friso, S, Santis, D and Pizzolo, F (2020). Vitamins and epigenetics. In Patel, V (ed.) Molecular Nutrition: Vitamins, pp. 633–50. Elsevier Inc.CrossRefGoogle Scholar
Froese, DS, Kopec, J, Rembeza, E, Bezerra, GA, Oberholzer, AE, Suormala, T, Lutz, S, Chalk, R, Borkowska, O, Baumgartner, MR and Yue, WW (2018). Structural basis for the regulation of human 5,10-methylenetetrahydrofolate reductase by phosphorylation and S-adenosylmethionine inhibition. Nat Commun 9, 1–13.CrossRefGoogle ScholarPubMed
Gaskins, AJ, Afeiche, M, Wright, DL, Toth, TL, Williams, PL, Gilman, MW, Hauser, R and Chavarro, JE (2015). Dietary folate and reproductive success among women undergoing assisted reproduction. Obstet Gynecol 124, 801–9.CrossRefGoogle Scholar
Gomes, MV, Huber, J, Ferriani, RA, Amaral Neto, AM and Ramos, ES (2009). Abnormal methylation at the KvDMR1 imprinting control region in clinically normal children conceived by assisted reproductive technologies. Mol Hum Reprod 15, 471–7.CrossRefGoogle Scholar
Gomes, S, Lopes, C and Pinto, E (2016). Folate and folic acid in the periconceptional period: Recommendations from official health organizations in thirty-six countries worldwide and WHO. Public Health Nutr 19, 176–89.CrossRefGoogle ScholarPubMed
Goodall, JJ and Schmutz, SM (2007). IGF2 gene characterization and association with rib eye area in beef cattle. Anim Genet 38, 154–61.CrossRefGoogle ScholarPubMed
Goossens, K, Soom, AV, Poucke, MV, Vandaele, L, Vandesompele, J, Zeveren, AV and Peelman, LJ (2007). Identification and expression analysis of genes associated with bovine blastocyst formation. BMC Dev Biol 7, 1–12.CrossRefGoogle ScholarPubMed
Hansen, PJ (2020). Implications of assisted reproductive technologies for pregnancy outcomes in mammals. Ann Rev Anim Biosci 8, 395–413.CrossRefGoogle ScholarPubMed
Harper, JC, Aittomaki, K, Borry, P, Cornel, MC, Werts, G, Dondorp, W, Geraedts, J, Gianaroli, L, Ketterson, K, Liebaers, I, Lundin, K, Mertes, H, Morris, M, Pennings, G, Sermon, K, Spits, C, Soini, S, van Montfoort, APA, Veiga, A, Vermeesch, JR, Viville, S, Macek, M Jr; on behalf of the European Society of Human Reproduction and Embryology and European Society of Human Genetics (2018). Recent developments in genetics and medically assisted reproduction: from research to clinical applications. Eur J Hum Genet 26, 12–33.CrossRefGoogle ScholarPubMed
Hattori, H, Hiura, H, Kitamura, A, Miyauchi, N, Kobayashi, N, Takahashi, S, Okae, H, Kyono, K, Kagami, M, Ogata, T and Arima, T (2019). Association of four imprinting disorders and ART. Clin Epigenet 1, 1–12.Google Scholar
Hoek, J, Koster, MPH Schoenmarkers, S, Willemsen, SP, Koning, AHJ Steegers, EAP and Steegers-Theunissen, RPM (2019). Does the father matter? The association between the periconceptional paternal folate status and embryonic growth. Fertil Steril 111, 270–9.CrossRefGoogle ScholarPubMed
Horike, S, Mitsuya, K, Meguro, M, Kotobuki, N, Kashiwagi, A, Notsu, T, Schulz, TC, Shirayoshi, Y and Oshimura, M (2000). Targeted disruption of the human LIT1 locus defines a putative imprinting control element playing an essential role in Beckwith–Wiedemann syndrome. Hum Mol Genet 9, 2075–83.CrossRefGoogle ScholarPubMed
Huang, X, Gao, S, Hou, S and Wu, Kun (2013). Folic acid facilitates in vitro maturation of mouse and Xenopus laevis oocytes. Brit J Nutr 109, 1389–95.CrossRefGoogle ScholarPubMed
Hussain, NM and Sharma, SC (2020). Flour fortification with folic acid to reduce risk of spina bifida. BSDJ 4, 45–9.CrossRefGoogle Scholar
Jiang, Z, Dong, H, Zheng, X, Marjani, SL, Donovan, DM, Chen, J and Tian, X (2015). mRNA levels of imprinted genes in bovine in vivo oocytes, embryos and cross species comparisons with humans, mice and pigs. Sci Rep 5, 1–10.CrossRefGoogle ScholarPubMed
Katari, S, Turan, N, Bibikova, M, Erinle, O, Chalian, R, Foster, G, Gaughan, J, Coutifaris, C, and Sapienza, C (2009). DNA methylation and gene expression differences in children conceived in vitro or in vivo. Hum Mol Genet 18, 3769–78.CrossRefGoogle ScholarPubMed
Kim, SE, Seo, JS, Eum, JH, Lim, JE, Kim, DH, Yoon, TK and Lee, DR (2009). The effect of folic acid on in vitro maturation and subsequent embryonic development of porcine immature oocytes. Mol Reprod Dev 76, 120–1.CrossRefGoogle ScholarPubMed
Kooistra, M, Trasler, JM and Baltz, JM (2013). Folate transport in mouse cumulus–oocyte complexes and preimplantation embryos. Biol Reprod 89, 1–9.CrossRefGoogle ScholarPubMed
Krishnaveni, GV, Veena, SR, Karat, SC, Yajnik, CS and Fall, CHD (2014). Association between maternal folate concentrations during pregnancy and insulin resistance in Indian children. Diabetologia 57, 110–21.CrossRefGoogle ScholarPubMed
Krupenko, NI (2019). Folate and vitamins B6 and B12. In De Caterina, R, Martinez, JA and Kohlmeier, M (eds). Principles of Nutrigenetics and Nutrigenomics: Fundamentals of Individualized Nutrition, pp. 295–302. Academic Press.Google Scholar
Kussano, NR, Leme, LO, Guimarães, ALS Franco, MM and Dode, MAN (2016). Molecular markers for oocyte competence in bovine cumulus cells. Theriogenology 85, 1167–76.CrossRefGoogle ScholarPubMed
Kwong, WY, Adamiak, SJ, Gwynn, A, Singh, R and Sinclair, KD (2010). Endogenous folates and single-carbon metabolism in the ovarian follicle, oocyte and pre-implantation embryo. Reproduction 139, 705–15.CrossRefGoogle ScholarPubMed
Leibfried, L and First, NL (1979). Characterization of bovine follicular oocytes and their ability to mature in vitro. J Anim Sci 48, 76–86.CrossRefGoogle ScholarPubMed
Lewis, A and Reik, W (2006). How imprinting centres work. Cytogenet Genome Res 113, 81–9.CrossRefGoogle ScholarPubMed
Lewis, A, Green, K, Dawson, C, Redrup, L, Huynh, KD, Lee, JT, Hemberger, M and Reik, W (2006). Epigenetic dynamics of the Kcnq1 imprinted domain in the early embryo. Development 133, 4203–10.CrossRefGoogle ScholarPubMed
Li, Y, Hagen, DE, Ji, T, Bakhtiarizadeh, MR, Frederic, WM, Traxler, EM, Kalish, JM and Rivera, RM (2019). Altered microRNA expression profiles in large offspring syndrome and Beckwith–Wiedemann syndrome. Epigenetics 14, 850–76.CrossRefGoogle ScholarPubMed
Liu, Y, Zhi, L, Shen, J, Li, S, Yao, J and Yang, X (2016). Effect of in ovo folic acid injection on hepatic IGF2 expression and embryo growth of broilers. J Anim Sci Biotechnol 7, 3–11.CrossRefGoogle ScholarPubMed
MacDonald, WA and Mann, MRW (2014). Epigenetic regulation of genomic imprinting from germ line to preimplantation. Mol Reprod Dev 81, 126–40.CrossRefGoogle ScholarPubMed
Mancini-DiNardo, D, Steele, SJS Levorse, JM, Ingram, RS and Tilghman, SM (2006). Elongation of the Kcnq1ot1 transcript is required for genomic imprinting of neighboring genes. Genes Dev 20, 1268–82.CrossRefGoogle ScholarPubMed
Mann, MRW and Watson, AJ (2013). Endogenous folate accumulation in oocytes and preimplantation embryos and its epigenetic implications. Biol Reprod 89, 1–2.CrossRefGoogle ScholarPubMed
Market-Velker, BA, Zhang, L, Magri, LS, Bonvissuto, AC and Mann, MRW (2010). Dual effects of superovulation: Loss of maternal and paternal imprinted methylation in a dose-dependent manner. Hum Mol Genet 19, 36–51.CrossRefGoogle ScholarPubMed
Institute of Medicine (US) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and its Panel on Folate, Other B Vitamins, and Choline (1998). Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington (DC): National Academies Press, 592 pp.Google Scholar
Meirelles, FV, Caetano, AR, Watanabe, YF, Ripamonte, P, Carambula, SF, Merighe, GK and Garcia, SM (2004). Genome activation and developmental block in bovine embryos. Anim Reprod Sci 82, 13–20.CrossRefGoogle ScholarPubMed
Mikael, LG, Deng, L, Paul, L, Selhub, J and Rozen, R (2013). Moderately high intake of folic acid has a negative impact on mouse embryonic development. Birth Defects Res A Clin Mol Teratol 97, 47–52.CrossRefGoogle Scholar
Miranda-Furtado, CL, Salomão, KB, Verruma, CG, Leite, SBP, Rios, AFL, Bialecka, M, Moustakas, I, Mei, H, Paz, CCP Duarte, G, Lopes, SMCS and Ramos, ES (2019). Variation in DNA methylation in the KvDMR1 (ICR2) region in first-trimester human pregnancies. Fertil Steril 1, 1–7.Google Scholar
Mitsuya, K, Meguro, M, Lee, MP, Katoh, M, Schulz, TC, Kugoh, H, Yoshida, MA, Niikawa, N, Feinberg, AP and Oshimura, M (1999). LIT1, an imprinted antisense RNA in the human KvLQT1 locus identified by screening for differentially expressed transcripts using monochromosomal hybrids. Hum Mol Genet 8, 1209–17.CrossRefGoogle ScholarPubMed
Mohammad, F, Mondal, T and Kanduri, C (2009). Epigenetics of imprinted long noncoding RNAs. Epigenetics 4, 277–86.CrossRefGoogle ScholarPubMed
Moore, T (2001). Genetic conflict, genomic imprinting and establishment of the epigenotype in relation to growth. Reproduction 122, 185–93.CrossRefGoogle Scholar
Murakami, K, Oshimura, M and Kugoh, H (2007). Suggestive evidence for chromosomal localization of non-coding RNA from imprinted LIT1. J Hum Genet 52, 926–33.CrossRefGoogle ScholarPubMed
Murrell, A, Heeson, S, Cooper, WN, Douglas, E, Apostolidou, S, Moore, GE, Maher, E and Reik, W (2004). An association between variants in the IGF2 gene and Beckwith–Wiedemann syndrome: interaction between genotype and epigenotype. Hum Mol Genet 13, 247–55.CrossRefGoogle ScholarPubMed
O’Neill, C (1998). Endogenous folic acid is essential for normal development of preimplantation embryos. Hum Reprod 13, 1312–6.CrossRefGoogle ScholarPubMed
O’Neill, MJ (2005). The influence of non-coding RNAs on allele-specific gene expression in mammals. Hum Mol Genet 14, 113–20.CrossRefGoogle ScholarPubMed
Pandey, RR, Mondal, T, Mohammad, F, Enroth, S, Redrup, L, Komorowski, J, Nagano, T, Mancini-DiNardo, D and Kanduri, C (2008). Kcnq1ot1 antisense noncoding RNA mediates lineage-specific transcriptional silencing through chromatin-level regulation. Mol Cell 32, 232–46.CrossRefGoogle ScholarPubMed
Patel, KR and Sobczyńska-Malefora, A (2017). The adverse effects of an excessive folic acid intake. Eur J Clin Nutr 71, 159–63.CrossRefGoogle ScholarPubMed
Pfaffl, MW (2001). A new mathematical for relative quantification in real-time RT-PCR. Nucl Acid Res 29, 16–21.CrossRefGoogle ScholarPubMed
Pickell, L, Brown, K, Li, D, Wang, Z-L Deng, L, Wu, Q, Selhub, J, Luo, L, Jerome-Majewska, L and Rozen, R (2011). High intake of folic acid disrupts embryonic development in mice. Birth Defects Res A Clin Mol Teratol 91, 8–19.CrossRefGoogle ScholarPubMed
Pizano, J and Willimson, CB (2020). Nutritional influences on methylation. In Noland, D, Drisko, JA, Wagner, L (eds). Integrative and Functional Medical Nutrition Therapy, pp. 269–84. Human Cham, Switzerland.CrossRefGoogle Scholar
Rahimi, S, Martel, J, Karahan, G, Angle, C, Behan, NA, Chan, D, MacFarlane, AJ and Trasler, JM (2019). Moderate maternal folic acid supplementation ameliorates adverse embryonic and epigenetic outcomes associated with assisted reproduction in a mouse model. Hum Reprod 34, 851–62.CrossRefGoogle ScholarPubMed
Reik, W, Dean, W and Walter, J (2001). Epigenetic reprogramming in mammalian development. Science 293, 1089–93.CrossRefGoogle ScholarPubMed
Rios, AFL Lemos, DC, Fernandes, MB, Andrea, MV, Gomes, MVM Lôbo, RB, Mazucato, M and Ramos, ES (2007). Expression of the CTCF gene in bovine oocytes and preimplantation embryos. Genet Mol Biol 30, 1202–5.CrossRefGoogle Scholar
Saini, N, Singh, MK, Shah, SM, Singh, KP, Kaushik, R, Manik, RS, Singla, SK, Palta, P and Chauhan, MS (2015). Developmental competence of different quality bovine oocytes retrieved through ovum pick-up following in vitro maturation and fertilization. Animal 9, 1979–85.CrossRefGoogle ScholarPubMed
Salilew-Wondim, D, Saeed-Zidane, M, Joelker, M, Gebremedhn, S, Poirier, M, Pandey, HO, Tholen, E, Neuhoff, C, Held, E, Besenfelder, U, Havlicek, V, Rings, F, Fournier, E, Gagné, D, Sirard, MA, Robert, C, Gad, A, Schellander, K and Tesfaye, D (2018). Genome-wide DNA methylation patterns of bovine blastocysts derived from in vivo embryos subjected to in vitro culture before, during or after embryonic genome activation. BMC Genomics 19, 1–19.CrossRefGoogle ScholarPubMed
Sato, D, Sakurai, K, Monji, Y, Kuwayama, T and Iwata, H (2013). Supplementation of maturation medium with folic acid affects DNA methylation of porcine oocytes and histone acetylation of early developmental stage embryos. J Mammal Ova Res 30, 109–16.CrossRefGoogle Scholar
Scaglione, F and Panzavolta, G (2014). Folate, folic acid and 5-methyltetrahydrofolate are not the same thing. Xenobiotica 44, 480–8.CrossRefGoogle Scholar
Schaefer, E and Nock, D (2019). The impact of preconceptional multiple-micronutrient supplementation on female fertility. Clin Med Insights Womens Health 12, 1–6.Google ScholarPubMed
Siqueira, LG, Silva, MVG Panetto, JC and Viana, JH (2020). Consequences of assisted reproductive technologies for offspring function in cattle. Reprod Fertil Dev 32, 82–97.CrossRefGoogle Scholar
Sirard, MA (2017). The influence of in vitro fertilization and embryo culture on the embryo epigenetic constituents and the possible consequences in the bovine model. J Dev Origins Health Dis 8, 1–7CrossRefGoogle ScholarPubMed
Smith, FM, Garfield, AS and Ward, A (2006). Regulation of growth and metabolism by imprinted genes. Cytogenet Genome Res 113, 279–91.CrossRefGoogle ScholarPubMed
Smith, LC, Therrien, J, Filion, F, Bressan, F and Meirelles, FV (2015). Epigenetic consequences of artificial reproductive technologies to the bovine imprinted genes SNRPN, H19/IGF2, and IGF2R. Front Genet 6, 1–6.CrossRefGoogle ScholarPubMed
Smithells, RW, Sheppard, S and Schorah, CJ (1976). Vitamin deficiencies and neural tube defects. Arch Dis Childhood 51, 944–50.CrossRefGoogle ScholarPubMed
Stampone, E, Caldarelli, I, Zullo, A, Bencivenga, D, Mancini, FP, Ragione, FD, Borriello, A (2018). Genetic and epigenetic control of CDKN1C expression: Importance in cell commitment and differentiation, tissue homeostasis and human diseases. Int J Mol Sci 19, 1–24.CrossRefGoogle ScholarPubMed
Steegers-Theunissen, RP, Obermann-Borst, SA, Kremer, D, Lindemans, J, Siebel, C, Steegers, EA, Slagboom, PE and Heijmans, BT (2009). Periconceptional maternal folic acid use of 400 μg per day is related to increased methylation of the IGF2 gene in the very young child. PLoS ONE, 4, 1–5.CrossRefGoogle Scholar
Suzuki, J, Therrien, J, Filion, F, Lefebvre, R, Goff, AK, Perecin, F, Meirelled, FV and Smith, LC (2011). Loss of methylation at H19 DMD is associated with biallelic expression and reduced development in cattle derived by somatic cell nuclear transfer. Biol Reprod 84, 947–56.CrossRefGoogle ScholarPubMed
Tamura, T and Picciano, MF (2006). Folate and human reproduction. Am J Clin Nutr J 83, 993–1016.CrossRefGoogle ScholarPubMed
Troen, AM, Mitchell, B, Sorensen, B, Wener, MH, Johnsin, A, Wood, B, Selhub, J, McTiernan Yasui, Y, Oral, E, Potter, JD and Ulrich, CM (2006). Unmetabolized folic acid in plasma is associated with reduced natural killer cell cytotoxicity among postmenopausal women. J Nutr 136, 189–94.CrossRefGoogle ScholarPubMed
Urrego, R, Rodriguez-Osorio, N and Niemann, H (2014). Epigenetic disorders and altered gene expression after use of assisted reproductive technologies in domestic cattle. Epigenetics 9, 803–15.CrossRefGoogle ScholarPubMed
Viana, J (2018). 2017 Statistics of embryo production and transfer in domestic farm animals: Is it a turning point? In 2017 more in vitro-produced than in vivo-derived embryos were transferred worldwide. Embryo Transfer Newsl 36, 1–13.Google Scholar
Wagner, C (2001). Biochemical role of folate in cellular metabolism. Clin Res Reg Affairs 18, 161–80.CrossRefGoogle Scholar
Walker, BN and Biase, FH (2020). The blueprint of RNA storages relative to oocyte developmental competence in cattle (Bos taurus). Biol Reprod 102, 784–94.CrossRefGoogle Scholar
Weksberg, R, Shuman, C and Beckwith, JB (2010). Beckwith–Wiedemann syndrome. Eur J Hum Genet 18, 8–14.CrossRefGoogle ScholarPubMed
Yamada, K, Strahler, JR, Andrews, PC and Matthews, RG (2005). Regulation of human methylenetetrahydrofolate reductase by phosphorylation. PNAS 102, 10454–9.CrossRefGoogle Scholar
Supplementary material: File

Gennari Verruma et al. supplementary material

Table S1

Download Gennari Verruma et al. supplementary material(File)
File 14.3 KB