Hostname: page-component-848d4c4894-r5zm4 Total loading time: 0 Render date: 2024-06-21T07:52:37.421Z Has data issue: false hasContentIssue false
  • English
  • Français

Maternal folic acid depletion during early pregnancy increases sensitivity to squamous tumor formation in the offspring in mice

Published online by Cambridge University Press:  27 May 2019

Tomoyo Kawakubo-Yasukochi ,
Masahiko Morioka ,
Kenji Ohe ,
Atsushi Yasukochi ,
Yasuhiko Ozaki ,
Mai Hazekawa ,
Takuya Nishinakagawa ,
Kazuhiko Ono ,
Seiji Nakamura  and
Manabu Nakashima
Tomoyo Kawakubo-Yasukochi*
Affiliation:
Department of Immunological and Molecular Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan
Masahiko Morioka
Affiliation:
Department of Immunological and Molecular Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
Kenji Ohe
Affiliation:
Department of Pharmacotherapeutics, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan
Atsushi Yasukochi
Affiliation:
Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
Yasuhiko Ozaki
Affiliation:
Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan
Mai Hazekawa
Affiliation:
Department of Immunological and Molecular Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan
Takuya Nishinakagawa
Affiliation:
Department of Immunological and Molecular Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan
Kazuhiko Ono
Affiliation:
Department of Immunological and Molecular Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan
Seiji Nakamura
Affiliation:
Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
Manabu Nakashima
Affiliation:
Department of Immunological and Molecular Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan
*
Address for correspondence: Tomoyo Kawakubo-Yasukochi, Department of Immunological and Molecular Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan. Email: tomoyoyasu@fukuoka-u.ac.jp
Get access Rights & Permissions [Opens in a new window]

Abstract

Gestational nutrition is widely recognized to affect an offspring’s future risk of lifestyle-related diseases, suggesting the involvement of epigenetic mechanisms. As folic acid (FA) is a nutrient essential for modulating DNA methylation, we sought to determine how maternal FA intake during early pregnancy might influence tumor sensitivity in an offspring. Dams were maintained on a FA-depleted (FA(−)) or normal (2 mg FA/kg; FA(+)) diet from 2 to 3 days before mating to 7 days post-conception, and their offspring were challenged with chemical tumorigenesis using 7,12-dimethylbenz[a)anthracene and phorbol 12-myristate 13-acetate for skin and 4-nitroquinoline N-oxide for tongue. In both squamous tissues, tumorigenesis was more progressive in the offspring from FA(−) than FA(+) dams. Notably, in the skin of FA(−) offspring, the expression and activity of cylindromatosis (Cyld) were decreased due to the altered DNA methylation status in its promoter region, which contributed to increased tumorigenesis coupled with inflammation in the FA(−) offspring. Thus, we conclude that maternal FA insufficiency during early pregnancy is able to promote neoplasm progression in the offspring through modulating DNA methylation, such as Cyld. Moreover, we propose, for the first time, “innate” utero nutrition as the third cause of tumorigenesis besides the known causes—hereditary predisposition and acquired environmental factors.

Keywords

DOHaDfolatesquamous cell carcinomaCyld
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 10 , Issue 6 , December 2019 , pp. 683 - 691
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2019 

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

Barker, DJ, Osmond, C. Infant mortality, childhood nutrition, and ischaemic heart disease in England and Wales. Lancet. 1986; 1, 1077–1081.CrossRefGoogle ScholarPubMed
Gluckman, PD, Hanson, MA, Cooper, C, et al. Effect of in utero and early-life conditions on adult health and disease. N Engl J Med. 2008; 359, 61–73.CrossRefGoogle ScholarPubMed
Gluckman, PD, Hanson, MA. Living with the past: evolution, development, and patterns of disease. Science. 2004; 305, 1733–1736.CrossRefGoogle Scholar
Barker, DJ. A new model for the origins of chronic disease. Med Health Care Philos. 2001; 4, 31–35.CrossRefGoogle ScholarPubMed
Kawakubo-Yasukochi, T, Kondo, A, Mizokami, A, et al. Maternal oral administration of osteocalcin protects offspring from metabolic impairment in adulthood. Obesity. 2016; 24, 895–907.CrossRefGoogle ScholarPubMed
Waterland, RA. Early environmental effects on epigenetic regulation in humans. Epigenetics. 2009; 4, 523–525.CrossRefGoogle ScholarPubMed
Yang, M, Vousden, KH. Serine and one-carbon metabolism in cancer. Nat Rev Cancer. 2016; 16, 650–662.CrossRefGoogle Scholar
Lamprecht, SA, Lipkin, M. Chemoprevention of colon cancer by calcium, vitamin D and folate: Molecular mechanisms. Nat Rev Cancer. 2003; 3, 601–614.CrossRefGoogle ScholarPubMed
Fernandez, AF, Assenov, Y, Martin-Subero, JI, et al. A DNA methylation fingerprint of 1628 human samples. Genome Res. 2012; 22, 407–419.CrossRefGoogle ScholarPubMed
Feinberg, AP, Vogelstein, B. Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature. 1983; 301, 89–92.CrossRefGoogle ScholarPubMed
McKay, JA, Adriaens, M, Evelo, CT, et al. Gene promoter DNA methylation patterns have a limited role in orchestrating transcriptional changes in the fetal liver in response to maternal folate depletion during pregnancy. Mol Nutr Food Res. 2016; 60, 2031–2042.CrossRefGoogle ScholarPubMed
McKay, JA, Xie, L, Adriaens, M, et al. Organ-specific gene expression changes in the fetal liver and placenta in response to maternal folate depletion. Nutrients. 2016; 8, E661.CrossRefGoogle ScholarPubMed
Langie, SA, Achterfeldt, S, Gorniak, JP, et al. Maternal folate depletion and high-fat feeding from weaning affects DNA methylation and DNA repair in brain of adult offspring. FASEBJ. 2013; 27, 3323–3334.CrossRefGoogle ScholarPubMed
McKay, JA, Xie, L, Adriaens, M, et al. Maternal folate depletion during early development and high fat feeding from weaning elicit similar changes in gene expression, but not in DNA methylation, in adult offspring. Mol Nutr Food Re. 2017; s61, 1600713.CrossRefGoogle Scholar
Maldonado, E, López-Gordillo, Y, Partearroyo, T, et al. Tongue abnormalities are associated to a maternal folic acid deficient diet in mice. Nutrients. 2017; 10, E26.CrossRefGoogle ScholarPubMed
McKay, JA, Williams, EA, Mathers, JC. Effect of maternal and post-weaning folate supply on gene-specific DNA methylation in the small intestine of weaning and adult apc and wild type mice. Front Genet. 2011; 2, 23.CrossRefGoogle ScholarPubMed
Ji, YX, Huang, Z, Yang, X, et al. The deubiquitinating enzyme cylindromatosis mitigates nonalcoholic steatohepatitis. Nat Med. 2018; 24, 213–223.CrossRefGoogle ScholarPubMed
Massoumi, R, Kuphal, S, Hellerbrand, C, et al. Down-regulation of CYLD expression by Snail promotes tumor progression in malignant melanoma. J Exp Med. 2009; 206, 221–232.CrossRefGoogle ScholarPubMed
Annunziata, CM, Davis, RE, Demchenko, Y, et al. Frequent engagement of the classical and alternative NF-κB pathways by diverse genetic abnormalities in multiple myeloma. Cancer Cell. 2007; 12, 115–130.CrossRefGoogle ScholarPubMed
Bignell, GR, Warren, W, Seal, S, et al. Identification of the familial cylindromatosis tumour-suppressor gene. Nat Genet. 2000; 25, 160–165.CrossRefGoogle ScholarPubMed
Hellerbrand, C, Bumes, E, Bataille, F, et al. Reduced expression of CYLD in human colon and hepatocellular carcinomas. Carcinogenesis. 2007; 28, 21–27.CrossRefGoogle ScholarPubMed
Nikolaou, K, Tsagaratou, A, Eftychi, C, et al. Inactivation of the deubiquitinase CYLD in hepatocytes causes apoptosis, inflammation, fibrosis, and cancer. Cancer Cell. 2012; 21, 738–750.CrossRefGoogle Scholar
Hayashi, M, Jono, H, Shinriki, S, et al. Clinical significance of CYLD downregulation in breast cancer. Breast Cancer Res Treat. 2014; 143, 447–457.CrossRefGoogle ScholarPubMed
Alameda, JP, Fernández-Aceñero, MJ, Moreno-Maldonado, R, et al. CYLD regulates keratinocyte differentiation and skin cancer progression in humans. Cell Death Dis. 2011; 2, e208.CrossRefGoogle ScholarPubMed
Massoumi, R, Chmielarska, K, Hennecke, K, et al. Cyld inhibits tumor cell proliferation by blocking Bcl-3-dependent NF-κB signaling. Cell. 2006; 125, 665–677.CrossRefGoogle ScholarPubMed
Jin, YJ, Wang, S, Cho, J, et al. Epidermal CYLD inactivation sensitizes mice to the development of sebaceous and basaloid skin tumors. JCI Insight. 2016; 1, e86548.CrossRefGoogle ScholarPubMed
Reeves, PG. Components of the AIN-93 diets as improvements in the AIN-76A diet. J Nutr. 1997; 27, 838 S–841 S.CrossRefGoogle Scholar
Li, J, Liang, F, Yu, D, et al. Development of a 4-nitroquinoline-1-oxide model of lymph node metastasis in oral squamous cell carcinoma. Oral Oncol. 2013; 49, 299–305.CrossRefGoogle ScholarPubMed
Kawakubo, T, Yasukochi, A, Okamoto, K, et al. The role of cathepsin E in terminal differentiation of keratinocytes. Biol Chem. 2011; 392, 571–585.CrossRefGoogle ScholarPubMed
Thanos, D, Maniatis, T. NF-kappa B: A lesson in family values. Cell. 1995; 80, 529–532.CrossRefGoogle ScholarPubMed
Liang, G, Ahlqvist, K, Pannem, R, et al. Serum response factor controls CYLD expression via MAPK signaling pathway. PLoS One. 2011; 6, e19613.CrossRefGoogle ScholarPubMed
Crider, KS, Yang, TP, Berry, RJ, et al. Folate and DNA methylation: A review of molecular mechanisms and the evidence for folate’s role. Adv Nutr. 2012; 3, 21–38.CrossRefGoogle ScholarPubMed
Lim, JH, Jono, H, Koga, T, et al. Tumor suppressor CYLD acts as a negative regulator for non-typeable Haemophilus influenza-induced inflammation in the middle ear and lung of mice. PLoS One. 2007; 2, e1032.CrossRefGoogle Scholar
Arora, N, Bansal, MP, Koul, A. Azadirachta indica acts as a pro-oxidant and modulates cell cycle associated proteins during DMBA/TPA induced skin carcinogenesis in mice. Cell Biochem Funct. 2013; 31, 385–394.CrossRefGoogle ScholarPubMed
Pieroth, R, Paver, S, Day, S, et al. Folate and its impact on cancer risk. Curr Nutr Rep. 2018; 7, 70–84.CrossRefGoogle ScholarPubMed
Donnenfeld, M, Deschasaux, M, Latino-Martel, P, et al. Prospective association between dietary folate intake and skin cancer risk: Results from the Supplémentation en Vitamines et Minéraux Antioxydants cohort. Am J Clin Nutr. 2015; 102, 471–478.CrossRefGoogle ScholarPubMed
Galeone, C, Edefonti, V, Parpinel, M, et al. Folate intake and the risk of oral cavity and pharyngeal cancer: A pooled analysis within the international head and neck cancer epidemiology consortium. Int J Cancer. 2015; 136, 904–914.CrossRefGoogle ScholarPubMed
Kim, YI. Folate and colorectal cancer: an evidence-based critical review. Mol Nutr Food Res. 2007; 51, 267–292.CrossRefGoogle Scholar
Ulrich, CM, Potter, JD. Folate and cancer—timing is everything. JAMA. 2007; 297, 2408–2409.CrossRefGoogle Scholar
Wright, AJ, Dainty, JR, Finglas, PM. Folic acid metabolism in human subjects revisited: Potential implications for proposed mandatory folic acid fortification in the UK. Br J Nutr. 2007; 98, 667–675.CrossRefGoogle ScholarPubMed
Troen, AM, Mitchell, B, Sorensen, B, et al. Unmetabolized folic acid in plasma is associated with reduced natural killer cell cytotoxicity among postmenopausal women. J Nutr. 2006; 136, 189–194.CrossRefGoogle ScholarPubMed
Solanky, N, Requena Jimenez, A, D’Souza, SW, et al. Expression of folate transporters in human placenta and implications for homocysteine metabolism. Placenta. 2010; 31, 134–143.CrossRefGoogle ScholarPubMed
Plumptre, L, Masih, SP, Ly, A, et al. High concentrations of folate and unmetabolized folic acid in a cohort of pregnant Canadian women and umbilical cord blood. Am J Clin Nutr. 2015; 102, 848–857.CrossRefGoogle Scholar
Leamon, CP, Reddy, JA, Dorton, R, et al. Impact of high and low folate diets on tissue folate receptor levels and antitumor responses toward folate-drug conjugates. J Pharmacol Exp Ther. 2008; 327, 918–925.CrossRefGoogle ScholarPubMed
Salojin, KV, Cabrera, RM, Sun, W, et al. A mouse model of hereditary folate malabsorption: Deletion of the PCFT gene leads to systemic folate deficiency. Blood. 2011; 117, 4895–4904.CrossRefGoogle ScholarPubMed
Suzuki, R, Kohno, H, Suzui, M, et al. An animal model for the rapid induction of tongue neoplasm in human c-Ha-ras proto-oncogene transgenic rats by 4-nitroquinoline 1-oxide: Its potential use for preclinical chemoprevention studies. Carcinogenesis. 2006; 27, 619–630.CrossRefGoogle ScholarPubMed
Diepgen, TL, Mahler, V. The epidemiology of skin cancer. Br J Dermatol. 2002; 146, 1–6.CrossRefGoogle ScholarPubMed
Jemal, A, Thomas, A, Murray, T, et al. Cancer statistics, 2002. CA Cancer J Clin. 2002; 52, 23–47.CrossRefGoogle ScholarPubMed
Bailey, LB, Stover, PJ, McNulty, H, et al. Biomarkers of nutrition for development—folate review. J Nutr. 2015; 145, 1636 S–1680 S.CrossRefGoogle ScholarPubMed
Stark, KD, Pawlosky, RJ, Sokol, RJ, et al. Maternal smoking is associated with decreased 5-methyltetrahydrofolate in cord plasma. Am J Clin Nutr. 2007; 85, 796–802.CrossRefGoogle ScholarPubMed
Hutson, JR, Stade, B, Lehotay, DC, et al. Folic acid transport to the human fetus is decreased in pregnancies with chronic alcohol exposure. PLoS One. 2012; 7, e38057.CrossRefGoogle ScholarPubMed