Hostname: page-component-cd9895bd7-gvvz8 Total loading time: 0 Render date: 2024-12-28T20:01:21.821Z Has data issue: false hasContentIssue false
  • English
  • Français

Dietary genistein stimulates mammary hyperplasia in gilts

Published online by Cambridge University Press:  30 October 2009

C. Farmer ,
M. F. Palin ,
G. S. Gilani ,
H. Weiler ,
M. Vignola ,
R. K. Choudhary  and
A. V. Capuco
C. Farmer*
Affiliation:
Agriculture and Agri-Food Canada, Dairy and Swine Research and Development Centre, P.O. Box 90, Lennoxville STN, Sherbrooke QC J1M 1Z3, Canada
M. F. Palin
Affiliation:
Agriculture and Agri-Food Canada, Dairy and Swine Research and Development Centre, P.O. Box 90, Lennoxville STN, Sherbrooke QC J1M 1Z3, Canada
G. S. Gilani
Affiliation:
Nutrition Research Division, Health Canada, Ottawa, ON K1A 0L2, Canada
H. Weiler
Affiliation:
School of Dietetics and Human Nutrition, McGill University, Ste-Anne-de-Bellevue, QC H9X 3V9, Canada
M. Vignola
Affiliation:
NUTRECO, Brossard, QC J4W 3E7, Canada
R. K. Choudhary
Affiliation:
Department of Animal and Avian Science, University of Maryland, College Park, MD 20742, USA
A. V. Capuco
Affiliation:
USDA-ARS, Bovine Functional Genomics Lab, Beltsville, MD 20705, USA
*
†E-mail: Chantal.Farmer@agr.gc.ca
Get access

Abstract

The possible role of the phytoestrogen genistein on prepubertal development of mammary glands, hormonal status and bone resorption was investigated in gilts. Forty-five gilts were fed a control diet containing soya (CTLS, n = 15), a control diet without soya (CTL0, n = 15) or the CTLS diet supplemented with 2.3 g of genistein daily (GEN, n = 15) from 90 days of age until slaughter (day 183 ± 1). Both basal diets were isonitrogenous and isocaloric. Jugular blood samples were obtained on days 89 and 176 to determine concentrations of isoflavone metabolites (on day 176 only), prolactin, estradiol, progesterone, insulin-like growth factor 1 (IGF1), and N-telopeptide of type I collagen (NTx; on day 176 only). At slaughter, mammary glands were excised, parenchymal and extraparenchymal tissues were dissected, and composition of parenchymal tissue (protein, fat, dry matter (DM), DNA) was determined. Histochemical analyses of mammary parenchyma were performed. Dietary genistein increased parenchymal protein (P < 0.05) while decreasing DM (P < 0.05) and tending to lower fat content compared with the CTLS, but not the CTL0, diet. There was more parenchymal DNA (1.26 v. 0.92 mg/g, P < 0.05) in GEN than CTLS gilts, likely reflecting an increase in the quantity of mammary epithelial cells. Circulating concentrations of genistein were increased in GEN gilts (P < 0.001) but concentrations of hormones or NTx (indicator of bone collagen resorption) were not affected by GEN (P > 0.1). Percentage of estradiol receptor alpha (ERα)-positive epithelial cells was lower (P < 0.05) in GEN than CTLS gilts, whereas 5-bromo-2′-deoxyuridine labeling index was unaltered (P > 0.1). Transcript levels for ERα, ERβ, IGF1, epidermal growth factor (EGF), epidermal growth factor receptor and transforming growth factor alpha were not altered by treatments. Supplementation of the diet with genistein during the growing phase in gilts, therefore, led to hyperplasia of mammary parenchymal tissue after puberty; yet, even though circulating genistein was increased, this was not accompanied by changes in mammary expression of selected genes or circulating hormone levels.

Keywords

genistein, mammary glands, phytoestrogen, pigs, puberty
Type
Full Paper
Information
animal , Volume 4 , Issue 3 , March 2010 , pp. 454 - 465
Copyright
Copyright © The Animal Consortium 2009

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

Abribat, T, Brazeau, P, Davignon, I, Garrel, DR 1993. Insulin-like growth factor-I blood levels in severely burned patients: Effect of time post-injury, age of patient and severity of burn. Clinical Endocrinology 39, 583–589.CrossRefGoogle ScholarPubMed
Adlercreutz, H, Höckerstedt, K, Bannwart, C, Bloigu, S, Hämäläinen, E, Fotsis, T, Ollus, A 1987. Effect of dietary components, including lignans and phytoestrogens, on enterohepatic circulation and liver metabolism of estrogens and on sex hormone binding globulin (SHBG). Journal of Steroid Biochemistry 27, 1135–1144.CrossRefGoogle ScholarPubMed
Agriculture and Agri-Food Canada 1993. Recommended code of practice for the care and handling of farm animals – pigs, publication number 1898E. Agriculture and Agri-Food Canada, Ottawa, ON.Google Scholar
Applied Biosystems 1997. User Bulletin No. 2: ABI PRISM 7700 Sequence Detection System. Applied Biosystems, Foster City, CA, USA.Google Scholar
Association of Official Analytical Chemists (AOAC) 2004. Official methods of analysis, volume 2, 18th edition. AOAC, Arlington, VA, USA.Google Scholar
Atkinson, C, Compston, JE, Day, NE, Dowsett, M, Bingham, SA 2004. The effects of phytoestrogen isoflavones on bone density in women: a double-blind, randomized, placebo-controlled trial. American Journal of Clinical Nutrition 79, 326–333.CrossRefGoogle Scholar
Brown, NM, Wang, J, Cotroneo, MS, Zhao, YX, Lamartiniere, CA 1998. Prepubertal genistein treatment modulates TGF-alpha, EGF and EGF-receptor mRNAs and proteins in the rat mammary gland. Molecular and Cellular Endocrinology 144, 149–165.CrossRefGoogle ScholarPubMed
Capuco, AV, Ellis, S, Wood, DL, Akers, RM, Garrett, W 2002. Postnatal mammary ductal growth: three-dimensional imaging of cell proliferation, effects of estrogen treatment, and expression of steroid receptors in prepubertal calves. Tissue & Cell 34, 143–154.CrossRefGoogle ScholarPubMed
Chen, WF, Gao, QG, Wong, MS 2007. Mechanism involved in genistein activation of insulin-like growth factor 1 receptor expression in human breast cancer cells. British Journal of Nutrition 98, 1120–1125.Google Scholar
Drane, HM, Wrathall, AE, Patterson, SP, Hebert, CN 1981. Possible oestrogenic effects of feeding soyameal to prepuberal gilts. British Veterinary Journal 137, 283–288.Google Scholar
Farmer, C, Petit, HV, Weiler, H, Capuco, AV 2007. Effects of dietary supplementation with flax during prepuberty on fatty acid profile, mammogenesis, and bone resorption in gilts. Journal of Animal Science 85, 1675–1686.CrossRefGoogle ScholarPubMed
Farmer, C, Petitclerc, D, Sorensen, MT, Vignola, M, Dourmad, JY 2004. Impacts of dietary protein level and feed restriction during prepuberty on mammogenesis in gilts. Journal of Animal Science 82, 2343–2351.CrossRefGoogle ScholarPubMed
Ford, JA Jr 2003. Estrogenic effects of genistein in ovariectomized gilts. PhD thesis, University of Illinois, IL, USA.Google Scholar
Ford, JA Jr, Clark, SG, Walters, EM, Wheeler, MB, Hurley, WL 2006. Estrogenic effects of genistein on reproductive tissues of ovariectomized gilts. Journal of Animal Science 84, 834–842.CrossRefGoogle ScholarPubMed
Friend, DW, Lodge, GA, Elliot, JI 1981. Effects of energy and dry matter intake on age, body weight and backfat at puberty and on embryo mortality in gilts. Journal of Animal Science 53, 118–124.CrossRefGoogle Scholar
Gu, L, House, SE, Prior, RL, Fang, N, Ronis, MJJ, Clarkson, TB, Wilson, ME, Badger, TM 2006. Metabolic phenotype of isoflavones differ among female rats, pigs, monkeys, and women. Journal of Nutrition 136, 1215–1221.CrossRefGoogle ScholarPubMed
Head, RH, Bruce, NW, Williams, IH 1991. More cells might lead to more milk. In Manipulating pig production III (ed. ES Batterham), p. 76. Australasian Pig Science Association, Attwood, Australia.Google Scholar
Jefferson, WN, Padilla-Banks, E, Newbold, RR 2007. Disruption of the developing female reproductive system by phytoestrogens: genistein as an example. Molecular Nutrition and Food Research 51, 832–844.Google Scholar
Kalbe, C, Mau, M, Rehfeldt, C 2008. Developmental changes and the impact of isoflavones on mRNA expression of IGF-I receptor, EGF receptor and related growth factors in porcine skeletal muscle cell cultures. Growth Hormone & IGF Research 18, 424–433.Google Scholar
Kaludjerovic, J, Ward, WE 2009. Neonatal exposure to daidzen, genistein or the combination modulates bone development in female CD-1 mice. Journal of Nutrition 139, 467–473.CrossRefGoogle ScholarPubMed
Klein, CB, King, AA 2007. Genistein genotoxicity: critical considerations of in vitro exposure dose. Toxicology and Applied Pharmacology 224, 1–11.CrossRefGoogle ScholarPubMed
Kuhn, G, Hennig, U, Kalbe, C, Rehfeldt, C, Ren, MQ, Moors, S, Degen, GH 2004. Growth performance, carcass characteristics and bioavailability of isoflavones in pigs fed soya bean based diets. Archives of Animal Nutrition 58, 265–276.Google Scholar
Labarca, C, Paigen, K 1980. A simple, rapid, and sensitive DNA assay procedure. Analytical Biochemistry 102, 344–352.CrossRefGoogle ScholarPubMed
Lewis, RW, Brooks, N, Milburn, GM, Soames, A, Stone, S, Hall, M, Ashby, J 2003. The effects of the phytoestrogen genistein on the postnatal development of the rat. Toxicological Sciences 71, 74–83.Google Scholar
Li, RW, Capuco, AV 2008. Canonical pathways and networks regulated by estrogen in the bovine mammary gland. Functional & Integrative Genomics 8, 55–68.CrossRefGoogle ScholarPubMed
Lister, CE, Skinner, MA, Hunter, DC 2007. Fruits, vegetables and their phytochemicals for bone and joint health. Current Topics in Nutraceutical Research 5, 67–82.Google Scholar
Luijten, M, Verhoef, A, Dormans, JAMA, Beems, RB, Cremers, HWJM, Nagelkerke, NJD, Adlercreutz, H, Penalvo, JL, Piersma, AH 2007. Modulation of mammary tumor development in Tg.NK (MMTV/c-neu) mice by dietary fatty acids and life stage-specific exposure to phytoestrogens. Reproductive Toxicology 23, 407–413.CrossRefGoogle ScholarPubMed
Mau, M, Kalbe, C, Viergutz, T, Nurnberg, G, Rehfeldt, C 2008. Effects of dietary isoflavones on proliferation and DNA integrity of myoblasts derived from newborn piglets. Pediatric Research 63, 39–45.Google Scholar
Meyer, MJ, Capuco, AV, Boisclair, YR, Van Amburgh, ME 2006. Estrogen-dependent responses of the mammary fat pad in prepubertal dairy heifers. Journal of Endocrinology 190, 819–827.Google Scholar
Moon, YJ, Brazeau, DA, Morris, ME 2007. Effects of flavonoids genistein and biochanin A on gene expression and their metabolism in human mammary cells. Nutrition and Cancer 57, 48–58.Google Scholar
Mundy, GR 2006. Nutritional modulation of bone remodeling during aging. American Journal of Clinical Nutrition 83, 427S–430S.Google Scholar
Murrill, WB, Brown, NM, Zhang, J-X, Manzolillo, PA, Barnes, S, Lamartinière, CA 1996. Prepubertal genistein exposure suppresses mammary cancer and enhances gland differentiation in rats. Carcinogenesis 17, 1451–1457.Google Scholar
Nilsson, S, Mäkelä, S, Treuter, E, Tujague, M, Thomsen, J, Andersson, G, Enmark, E, Pettersson, K, Warner, M, Gustafsson, JA 2001. Mechanisms of estrogen action. Physiological Reviews 81, 1535–1565.Google Scholar
Padilla-Banks, E, Jefferson, WN, Newbold, RR 2006. Neonatal exposure to the phytoestrogen genistein alters mammary gland growth and developmental programming of hormone receptor levels. Endocrinology 147, 4871–4882.CrossRefGoogle Scholar
Pastuszewska, B, Taciak, M, Ochtabinska, A, Tusnio, A, Misztal, T, Romanowicz, K Morawski, A 2008. Nutritional value and physiological effects of soya-free diets fed to rats during growth and reproduction. Journal of Animal Physiology and Animal Nutrition 92, 63–74.Google Scholar
Rachon, D, Menche, A, Vortherms, T, Seidlova-Wuttke, D, Wuttke, W 2008. Effects of dietary equol administration on the mammary gland in ovariectomized Sprague-Dawley rats. Menopause 15, 340–345.CrossRefGoogle ScholarPubMed
Rehfeldt, C, Kalbe, C, Nürnberg, G, Mau, M 2009. Dose-dependent effects of genistein and daidzein on protein metabolism in porcine myotube cultures. Journal of Agricultural Food Chemistry 57, 852–857.Google Scholar
Robert, S, de Passillé, AMB, St-Pierre, N, Dubreuil, P, Pelletier, G, Petitclerc, D, Brazeau, P 1989. Effect of the stress of injection on the serum concentrations of cortisol, prolactin, and growth hormone in gilts and lactating sows. Canadian Journal of Animal Science 69, 663–672.Google Scholar
Rowell, C, Carpenter, DM, Lamartinière, CA 2005. Chemoprevention of breast cancer, proteomic discovery of genistein action in the rat mammary gland. Journal of Nutrition 135, 2953S–2959S.Google Scholar
Ruan, W, Kleinberg, DL 1999. Insulin-like growth factor I is essential for terminal end bud and ductal morphogenesis during mammary development. Endocrinology 140, 5075–5081.CrossRefGoogle ScholarPubMed
Sepehr, E, Robertson, P, Gilani, GS, Cooke, G, Lau, BP-Y 2006. An accurate and reproducible method for the quantitative analysis of isoflavones and their metabolites in rat plasma using liquid chromatography/mass spectrometry combined with photodiode array detection. Journal of AOAC (Association of Official Analytical Chemists) International 89, 1158–1167.Google ScholarPubMed
Setchell, KD, Lydeking-Olsen, E 2003. Dietary phytoestrogens and their effect on bone: evidence from in vitro and in vivo, human observational, and dietary intervention studies. American Journal of Clinical Nutrition 78, 593S–609S.Google Scholar
Sorensen, MT, Farmer, C, Vestergaard, M, Purup, S, Sejrsen, K 2006. Mammary development in prepubertal gilts fed restrictively or ad libitum in two sub-periods between weaning and puberty. Livestock Science 99, 249–255.CrossRefGoogle Scholar
Sorensen, MT, Sejrsen, K, Purup, S 2002. Mammary gland development in gilts. Livestock Production Science 75, 143–148.CrossRefGoogle Scholar
Statistical Analysis Systems Institute (SAS) 1998. SAS/STAT user’s guide (version 6, 4th edition). SAS Institute Inc., Cary, NC, USA.Google Scholar
Stokes, ME, Davis, CS, Koch, GG 1995. Categorical data analysis using the SAS system, 2nd edition. SAS Institute Inc., Cary, NC, USA.Google Scholar
Sun Hwang, C, Seok Kwak, H, Jae Lim, H, Hee Lee, S, Soon Kang, Y, Boo Choe, T, Gil Hur, H, Ok Han, K 2006. Isoflavone metabolites and their in vitro dual functions: they can act as an estrogenic agonist or antagonist depending on the estrogen concentration. Journal of Steroid Biochemistry & Molecular Biology 101, 246–253.Google Scholar
Valentin-Severin, I, Thybaud, V, Le Bon, A-M, Lhuguenot, J-C, Chagnon, M-C 2004. The autoradiographic test for unscheduled DNA synthesis: a sensitive assay for the detection of DNA repair in the HepG2 cell line. Mutation Research 559, 211–217.CrossRefGoogle ScholarPubMed
Warri, A, Saarinen, NM, Makela, S, Hilakivi-Clarke, L 2008. The role of early life genistein exposures in modifying breast cancer risk. British Journal of Cancer 98, 1485–1493.Google Scholar
Weiler, U, Finsler, S, Wehr, U, Claus, R 2001. Comparison of blood markers for the longitudinal monitoring of osteoclastic activity in the pig. Journal of Veterinary Medicine A 48, 609–618.Google Scholar
Williamson, G, Manach, C 2005. Bioavailability and bioefficacy of polyphenols in humans. II. Review of 93 intervention studies. American Journal of Clinical Nutrition 81 (suppl. 1), 243S–255S.CrossRefGoogle ScholarPubMed