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Effects of different n-6:n-3 fatty acid ratios and of enterolactone on gene expression and PG secretion in bovine endometrial cells

  • Catherine Hallé (a1), Alan K. Goff (a2), Hélène V. Petit (a3), Richard Blouin (a1) and Marie-France Palin (a3)...

Feeding flaxseed to dairy cows can modulate gene expression and PG synthesis in the uterus at the time of peri-implantation. The objectives of the present study were to determine which flaxseed components are responsible for these effects and how different endometrial cell types are affected. We evaluated the effects of six different linoleic acid (n-6):α-linolenic acid (n-3) ratios and three concentrations of the lignan enterolactone (ENL) on endometrial stromal cells (SC) and epithelial cells (EC). The mRNA abundance of genes with known or suspected roles in embryo survival or PG synthesis was evaluated, along with PGE2 and PGF concentrations in culture media. The mRNA abundance of several genes was modulated by different fatty acid (FA) ratios and/or ENL, and this modulation differed between cell types. The FA4 (FA at an n-6:n-3 ratio of 4) treatment (rich in n-3 FA) increased the mRNA abundance of genes that have positive effects on uterine receptivity and implantation when compared with the FA25 (FA at an n-6:n-3 ratio of 25) treatment (rich in n-6 FA). ENL decreased PGE2 and PGF concentrations in both cell types, and this reduction was associated with lower mRNA abundance of the PG synthase genes AKR1B1 and PTGES in SC. The combination of ENL with FA (FA4 treatment) resulted in the greatest reduction in PGF concentrations when compared with the addition of FA (FA4) or ENL alone. Because of the known luteolytic properties of PGF, a reduction in endometrial PGF secretion would favour the establishment and maintenance of pregnancy.

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      Effects of different n-6:n-3 fatty acid ratios and of enterolactone on gene expression and PG secretion in bovine endometrial cells
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* Corresponding author: M.-F. Palin, fax +1 819 564 5507, email
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1 Spencer, TE, Burghardt, RC, Johnson, GA, et al. (2004) Conceptus signals for establishment and maintenance of pregnancy. Anim Reprod Sci 82–83, 537550.
2 Bazer, FW, Spencer, TE & Ott, TL (1997) Interferon τ: a novel pregnancy recognition signal. Am J Reprod Immunol 37, 412420.
3 Spencer, TE, Johnson, GA, Bazer, FW, et al. (2007) Pregnancy recognition and conceptus implantation in domestic ruminants: roles of progesterone, interferons and endogenous retroviruses. Reprod Fertil Dev 19, 6578.
4 Xiao, CW, Murphy, BD, Sirois, J, et al. (1999) Down-regulation of oxytocin-induced cyclooxygenase-2 and prostaglandin F synthase expression by interferon-τ in bovine endometrial cells. Biol Reprod 60, 656663.
5 Arosh, JA, Banu, SK, Kimmins, S, et al. (2004) Effect of interferon-τ on prostaglandin biosynthesis, transport, and signaling at the time of maternal recognition of pregnancy in cattle: evidence of polycrine actions of prostaglandin E2 . Endocrinology 145, 52805293.
6 Parent, J, Chapdelaine, P, Sirois, J, et al. (2002) Expression of microsomal prostaglandin E synthase in bovine endometrium: coexpression with cyclooxygenase type 2 and regulation by interferon-τ. Endocrinology 143, 29362943.
7 Pratt, BR, Butcher, RL & Inskeep, EK (1977) Antiluteolytic effect of the conceptus and of PGE2 in ewes. J Anim Sci 45, 784791.
8 Lewis, CS & Waterman, RN (1985) Metabolism of arachidonic acid in vitro by ovine conceptuses recovered during early pregnancy. Prostaglandins 30, 263283.
9 Mattos, R, Staples, CR & Thatcher, WW (2000) Effects of dietary fatty acids on reproduction in ruminants. Rev Reprod 5, 3845.
10 Schmitz, G & Ecker, J (2008) The opposing effects of n-3 and n-6 fatty acids. Prog Lipid Res 47, 147155.
11 Mattos, R, Guzeloglu, A, Badinga, L, et al. (2003) Polyunsaturated fatty acids and bovine interferon-τ modify phorbol ester-induced secretion of prostaglandin F and expression of prostaglandin endoperoxide synthase-2 and phospholipase-A2 in bovine endometrial cells. Biol Reprod 69, 780787.
12 Lessard, M, Gagnon, N & Petit, HV (2003) Immune response of postpartum dairy cows fed flaxseed. J Dairy Sci 86, 26472657.
13 Robinson, RS, Pushpakumara, PG, Cheng, Z, et al. (2002) Effects of dietary polyunsaturated fatty acids on ovarian and uterine function in lactating dairy cows. Reproduction 124, 119131.
14 Coyne, GS, Kenny, DA, Childs, S, et al. (2008) Dietary n-3 polyunsaturated fatty acids alter the expression of genes involved in prostaglandin biosynthesis in the bovine uterus. Theriogenology 70, 772782.
15 Waters, SM, Childs, S, Sreenan, JM, et al. (2007) Effect of dietary polyunsaturated fatty acids on uterine endometrial gene expression of enzymes involved in prostaglandin biosynthesis in cattle. In Proceedings of Irish Agricultural Research Forum, March, Tullamore, Ireland , pp. 27.
16 Bilby, TR, Guzeloglu, A, MacLaren, LA, et al. (2006) Pregnancy, bovine somatotropin, and dietary n-3 fatty acids in lactating dairy cows: II. Endometrial gene expression related to maintenance of pregnancy. J Dairy Sci 89, 33753385.
17 Ambrose, DJ, Kastelic, JP, Corbett, R, et al. (2006) Lower pregnancy losses in lactating dairy cows fed a diet enriched in α-linolenic acid. J Dairy Sci 89, 30663074.
18 Petit, HV, Germiquet, C & Lebel, D (2004) Effect of feeding whole, unprocessed sunflower seeds and flaxseed on milk production, milk composition, and prostaglandin secretion in dairy cows. J Dairy Sci 87, 38893898.
19 Petit, HV & Twagiramungu, H (2006) Conception rate and reproductive function of dairy cows fed different fat sources. Theriogenology 66, 13161324.
20 Petit, HV & Benchaar, C (2007) Milk production, milk composition, blood composition, and conception rate of transition dairy cows fed different profiles of fatty acids. Can J Anim Sci 87, 591600.
21 Gagnon, N, Cortes, C, da Silva, D, et al. (2009) Ruminal metabolism of flaxseed (Linum usitatissimum) lignans to the mammalian lignan enterolactone and its concentration in ruminal fluid, plasma, urine and milk of dairy cows. Br J Nutr 102, 10151023.
22 Landete, JM (2012) Plant and mammalian lignans: a review of source, intake, metabolism, intestinal bacteria and health. Food Res Int 46, 410424.
23 Bauersachs, S, Mitko, K, Ulbrich, SE, et al. (2008) Transcriptome studies of bovine endometrium reveal molecular profiles characteristic for specific stages of estrous cycle and early pregnancy. Exp Clin Endocrinol Diabetes 116, 371384.
24 Bauersachs, S, Ulbrich, SE, Gross, K, et al. (2006) Embryo-induced transcriptome changes in bovine endometrium reveal species-specific and common molecular markers of uterine receptivity. Reproduction 132, 319331.
25 Klein, C, Bauersachs, S, Ulbrich, SE, et al. (2006) Monozygotic twin model reveals novel embryo-induced transcriptome changes of bovine endometrium in the preattachment period. Biol Reprod 74, 253264.
26 Palin, MF, Beaudry, D, Vallée, M, et al. (2009) Development of a two-species cDNA microarray for transcriptional profiling of sow and dairy cow reproductive traits. J Anim Sci 91, 476477.
27 Palin, MF, Brochu-Gaudreau, K & Small, JA, et al. (2006) Use of subtractive hybridization to identify genes affected by omega 3 fatty acids in day 17 embryos and endometrial tissues. In Proceedings of the 8th World Congress on Genetics Applied to Livestock Production, 13–18 August 2006, Belo Horizonte, Minas Gerais, Brazil, pp. 11–12.
28 Short, EC Jr, Geisert, RD, Helmer, SD, et al. (1991) Expression of antiviral activity and induction of 2′,5′-oligoadenylate synthetase by conceptus secretory proteins enriched in bovine trophoblast protein-1. Biol Reprod 44, 261268.
29 Pru, JK, Austin, KJ, Haas, AL, et al. (2001) Pregnancy and interferon-τ upregulate gene expression of members of the 1–8 family in the bovine uterus. Biol Reprod 65, 14711480.
30 Zhang, H & Lai, Q (2004) Transcription and translation of dickkopf-1 in endometrium of pregnant mice during the peri-implantation period. J Huazhong Univ Sci Technolog Med Sci 24, 625627, 638.
31 Stumpo, DJ, Byrd, NA, Phillips, RS, et al. (2004) Chorioallantoic fusion defects and embryonic lethality resulting from disruption of Zfp36L1, a gene encoding a CCCH tandem zinc finger protein of the Tristetraprolin family. Mol cell biol 24, 64456455.
32 Fortier, MA, Guilbault, LA & Grasso, F (1988) Specific properties of epithelial and stromal cells from the endometrium of cows. J Reprod Fertil 83, 239248.
33 Ireland, JJ, Murphee, RL & Coulson, PB (1980) Accuracy of predicting stages of bovine estrous cycle by gross appearance of the corpus luteum. J Dairy Sci 63, 155160.
34 Arosh, JA, Parent, J, Chapdelaine, P, et al. (2002) Expression of cyclooxygenases 1 and 2 and prostaglandin E synthase in bovine endometrial tissue during the estrous cycle. Biol Reprod 67, 161169.
35 Xiao, CW & Goff, AK (1998) Differential effects of oestradiol and progesterone on proliferation and morphology of cultured bovine uterine epithelial and stromal cells. J Reprod Fertil 112, 315324.
36 Ramsay, TG (2001) Porcine leptin alters insulin inhibition of lipolysis in porcine adipocytes in vitro . J Anim Sci 79, 653657.
37 Arnold, JT, Kaufman, DG, Seppälä, M, et al. (2001) Endometrial stromal cells regulate epithelial cell growth in vitro: a new co-culture model. Hum Reprod 16, 836845.
38 Kleinman, HK & Martin, GR (2005) Matrigel: basement membrane matrix with biological activity. Semin Cancer Biol 15, 378386.
39 Mackintosh, SB, Schubert, HJ, Healy, LL, et al. (2013) Polarised bovine endometrial epithelial cells vectorially secrete prostaglandins and chemotactic factors under physiological and pathological conditions. Reproduction 145, 5772.
40 Caldari-Torres, C, Rodriguez-Sallaberry, C, Greene, ES, et al. (2006) Differential effects of n-3 and n-6 fatty acids on prostaglandin F2α production by bovine endometrial cells. J Dairy Sci 89, 971977.
41 Paupoo, AAV, Zhu, ZB, Wang, M, et al. (2010) A conditionally replicative adenovirus, CRAd-S-pK7, can target endometriosis with a cell-killing effect. Hum Reprod 25, 20682083.
42 Parent, J, Villeneuve, C, Alexenko, AP, et al. (2003) Influence of different isoforms of recombinant trophoblastic interferons on prostaglandin production in cultured bovine endometrial cells. Biol Reprod 68, 10351043.
43 Weems, CW, Lee, CN, Weems, YS, et al. (1988) Distribution of progesterone to the uterus and associated vasculature of cattle. Endocrinol Jpn 35, 625630.
44 Guzeloglu, A, Michel, F & Thatcher, WW (2004) Differential effects of interferon-τ on the prostaglandin synthetic pathway in bovine endometrial cells treated with phorbol ester. J Dairy Sci 87, 20322041.
45 Farmer, C, Palin, MF, Gilani, GS, et al. (2010) Dietary genistein stimulates mammary hyperplasia in gilts. Animal 4, 454465.
46 Applied Biosystems (1997) User Bulletin No. 2: ABI PRISM 7700 Sequence Detection System. Applied Biosystems, Foster City, CA, USA..
47 Vandesompele, J, De Preter, K, Pattyn, F, et al. (2002) Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol 3, RESEARCH0034.
48 Gray, CA, Abbey, CA, Beremand, PD, et al. (2006) Identification of endometrial genes regulated by early pregnancy, progesterone, and interferon τ in the ovine uterus. Biol Reprod 74, 383394.
49 Mansouri-Attia, N, Aubert, J, Reinaud, P, et al. (2009) Gene expression profiles of bovine caruncular and intercaruncular endometrium at implantation. Physiol Genomics 39, 1427.
50 Hansen, TR, Austin, KJ & Johnson, GA (1997) Transient ubiquitin cross-reactive protein gene expression in the bovine endometrium. Endocrinology 138, 50795082.
51 Schmitt, RA, Geisert, RD, Zavy, MT, et al. (1993) Uterine cellular changes in 2′,5′-oligoadenylate synthetase during the bovine estrous cycle and early pregnancy. Biol Reprod 48, 460466.
52 Fladeby, C, Gupta, SN, Barois, N, et al. (2008) Human PARM-1 is a novel mucin-like, androgen-regulated gene exhibiting proliferative effects in prostate cancer cells. Int J Cancer 122, 12291235.
53 Yeon, PJ, Jang, H, Curry, TE, et al. (2013) Prostate androgen-regulated mucin-like protein1: a novel regulator of progesterone metabolism. Mol Endocrinol 27, 18711886.
54 Xiao, CW, Liu, JM, Sirois, J, et al. (1998) Regulation of cyclooxygenase-2 and prostaglandin F synthase gene expression by steroid hormones and interferon-τ in bovine endometrial cells. Endocrinology 139, 22932299.
55 Ulbrich, SE, Meyer, SU, Zitta, K, et al. (2011) Bovine endometrial metallopeptidases MMT14 and MMP2 and the metallopeptidase inhibitor TIMP2 participate in maternal preparation of pregnancy. Mol Cell Endocrinol 332, 4857.
56 Grant-Tschudy, KS & Wira, CR (2005) Hepatocyte growth factor regulation of uterine epithelial cell transepithelial resistance and tumor necrosis factor α release in culture. Biol Reprod 72, 814821.
57 Cheng, Z, Robinson, RS, Pushpakumara, PGA, et al. (2001) Effect of dietary polyunsaturated fatty acids on uterine prostaglandin synthesis in the cow. J Endocrinol 171, 463473.
58 Cheng, Z, Elmes, M, Kirkup, SE, et al. (2004) Alteration of prostaglandin production and agonist responsiveness by n-6 polyunsaturated fatty acids in endometrial cells from late-gestation ewes. J Endocrinol 182, 249256.
59 Cheng, Z, Abayasekara, DRE, Ward, F, et al. (2013) Altering n-3 to n-6 polyunsaturated fatty acid ratios affects prostaglandin production by ovine uterine endometrium. Anim Reprod Sci 143, 3847.
60 Wathes, DC, Abayasekara, DR & Aitken, RJ (2007) Polyunsaturated fatty acids in male and female reproduction. Biol Reprod 77, 190201.
61 Imakawa, K, Nagaoka, K, Nojima, H, et al. (2005) Changes in immune cell distribution an IL-10 production are regulated through endometrial IP-10 expression in the goat uterus. Am J Reprod Immunol 53, 5464.
62 Omoto, Y, Lathe, R, Warner, M, et al. (2005) Early onset of puberty and early ovarian failure in CYP7B1 knockout mice. Proc Natl Acad Sci U S A 102, 28142819.
63 Henricks, DM, Dickey, JF, Hill, JR, et al. (1972) Plasma estrogen and progesterone levels after mating, and during late pregnancy and postpartum in cows. Endocrinology 90, 13361342.
64 Abayasekara, DR & Wathes, DC (1999) Effects of altering dietary fatty acid composition on prostaglandin synthesis and fertility. Prostaglandins Leukot Essent Fatty Acids 61, 275287.
65 Adlercreutz, H & Mazur, W (1997) Phyto-oestrogens and Western diseases. Ann Med 29, 95120.
66 Lampe, JW, Atkinson, C & Hullar, MA (2006) Assessing exposure to lignans and their metabolites in humans. J AOAC Int 89, 11741181.
67 Zhou, W, Wang, G, Han, Z, et al. (2009) Metabolism of flaxseed lignans in the rumen and its impact on ruminal metabolism and flora. Anim Feed Sci Technol 150, 1826.
68 Prasad, K (2000) Antioxidant activity of secoisolariciresinol diglucoside-derived metabolites, secoisolariciresinol, enterodiol, and enterolactone. Int J Angiol 9, 220225.
69 Petit, HV, Small, JA, Palin, MF, et al. (2007) Effects of flaxseed supplementation on endometrial expression of ISG17 and intrauterine prostaglandin concentrations in primiparous dairy cows submitted to GnRH-based synchronized ovulation. Can J Anim Sci 87, 343352.
70 Fleming, JGW, Song, G, Choi, Y, et al. (2009) Interferon regulatory factor 6 (IRF6) is expressed in the ovine uterus and functions as a transcriptional activator. Mol cell Endocrinol 299, 252260.
71 Bell, SE, Sanchez, MJ, Spasic-Boskovic, O, et al. (2006) The RNA binding protein Zfp36l1 is required for normal vascularisation and post-transcriptionally regulates VEGF expression. Dev Dyn 235, 31443155.
72 Zakrzewska, E, Madore, E & Chapdelaine, P, et al. (2005) Downregulation of AKR1B1 and MPGES1 by RNA silencing reduces prostaglandin production in human endometrial cells. In Annual Meeting, Society for the Study of Reproduction: Biology of Reproduction, Special Issue: M760 (Abstract)..
73 Parent, J & Fortier, MA (2005) Expression and contribution of three different isoforms of prostaglandin E synthase in the bovine endometrium. Biol Reprod 73, 3644.
74 Parent, J, Villeneuve, C & Fortier, MA (2003) Evaluation of the contribution of cyclooxygenase 1 and cyclooxygenase 2 to the production of PGE2 and PGF in epithelial cells from bovine endometrium. Reproduction 126, 539547.
75 Thatcher, WW, Guzeloglu, A, Mattos, R, et al. (2001) Uterine–conceptus interactions and reproductive failure in cattle. Theriogenology 56, 14351450.
76 Ringbom, T, Huss, U, Stenholm, A, et al. (2001) Cox-2 inhibitory effects of naturally occurring and modified fatty acids. J Nat Prod 64, 745749.
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