Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Benzoic Acid Enhances Embryo Implantation through LIF-Dependent Expression of Integrin αVβ3 and αVβ5

  • Choi, Hee-Jung (School of Korean Medicine and Healthy Aging Korean Medicine Research Center, Pusan National University) ;
  • Chung, Tae-Wook (School of Korean Medicine and Healthy Aging Korean Medicine Research Center, Pusan National University) ;
  • Park, Mi-Ju (School of Korean Medicine and Healthy Aging Korean Medicine Research Center, Pusan National University) ;
  • Kim, Hyung Sik (Laboratory of Molecular Toxicology, School of Pharmacy, SungKyunKwan University) ;
  • You, Sooseong (Korea Institute of Oriental Medicine) ;
  • Lee, Myeong Soo (Korea Institute of Oriental Medicine) ;
  • Joo, Bo Sun (School of Korean Medicine and Healthy Aging Korean Medicine Research Center, Pusan National University) ;
  • Lee, Kyu Sup (Department of Obstetrics and Gynecology, Pusan National University Hospital) ;
  • Kim, Keuk-Jun (Department of Clinical Pathology, DaeKyeung University) ;
  • Wee, Gabbine (Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation) ;
  • Kim, Choong-Yong (Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation) ;
  • Kim, Cheorl-Ho (Department of Biological Science, Sungkyunkwan University) ;
  • Ha, Ki-Tae (School of Korean Medicine and Healthy Aging Korean Medicine Research Center, Pusan National University)
  • Received : 2016.09.19
  • Accepted : 2017.01.09
  • Published : 2017.04.28
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Abstract

Embryo implantation is the crucial step for a successful pregnancy. Diverse factors, including adhesion molecules, growth factors, and cytokines are important for embryo implantation through improving endometrial receptivity. Benzoic acid (BA), a component of various plants, has been shown to have antifungal and antioxidant effects. However, the effect of BA on embryo implantation remains unknown. Here, we showed the contribution of BA for the enhancement of endometrial receptivity through the leukemia inhibitory factor (LIF)-dependent increase of integrin ${\alpha}V$, ${\beta}3$, and ${\beta}5$ expression. Furthermore, in vivo study using a mifepristone-induced implantation failure model showed that BA definitely improves the numbers of implantation embryos. Taken together, we suggest that BA has a novel function for embryo implantation through the up-regulation of LIF-mediated integrins, and may be a candidate for therapeutic medicine to increase the pregnancy rate.

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References

  1. Diedrich K, Fauser BC, Devroey P, Griesinger G. 2007. The role of the endometrium and embryo in human implantation. Hum. Reprod. Update 13: 365-377. https://doi.org/10.1093/humupd/dmm011
  2. Horne AW, White JO, Lalani EN. 2000. The endometrium and embryo implantation. A receptive endometrium depends on more than hormonal influences. BMJ 321: 1301-1302. https://doi.org/10.1136/bmj.321.7272.1301
  3. Koot YE, Macklon NS. 2013. Embryo implantation: biology, evaluation, and enhancement. Curr. Opin. Obstet. Gynecol. 25: 274-279. https://doi.org/10.1097/GCO.0b013e3283630d94
  4. D imitriadis E, Menkhorst E, Salamonsen LA, Paiva P. 2010. Review: LIF and IL11 in trophoblast-endometrial interactions during the establishment of pregnancy. Placenta 31 Suppl: S99-S104. https://doi.org/10.1016/j.placenta.2009.12.027
  5. Cullinan EB, Abbondanzo SJ, Anderson PS, Pollard JW, Lessey BA, Stewart CL. 1996. Leukemia inhibitory factor (LIF) and LIF receptor expression in human endometrium suggests a potential autocrine/paracrine function in regulating embryo implantation. Proc. Natl. Acad. Sci. USA 93: 3115-3120. https://doi.org/10.1073/pnas.93.7.3115
  6. Aghajanova L. 2010. Update on the role of leukemia inhibitory factor in assisted reproduction. Curr. Opin. Obstet. Gynecol. 22: 213-219. https://doi.org/10.1097/GCO.0b013e32833848e5
  7. Wu M , Yin Y, Z hao M, Hu L, C hen Q. 2013. The l ow expression of leukemia inhibitory factor in endometrium: possible relevant to unexplained infertility with multiple implantation failures. Cytokine 62: 334-339. https://doi.org/10.1016/j.cyto.2013.03.002
  8. Steck T, Giess R, Suetterlin MW, Bolland M, Wiest S, Poehls UG, Dietl J. 2004. Leukaemia inhibitory factor (LIF) gene mutations in women with unexplained infertility and recurrent failure of implantation after IVF and embryo transfer. Eur. J. Obstet. Gynecol. Reprod. Biol. 112: 69-73. https://doi.org/10.1016/S0301-2115(03)00315-4
  9. Terakawa J, Wakitani S, Sugiyama M, Inoue N, Ohmori Y, Kiso Y, et al. 2011. Embryo implantation is blocked by intraperitoneal injection with anti-LIF antibody in mice. J. Reprod. Dev. 57: 700-707. https://doi.org/10.1262/jrd.11-048H
  10. Menkhorst E, Zhang JG, Sims NA, Morgan PO, Soo P, Poulton IJ, et al. 2011. Vaginally administered PEGylated LIF antagonist blocked embryo implantation and eliminated non-target effects on bone in mice. PLoS One 6: e19665. https://doi.org/10.1371/journal.pone.0019665
  11. Aschenbach LC, Hester KE, McCann NC, Zhang JG, Dimitriadis E, Duffy DM. 2013. The LIF receptor antagonist PEGLA is effectively delivered to the uterine endometrium and blocks LIF activity in cynomolgus monkeys. Contraception 87: 813-823. https://doi.org/10.1016/j.contraception.2012.09.032
  12. White CA, Zhang JG, Salamonsen LA, Baca M, Fairlie WD, Metcalf D, et al. 2007. Blocking LIF a ction in the u terus by using a PEGylated antagonist prevents implantation: a nonhormonal contraceptive strategy. Proc. Natl. Acad. Sci. USA 104: 19357-19362. https://doi.org/10.1073/pnas.0710110104
  13. Lessey BA, Damjanovich L, Coutifaris C, Castelbaum A, Albelda SM, Buck CA. 1992. Integrin adhesion molecules in the human endometrium. Correlation with the normal and abnormal menstrual cycle. J. Clin. Invest. 90: 188-195. https://doi.org/10.1172/JCI115835
  14. Lessey BA. 1998. Endometrial integrins and the establishment of uterine receptivity. Hum. Reprod. 13 Suppl 3: 247-258; discussion 259-261. https://doi.org/10.1093/humrep/13.suppl_3.247
  15. L essey BA, Castelbaum AJ, Sawin SW, Sun JH. 1995. Integrins as markers of uterine receptivity in women with primary unexplained infertility. Fertil. Steril. 63: 535-542. https://doi.org/10.1016/S0015-0282(16)57422-6
  16. Nair B. 2001. Final report on the safety assessment of benzyl alcohol, benzoic acid, and sodium benzoate. Int. J. Toxicol. 20 Suppl 3: 23-50. https://doi.org/10.1080/10915810152630729
  17. London RE, Gabel SA. 1988. A deuterium surface coil NMR study of the metabolism of D-methionine in the liver of the anesthetized rat. Biochemistry 27: 7864-7869. https://doi.org/10.1021/bi00420a042
  18. Oyanagi K, Kuniya Y, Nagao M, Tsuchiyama A, Nakao T. 1987. Cytotoxicities of sodium benzoate in primary culture of hepatocytes from adult rat liver. Tohoku J. Exp. Med. 152: 47-51. https://doi.org/10.1620/tjem.152.47
  19. Przybyszewski WM, Malec J. 1982. Protection against hydroxyurea-induced cytotoxic effects in L5178Y cells by free radical scavengers. Cancer Lett. 17: 223-228. https://doi.org/10.1016/0304-3835(82)90036-2
  20. Cervantes A, Pinedo HM, Lankelma J, Schuurhuis GJ. 1988. The role of oxygen-derived free radicals in the cytotoxicity of doxorubicin in multidrug resistant and sensitive human ovarian cancer cells. Cancer Lett. 41: 169-177. https://doi.org/10.1016/0304-3835(88)90113-9
  21. Suthanthiran M, Solomon SD, Williams PS, Rubin AL, Novogrodsky A, Stenzel KH. 1984. Hydroxyl radical scavengers inhibit human natural killer cell activity. Nature 307: 276-278. https://doi.org/10.1038/307276a0
  22. Cheung K, Archibald AC, Robinson MF. 1984. Luminol-dependent chemiluminescence produced by neutrophils stimulated by immune complexes. Aust. J. Exp. Biol. Med. Sci. 62: 403-419. https://doi.org/10.1038/icb.1984.39
  23. Walker PD, Shah SV. 1988. Evidence suggesting a role for hydroxyl radical in gentamicin-induced acute renal failure in rats. J. Clin. Invest. 81: 334-341. https://doi.org/10.1172/JCI113325
  24. Evangelista S, Meli A. 1985. Influence of antioxidants and radical scavengers on ethanol-induced gastric ulcers in the rat. Gen. Pharmacol. 16: 285-286. https://doi.org/10.1016/0306-3623(85)90085-0
  25. Chung TW, Kim SJ, Choi HJ, Song KH, Jin UH, Yu DY, et al. 2014. Hepatitis B virus X protein specially regulates the sialyl Lewis A synthesis among glycosylation events for metastasis. Mol. Cancer 13: 222. https://doi.org/10.1186/1476-4598-13-222
  26. Kim EY, Choi HJ, Chung TW, Jang SB, Kim K, Ha KT. 2015. Expression and efficient one-step chromatographic purification of a soluble antagonist for human leukemia inhibitory factor receptor in Escherichia coli. J. Microbiol. Biotechnol. 25: 1307-1314. https://doi.org/10.4014/jmb.1501.01094
  27. Choi HJ, Chung TW, Park MJ, Lee KS, Yoon Y, Kim HS, et al. 2016. Paeonia lactiflora enhances the adhesion of trophoblast to the endometrium via induction of leukemia inhibitory factor expression. PLoS One 11: e0148232. https://doi.org/10.1371/journal.pone.0148232
  28. Brown JK, Shaw JL, Critchley HO, Horne AW. 2012. Human fallopian tube epithelium constitutively expresses integrin endometrial receptivity markers: no evidence for a tubal implantation window. Mol. Hum. Reprod. 18: 111-120. https://doi.org/10.1093/molehr/gar068
  29. Knudtson JF, Tekmal RR, Santos MT, Binkley PA, Krishnegowda N, Valente P, Schenken RS. 2015. Impaired development of early endometriotic lesions in CD44 knockout mice. Reprod. Sci. 23: 87-91.
  30. Zhang Y, Liu S, Liu Y, Wang Z, Wang X, Yan Q. 2009. Overexpression of fucosyltransferase VII (FUT7) promotes embryo adhesion and implantation. Fertil. Steril. 91: 908-914. https://doi.org/10.1016/j.fertnstert.2007.12.012
  31. Chen JR, Cheng JG, Shatzer T, Sewell L, Hernandez L, Stewart CL. 2000. Leukemia inhibitory factor can substitute for nidatory estrogen and is essential to inducing a receptive uterus for implantation but is not essential for subsequent embryogenesis. Endocrinology 141: 4365-4372. https://doi.org/10.1210/endo.141.12.7855
  32. Liang XH, Deng WB, Li M, Zhao ZA, Wang TS, Feng XH, et al. 2014. Egr1 protein acts downstream of estrogen-leukemia inhibitory factor (LIF)-STAT3 pathway and plays a role during implantation through targeting Wnt4. J. Biol. Chem. 289: 23534-23545. https://doi.org/10.1074/jbc.M114.588897
  33. Hu W, Feng Z, Teresky AK, Levine AJ. 2007. p53 regulates maternal reproduction through LIF. Nature 450: 721-724. https://doi.org/10.1038/nature05993
  34. Lubahn DB, Moyer JS, Golding TS, Couse JF, Korach KS, Smithies O. 1993. Alteration of reproductive function but not prenatal sexual development after insertional disruption of the mouse estrogen receptor gene. Proc. Natl. Acad. Sci. USA 90: 11162-11166. https://doi.org/10.1073/pnas.90.23.11162
  35. von Grothusen C, Lalitkumar S, Boggavarapu NR, Gemzell-Danielsson K, Lalitkumar PG. 2014. Recent advances in understanding endometrial receptivity: molecular basis and clinical applications. Am. J. Reprod. Immunol. 72: 148-157. https://doi.org/10.1111/aji.12226
  36. Makker A, Singh MM. 2006. Endometrial receptivity: clinical assessment in relation to fertility, infertility, and antifertility. Med. Res. Rev. 26: 699-746. https://doi.org/10.1002/med.20061
  37. Mains L, Van Voorhis BJ. 2010. Optimizing the technique of embryo transfer. Fertil. Steril. 94: 785-790. https://doi.org/10.1016/j.fertnstert.2010.03.030
  38. Zhang YM, Zhang YY, Bulbul A, Shan X, Wang XQ, Yan Q. 2015. Baicalin promotes embryo adhesion and implantation by upregulating fucosyltransferase IV (FUT4) via Wnt/beta-catenin signaling pathway. FEBS Lett. 589: 1225-1233. https://doi.org/10.1016/j.febslet.2015.04.011
  39. Zhao M, Chang C, Liu Z, Chen LM, Chen Q. 2010. Treatment with low-dose aspirin increased the level LIF and integrin beta3 expression in mice during the implantation window. Placenta 31: 1101-1105. https://doi.org/10.1016/j.placenta.2010.10.002
  40. Chu ng TW, Park MJ, Kim HS, Choi HJ, Ha KT. 2016. Integrin ${\alpha}V{\beta}3$ and ${\alpha}V{\beta}5$ are required for leukemia inhibitory factor-mediated the adhesion of trophoblast cells to the endometrial cells. Biochem. Biophys. Res. Commun. 469: 936-940. https://doi.org/10.1016/j.bbrc.2015.12.103
  41. Agca C, Gubler A, Traber G, Beck C, Imsand C, Ail D, et al. 2013. p38 MAPK signaling acts upstream of LIF-dependent neuroprotection during photoreceptor degeneration. Cell Death Dis. 4: e785. https://doi.org/10.1038/cddis.2013.323
  42. Fan Z, Bau B, Yang H, Aigner T. 2004. IL-1beta induction of IL-6 and LIF in normal articular human chondrocytes involves the ERK, p38 and NFkappaB signaling pathways. Cytokine 28: 17-24. https://doi.org/10.1016/j.cyto.2004.06.003
  43. Carino C, Olawaiye AB, Cherfils S, Serikawa T, Lynch MP, Rueda BR, Gonzalez RR. 2008. Leptin regulation of proangiogenic molecules in benign and cancerous endometrial cells. Int. J. Cancer 123: 2782-2790. https://doi.org/10.1002/ijc.23887
  44. Wu GS. 2004. The functional interactions between the p53 and MAPK signaling pathways. Cancer Biol. Ther. 3: 156-161. https://doi.org/10.4161/cbt.3.2.614
  45. Schneider G, Kramer OH. 2011. NFkappaB/p53 crosstalk - a promising new therapeutic target. Biochim. Biophys. Acta 1815: 90-103.
  46. Abraham AG, O'Neill E. 2014. PI3K/Akt-mediated regulation of p53 in cancer. Biochem. Soc. Trans. 42: 798-803. https://doi.org/10.1042/BST20140070
  47. Feng Z, Zhang C, Kang HJ, Sun Y, Wang H, Naqvi A, et al. 2011. Regulation of female reproduction by p53 and its family members. FASEB J. 25: 2245-2255. https://doi.org/10.1096/fj.10-180166
  48. Yang ZM, Chen DB, Le SP, Harper MJ. 1996. Differential hormonal regulation of leukemia inhibitory factor (LIF) in rabbit and mouse uterus. Mol. Reprod. Dev. 43: 470-476. https://doi.org/10.1002/(SICI)1098-2795(199604)43:4<470::AID-MRD9>3.0.CO;2-M
  49. Arici A, Engin O, Attar E, Olive DL. 1995. Modulation of leukemia inhibitory factor gene expression and protein biosynthesis in human endometrium. J. Clin. Endocrinol. Metab. 80: 1908-1915.
  50. Aghajanova L. 2004. Leukemia inhibitory factor and human embryo implantation. Ann. NY Acad. Sci. 1034: 176-183. https://doi.org/10.1196/annals.1335.020
  51. Danielsson KG, Swahn ML, Bygdeman M. 1997. The effect of various doses of mifepristone on endometrial leukaemia inhibitory factor expression in the midluteal phase - an immunohistochemical study. Hum. Reprod. 12: 1293-1297. https://doi.org/10.1093/humrep/12.6.1293
  52. Lalitkumar PG, Lalitkumar S, Meng CX, Stavreus-Evers A, Hambiliki F, Bentin-Ley U, Gemzell-Danielsson K. 2007. Mifepristone, but not levonorgestrel, inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model. Hum. Reprod. 22: 3031-3037. https://doi.org/10.1093/humrep/dem297
  53. Hazan R, Levine A, Abeliovich H. 2004. Benzoic acid, a weak organic acid food preservative, exerts specific effects on intracellular membrane trafficking pathways in Saccharomyces cerevisiae. Appl. Environ. Microbiol. 70: 4449-4457. https://doi.org/10.1128/AEM.70.8.4449-4457.2004

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