DOI QR코드

DOI QR Code

단백체학과 생물정보학을 이용한 자궁 내 환경의 이해

Understanding of Intrauterine Environment Changes based on Proteomics and Bioinformatics during Estrous Cycle

  • 이상희 (타즈매니아대학교 기술환경디자인대학 ICT학과) ;
  • 이승형 (강원대학교 동물생명과학대학)
  • Lee, Sang-Hee (Discipline of ICT, School of Technology, Environments and Design, University of Tasmania) ;
  • Lee, Seunghyung (College of Animal Life Sciences, Kangwon National University)
  • 투고 : 2019.04.30
  • 심사 : 2019.05.21
  • 발행 : 2019.05.30

초록

암컷의 자궁에서 일어나는 수정은 새로운 생명의 시작점이다. 암컷의 번식기관은 난소, 난관, 자궁, 자궁경부 및 질로 구성되어 있으며, 이들기관은 발정주기에 따라 생리학적인 역할이 조절된다. 자궁은 수정란의 발달과 착상이 이루어지는 곳이기 때문에, 수정란과 자궁 환경의 상호작용은 안정적인 임신을 위한 필수적인 조건으로 알려져있다. 자궁내막은 자궁의 한 부분으로써 이들의 형태학적인 특징은 호르몬에 의해 반복적으로 변화되며, 자궁내막으로부터 분비되는 자궁액 역시 그 특징이 변화하게 된다. 최근, 자궁내막 및 자궁액 내 포함된 대량의 단백질을 단백체학과 생물정보학의 발전에 따라 검출할 수 있게 되었으며, 이러한 기술에 의해 번식학 발전을 가속화하고 있다. 대량의 단백질 정보는 성호르몬 신호기전 및 혈관신생과 같은 이론 등을 깊게 연구할 수 있는 도구로써 이용되고 있다. 본 총설에서는 자궁내막의 재구성, 자궁선 및 자궁액에 대한 기초적인 생물학적인 지식을 바탕으로, 단백체학과 생물정보학을 활용한 자궁내막 및 자궁액 연구에 대해서 소개하고자 한다. 또한, 생물정보학 도구를 활용하여 단백체학에서 탐색된 자궁내막 및 자궁액 관련 단백질들의 상호작용 알아보는 방법에 대해서도 소개하였다. 따라서, 본 총설의 내용은 발정주기동안 자궁내막 안에서 일어나는 새로운 세포 신호기전을 탐색하는데 큰 도움이 될것이라 생각된다.

Fertilization is the beginning of a new life that occurs in the female uterine. The female reproductive tract is composed ovary, oviduct, uterine, vagina and cervix, their physiological features are regulated by estrous cycle. Of these, uterine is a main point to establish embryo development and implantation, and intercommunication between embryo and uterine environment is necessary for suitable pregnancy. Endometrium is part of the uterine, its morphology is repetitively changed by hormones, and characteristic of uterine fluid from endometrium is also changed. Recently, massive proteins of endometrium and uterine fluid can be detected according to develop proteomics and bioinformatics and have been accelerated the understanding of the reproductive biology fields. Moreover, the massive protein information is actively studying with deeply studied theory such as sex hormone signal pathway and angiogenesis in mammals. In this paper, we review understanding of endometrium remodeling, uterine gland and fluid during estrous cycle, additionally studies on endometrium and uterine fluid based on proteomics techniques. Lastly, we introduced methods of the protein-protein correlation using bioinformatics tool that interaction with hormone receptors, representative angiogenetic factors and detected proteins using proteomics in endometrium and uterine fluid. This review will be useful to understanding the study on search of new cell mechanism in endometrium and uterine fluid.

키워드

SMGHBM_2019_v29n5_621_f0001.png 이미지

Fig. 1. Images of the ovary (A-D) and uterus (E-H) morphology during estrous cycle in sows.

SMGHBM_2019_v29n5_621_f0002.png 이미지

Fig. 2. Sixteen proteins interaction among progesterone receptor (PGR), estrogen receptor alpha (ESR1), myoglobin (MB), vascular endothelial grwoth factor D (VEGFD), vinculin (VCL), actin beta (ACTB), annexin A4 (ANXA4), haptoglobin (HP), metalloproteinase inhibitor (TIMP1), coatomer subunit gamma-2 (COPG2), alpha-enolase (ENO1), annexin A2 (ANXA2), VEGFA, VEGFR2 (KDR), angiopoetin 2 (ANGPT1) and Tie2, protein-protein interaction was STING database, protein interaction with only sixteen protein (a) and added network nodes based on STRING database (b), Red cycle indicate that paxillin (PXN), the protein was conneted between angiogenetic proteins (VEGFA, KDR) and cytoskeleton protein (VCL).

Table 1. Biological process and molecular funtion of estrous cycle-associated proteins

SMGHBM_2019_v29n5_621_t0001.png 이미지

참고문헌

  1. Araujo, V. R., Duarte, A. B. G., Bruno, J. B., Pinho Lopes, C. A. and de Figueiredo, J. R. 2013. Importance of vascular endothelial growth factor (VEGF) in ovarian physiology of mammals. Zygote 21, 295-304. https://doi.org/10.1017/S0967199411000578
  2. Bailey, D. W., Dunlap, K. A., Frank, J. W., Erikson, D. W., White, B. G., Bazer, F. W., Burghardt, R. C. and Johnson, G. A. 2010. Effects of long-term progesterone on developmental and functional aspects of porcine uterine epithelia and vasculature: progesterone alone does not support development of uterine glands comparable to that of pregnancy. Reproduction 140, 583. https://doi.org/10.1530/REP-10-0170
  3. Bazer, F. W. and Johnson, G. A. 2014. Pig blastocyst-uterine interactions. Differentiation 87, 52-65. https://doi.org/10.1016/j.diff.2013.11.005
  4. Bazer, F. W., Song, G., Kim, J., Dunlap, K. A., Satterfield, M. C., Johnson, G. A., Burghardt, R. C. and Wu, G. 2012. Uterine biology in pigs and sheep. J. Anim. Sci. Biotechnol. 3, 1-23. https://doi.org/10.1186/2049-1891-3-1
  5. Bowen, J. A., Bazer, F. W. and Burghardt, R. C. 1996. Spatial and temporal analyses of integrin and Muc-1 expression in porcine uterine epithelium and trophectoderm in vivo. Biol. Reprodu. 55, 1098-1106. https://doi.org/10.1095/biolreprod55.5.1098
  6. Burghardt, R. C., Johnson, G. A., Jaeger, L. A., Ka, H., Garlow, J. E., Spencer, T. E. and Bazer, F. W. 2002. Integrins and extracellular matrix proteins at the maternal-fetal interface in domestic animals. Cells Tissues Organs 172, 202-217. https://doi.org/10.1159/000066969
  7. Chae, J.-I., Kim, J., Lee, S. G., Jeon, Y. J., Kim, D. W., Soh, Y., Seo, K. S., Lee, H. K., Choi, N. J. and Ryu, J. 2011. Proteomic analysis of pregnancy-related proteins from pig uterus endometrium during pregnancy. Proteome Sci. 9, 41. https://doi.org/10.1186/1477-5956-9-41
  8. Croxatto, H. B., Devoto, L., Durand, M., Ezcurra, E., Larrea, F., Nagle, C., Ortiz, M. E., Vantman, D., Vega, M. and Von Hertzen, H. 2001. Mechanism of action of hormonal preparations used for emergency contraception: a review of the literature. Contraception 63, 111-121. https://doi.org/10.1016/S0010-7824(01)00184-6
  9. Diao, H., Aplin, J. D., Xiao, S., Chun, J., Li, Z., Chen, S. and Ye, X. 2011. Altered spatiotemporal expression of collagen types I, III, IV, and VI in Lpar3-deficient peri-implantation mouse uterus. Biol. Reprod. 84, 255-265. https://doi.org/10.1095/biolreprod.110.086942
  10. Gaengel, K., and Betsholtz, C. 2013. Endocytosis regulates VEGF signalling during angiogenesis. Nat. Cell Biol. 15, 233-235. https://doi.org/10.1038/ncb2705
  11. Geisert, R., Pratt, T. N., Bazer, F. W., Mayes, J. S. and Watson, G. H. 1994. Immunocytochemical localization and changes in endometrial progestin receptor protein during the porcine oestrous cycle and early pregnancy. Reprod. Fertil. Dev. 6, 749-760. https://doi.org/10.1071/RD9940749
  12. Gray, C. A., Abbey, C. A., Beremand, P. D., Choi, Y., Farmer, J. L., Adelson, D. L., Thomas, T. L., Bazer, F. W. and Spencer, T. E. 2006. Identification of endometrial genes regulated by early pregnancy, progesterone and interferon tau in the ovine uterus. Biol. Reprod. 74, 383-394. https://doi.org/10.1095/biolreprod.105.046656
  13. Gray, C. A., Bartol, F. F., Tarleton, B. J., Wiley, A. A., Johnson, G. A., Bazer, F. W. and Spencer, T. E. 2001. Developmental biology of uterine glands. Biol. Reprod. 65, 1311-1323. https://doi.org/10.1095/biolreprod65.5.1311
  14. Herbert, C. and Trigg, T. 2005. Applications of GnRH in the control and management of fertility in female animals. Anim. Reprod. Sci. 88, 141-153. https://doi.org/10.1016/j.anireprosci.2005.05.007
  15. Hettinger, A. M., Allen, M. R., Zhang, B. R., Goad, D. W., Malayer, J. R. and Geisert, R. D. 2001. Presence of the acute phase protein, bikunin, in the endometrium of gilts during estrous cycle and early pregnancy. Biol. Reprod. 65, 507-513. https://doi.org/10.1095/biolreprod65.2.507
  16. Hyder, S. M. and Stancel, G. 2000. Regulation of VEGF in the reproductive tract by sex-steroid hormones. Histol. Histopathol. 15, 325-334.
  17. Jalali, B. M., Bogacki, M., Dietrich, M., Likszo, P. and Wasielak, M. 2015. Proteomic analysis of porcine endometrial tissue during peri-implantation period reveals altered protein abundance. J. Proteomics 125, 76-88. https://doi.org/10.1016/j.jprot.2015.05.003
  18. Jeong, J. W., Kwak, I., Lee, K. Y., Kim, T. H., Large, M. J., Stewart, C. L., Kaestner, K. H., Lydon, J. P. and DeMayo, F. J. 2010. Foxa2 is essential for mouse endometrial gland development and fertility. Biol. Reprod. 83, 396-403. https://doi.org/10.1095/biolreprod.109.083154
  19. Kaczmarek, M., Blitek, A., Schams, D. and Ziecik, A. 2010. Effect of luteinizing hormone and tumour necrosis factoralpha on VEGF secretion by cultured porcine endometrial stromal cells. Reprod. Dom. Anim. 45, 481-486. https://doi.org/10.1111/j.1439-0531.2008.01266.x
  20. Kaczmarek, M., Kiewisz, J., Schams, D. and Ziecik, A. 2009. Expression of VEGF-receptor system in conceptus during peri-implantation period and endometrial and luteal expression of soluble VEGFR-1 in the pig. Theriogenology 71, 1298-1306. https://doi.org/10.1016/j.theriogenology.2008.12.022
  21. Kayser, J. P. R., Kim, J. G., Cerny, R. L. and Vallet, J. L. 2006. Global characterization of porcine intrauterine proteins during early pregnancy. Reproduction 131, 379-388. https://doi.org/10.1530/rep.1.00882
  22. Khan, A., Sharma, D., Faheem, M., Bisht, D. and Khan, A. U. 2017. Proteomic analysis of a carbapenem-resistant Klebsiella pneumoniae strain in response to meropenem stress. J. Glob. Antimicrob. Resist. 8, 172-178. https://doi.org/10.1016/j.jgar.2016.12.010
  23. Khansarizadeh, M., Mokhtarzadeh, A., Rashedinia, M., Taghdisi, S., Lari, P., Abnous, K. and Ramezani, M. 2016. Identification of possible cytotoxicity mechanism of polyethylenimine by proteomics analysis. Hum. Exp. Toxicol. 35, 377-387. https://doi.org/10.1177/0960327115591371
  24. Lash, G. E., Innes, B. A., Drury, J. A., Robson, S. C., Quenby, S. and Bulmer, J. N. 2011. Localization of angiogenic growth factors and their receptors in the human endometrium throughout the menstrual cycle and in recurrent miscarriage. Hum. Reprod. 376,183-195.
  25. Lee, S. H., Song, E. J., Hwangbo, Y., Lee, S. and Park, C. K. 2016. Change of uterine histroph proteins during follicular and luteal phase in pigs. Anim. Reprod. Sci. 168, 26-33. https://doi.org/10.1016/j.anireprosci.2016.02.022
  26. Lee, S., Lee, S. H., Yang, B. K. and Park, C. K. 2017. The expression of VEGF, myoglobin and CRP2 proteins regulating endometrial remodeling in the porcine endometrial tissues during follicular and luteal phase. Anim. Sci. J. 88, 1291-1297. https://doi.org/10.1111/asj.12774
  27. Lin, H., Wang, X., Liu, G., Fu, J. and Wang, A. 2007. Expression of ${\alpha}$V and ${\beta}$3 integrin subunits during implantation in pig. Mol. Reprod. Dev. 74, 1379-1385. https://doi.org/10.1002/mrd.20732
  28. Lucifero, D., Chaillet, J. R. and Trasler, J. M. 2004. Potential significance of genomic imprinting defects for reproduction and assisted reproductive technology. Hum. Reprod. Update 10, 3-18. https://doi.org/10.1093/humupd/dmh002
  29. Luczak, M., Formanowicz, D., Marczak, Ł., Pawliczak, E., Wanic-Kossowska, M., Figlerowicz, M. and Stobiecki, M. 2015. Deeper insight into chronic kidney disease-related atherosclerosis: comparative proteomic studies of blood plasma using 2DE and mass spectrometry. J. Transl. Med. 13, 20. https://doi.org/10.1186/s12967-014-0378-8
  30. Macrae, C. N., Alnwick, K. A., Milne, A. B. and Schloerscheidt, A. M. 2002. Person perception across the menstrual cycle: Hormonal influences on social-cognitive functioning. Psychol. Sci. 13, 532-536. https://doi.org/10.1111/1467-9280.00493
  31. Maliqueo, M., Echiburu, B. and Crisosto, N. 2016. Sex steroids modulate uterine-placental vasculature: implications for obstetrics and neonatal outcomes. Front. Physiol. 7, 152.
  32. Mann, G. 2009. Corpus luteum size and plasma progesterone concentration in cows. Anim. Reprod. Sci. 115, 296-299. https://doi.org/10.1016/j.anireprosci.2008.11.006
  33. Niswender, G. D., Juengel, J. L., Silva, P. J., Rollyson, M. K. and McIntush, E. W. 2000. Mechanisms controlling the function and life span of the corpus luteum. Physiol. Rev. 80, 1-29. https://doi.org/10.1152/physrev.2000.80.1.1
  34. Parmar, T., Sachdeva, G., Savardekar, L., Katkam, R., Nimbkar-Joshi, S., Gadkar-Sable, S., Salvi, V., Manjramkar, D., Meherji, P. and Puri, C. 2007. Protein repertoire of human uterine fluid duringthe mid-secretory phase of the menstrual cycle. Hum. Reprod. 23, 379-386. https://doi.org/10.1093/humrep/dem367
  35. Reddy, U. M., Wapner, R. J., Rebar, R. W. and Tasca, R. J. 2007. Infertility, assisted reproductive technology, and adverse pregnancy outcomes: executive summary of a National Institute of Child Health and Human Development workshop. Obstet. Gynecol. 109, 967-977. https://doi.org/10.1097/01.AOG.0000259316.04136.30
  36. Schams, D. and Berisha, B. 2004. Regulation of corpus luteum function in cattle-an overview. Reprod. Dom. Anim. 39, 241-251. https://doi.org/10.1111/j.1439-0531.2004.00509.x
  37. Schatz, F., Guzeloglu-Kayisli, O., Arlier, S., Kayisli, U. A. and Lockwood, C. J. 2016. The role of decidual cells in uterine hemostasis, menstruation, inflammation, adverse pregnancy outcomes and abnormal uterine bleeding. Hum. Reprod. Update 22, 497-515. https://doi.org/10.1093/humupd/dmw004
  38. Spencer, T. E. and Bazer, F. W. 2002. Biology of progesterone action during pregnancy recognition and maintenance of pregnancy. Front. Biosci. 7, d1879-d1898. https://doi.org/10.2741/A886
  39. Spencer, T. E. and Bazer, F. W. 2004. Conceptus signals for establishment and maintenance of pregnancy. Reprod. Biol. Endocrinol. 2, 49. https://doi.org/10.1186/1477-7827-2-49
  40. Taylor, K. M., Gray, C. A., Joyce, M. M., Stewart, M. D., Bazer, F. W. and Spencer, T. E. 2000. Neonatal ovine uterine development involves alterations in expression of receptors for estrogen, progesterone, and prolactin. Biol. Reprod. 63, 1192-1204. https://doi.org/10.1095/biolreprod63.4.1192
  41. Wang, H., Tranguch, S., Xie, H., Hanley, G., Das, S. K. and Dey, S. K. 2005. Variation in commercial rodent diets induces disparate molecular and physiological changes in the mouse uterus. Proc. Natl. Acad. Sci. USA. 102, 9960-9965. https://doi.org/10.1073/pnas.0501632102
  42. Wang, S., Yan, R., Wang, B., Du, P., Tan, W., Lammi, M. J. and Guo, X. 2018. Prediction of co-expression genes and integrative analysis of gene microarray and proteomics profile of Keshan disease. Sci. Rep. 8, 231. https://doi.org/10.1038/s41598-017-18599-x
  43. YAMADA, O., Todoroki, J. I., Takahashi, T. and Hashizume, K. 2002. The dynamic expression of extracellular matrix in the bovine endometrium at implantation. J. Vet. Med. Sci. 64, 207-214. https://doi.org/10.1292/jvms.64.207
  44. Yanagimachi, R. 1981. Mechanisms of fertilization in mammals. In Fertilization and embryonic development in vitro (pp. 81-182): Springer.
  45. Zenclussen, M. L., Casalis, P. A., Jensen, F., Woidacki, K. and Zenclussen, A. C. 2014. Hormonal fluctuations during the estrous cycle modulate heme oxygenase-1 expression in the uterus. Front. Endocrinol. (Lausanne) 5, 32. https://doi.org/10.3389/fendo.2014.00032
  46. Ziecik, A., Waclawik, A., Kaczmarek, M., Blitek, A., Jalali, B. M. and Andronowska, A. 2011. Mechanisms for the establishment of pregnancy in the pig. Reprod. Dom. Anim. 46, 31-41.