Effect of lysophosphatidic Acid on the Vascular Endothelial Growth Factor Expression in Autotransplanted Mouse Ovaries Encapsulated in Sodium Alginate
Abstract
Objective: The aim of this study was to evaluate the effect of lysophosphatidic acid (LPA) supplementation during in vitro culture and transplantation of mouse ovaries on the follicular development and expression of vascular endothelial growth factor (VEGF) as an angiogenesis factor at the mRNA and protein levels.
Materials and methods: Three weeks old mice ovaries were cultured in the presence and absence of LPA for 24 hours, then they were capsulated in sodium alginate in the presence and absence of LPA as four experimental groups. After transplantation the vaginal smears were performed daily to evaluate the initiation of the estrous cycle. The morphology and follicular distribution were analyzed at the first and fourth estrous cycles using hematoxylin and eosin staining. Then in the groups that showed higher and lower follicular development the immunohistochemistry assay was conducted to identify VEGF protein expression, and the real time RT-PCR was done to analyze the expression of Vegf gene at the first estrus cycle.
Results: The large size follicles and also the corpus luteum were prominent in all transplanted groups at fourth estrus cycle in comparison with intact control groups. The statistically lowest percentage of small size follicles and the highest percentages of large size follicles were seen in LPA+/LPA- group (p<0.05). The expression ratio of Vegf to β-actin was significantly higher in this group in comparison with non-LPA treated and intact control groups (p <0.05).
Conclusion: LPA as an angiogenesis factor increases the follicular development in transplanted ovaries but it causes early discharge of ovarian reserve.
1. Kim S, Lee Y, Lee S, Kim T. Ovarian tissue cryopreservation and transplantation in patients with cancer. Obstet Gynecol Sci 2018; 61 (4): 431-42.
2. Donfack N, Alves K, Araujo V, Cordova A, Figueiredo J, Smitz J, et al. Expectations and limitations of ovarian tissue transplantation. Zygote 2017; 25 (4): 391-403.
3. Fisch B, Abir R. Female fertility preservation: past, present and future. Reproduction 2018; 156 (1): F11-F27.
4. Xie S, Zhang X, Chen W, Xie C, Chen W, Cheng P, Zhou Y, Chen B. Developmental status: impact of short-term ischemia on follicular survival of whole ovarian transplantation in a rabbit model. PloS one 2015; 10 (8): e0135049.
5. Liu J, Van der Elst J, Van den Broecke R, Dhont M. Early massive follicle loss and apoptosis in heterotopically grafted newborn mouse ovaries. Hum Reprod 2002; 17 (3): 605-11.
6. Israely T, Nevo N, Harmelin A, Neeman M, Tsafriri A. Reducing ischaemic damage in rodent ovarian xenografts transplanted into granulation tissue. Hum Reprod 2006; 21 (6): 1368-79.
7. Parsley WM, Perez-Meza D. Review of factors affecting the growth and survival of follicular grafts.
J Cutan Aesthet Surg 2010; 3 (2): 69.
8. Kolusari A, Okyay AG, Koçkaya EA. The effect of erythropoietin in preventing ischemia–reperfusion injury in ovarian tissue transplantation. Reprod Sci 2018; 25 (3): 406-13.
9. Amorim EMGD, Damous LL, Durando MCS, Saraiva MVA, Koike MK, Montero EFdS. N-acetylcysteine improves morphologic and functional aspects of ovarian grafts in rats. Acta Cir Bras 2014; 29: 22-7.
10. Kang BJ, Wang Y, Zhang L, Li SW. Basic Fibroblast Growth Factor Improved Angiogenesis of Vitrified Human Ovarian Tissues after in vitro Culture and Xenotransplantation. Cryo letters 2017; 38 (3): 194-201.
11. Cho I, Lee YJ, Lee HJ, Choi IY, Shin JK, Lee S, et al. Angiopoietin-1 and-2 and vascular endothelial growth factor expression in ovarian grafts after cryopreservation using two methods. Clin Exp Reprod Med 2018; 45 (3): 143-8.
12. Dolmans MM, Cacciottola L, Amorim CA, Manavella D. Translational research aiming to improve survival of ovarian tissue transplants using adipose tissue‐derived stem cells. Acta Obstet Gynecol Scand 2019; 98 (5): 665-71.
13. Zand-Vakili M, Golkar-Narenji A, Mozdziak PE, Eimani H. An in vitro study on oocyte and follicles of transplanted ovaries treated with vascular endothelial growth factor.
J Turk Ger Gynecol Assoc 2017; 18 (4): 167.
14. Labied S, Delforge Y, Munaut C, Blacher S, Colige A, Delcombel R, et al. Isoform 111 of vascular endothelial growth factor (VEGF111) improves angiogenesis of ovarian tissue xenotransplantation. Transplantation 2013; 95 (3): 426-33.
15. Demeestere I, Simon P, Emiliani S, Delbaere A, Englert Y. Orthotopic and heterotopic ovarian tissue transplantation. Hum Reprod Update 2009; 15 (6): 649-65.
16. Ye X. Lysophospholipid signaling in the function and pathology of the reproductive system. Hum Reprod Update 2008; 14 (5): 519-36.
17. Sheng X, Yung YC, Chen A, Chun J. Lysophosphatidic acid signalling in development. Development 2015; 142 (8): 1390-5.
18. Ye X, Ishii I, Kingsbury MA, Chun J. Lysophosphatidic acid as a novel cell survival/apoptotic factor. Biochim Biophys Acta 2002; 1585 (2-3): 108-13.
19. Wocławek-Potocka I, Rawinska P, Kowalczyk-Zieba I, Boruszewska D, Sinderewicz E, Wasniewski T, et al. Lysophosphatidic acid (LPA) signaling in human and ruminant reproductive tract. Mediators Inflamm 2014; 2014: 649702.
20. Sinderewicz E, Grycmacher K, Boruszewska D, Kowalczyk-Zieba I, Staszkiewicz J, Slezak T, et al. Expression of factors involved in apoptosis and cell survival is correlated with enzymes synthesizing lysophosphatidic acid and its receptors in granulosa cells originating from different types of bovine ovarian follicles. Reprod Biol Endocrinol 2017; 15 (1): 72.
21. Yung YC, Stoddard NC, Chun J. LPA receptor signaling: pharmacology, physiology, and pathophysiology. J Lipid Res 2014; 55 (7): 1192-214.
22. Boruszewska D, Sinderewicz E, Kowalczyk-Zieba I, Grycmacher K, Woclawek-Potocka I. The effect of lysophosphatidic acid during in vitro maturation of bovine cumulus–oocyte complexes: cumulus expansion, glucose metabolism and expression of genes involved in the ovulatory cascade, oocyte and blastocyst competence. Reprod Biol Endocrinol 2015; 13 (1): 44.
23. Hwang S-U, Kim K-J, Kim E, Yoon JD, Park KM, Jin M, et al. Lysophosphatidic acid increases in vitro maturation efficiency via uPA-uPAR signaling pathway in cumulus cells. Theriogenology 2018; 113: 197-207.
24. Zhang JY, Jiang Y, Lin T, Kang JW, Lee JE, Jin DI. Lysophosphatidic acid improves porcine oocyte maturation and embryo development in vitro. Mol Reprod Dev 2015; 82 (1): 66-77.
25. Sinderewicz E, Grycmacher K, Boruszewska D, Kowalczyk-Zieba I, Staszkiewicz-Chodor J, Lukaszuk K, et al. Expression of genes for enzymes synthesizing lysophosphatidic acid, its receptors and follicle developmental factors derived from the cumulus-oocyte complex is dependent on the ovarian follicle type in cows. Anim Reprod Sci 2018; 192: 242-50.
26. Choi JW, Herr DR, Noguchi K, Yung YC, Lee C-W, Mutoh T, et al. LPA receptors: subtypes and biological actions. Annu Rev Pharmacol Toxicol 2010; 50: 157-86.
27. Abedpour N, Salehnia M, Ghorbanmehr N. Effect of lysophosphatidic acid on the follicular development and the expression of lysophosphatidic acid receptor genes during in vitro culture of mouse ovary. Vet Res Forum 2018; 9(1):59-66
28. Chen Y, Ramakrishnan DP, Ren B. Regulation of angiogenesis by phospholipid lysophosphatidic acid. Front Biosci (Landmark Ed) 2013; 18: 852-61.
29. Teo ST, Yung YC, Herr DR, Chun J. Lysophosphatidic acid in vascular development and disease. IUBMB life 2009; 61 (8): 791-9.
30. Tanaka M, Okudaira S, Kishi Y, Ohkawa R, Iseki S, Ota M, et al. Autotaxin stabilizes blood vessels and is required for embryonic vasculature by producing lysophosphatidic acid. J. Biol. Chem 2006; 281 (35): 25822-30.
31. Van Meeteren LA, Ruurs P, Stortelers C, Bouwman P, van Rooijen MA, Pradere JP, et al. Autotaxin, a secreted lysophospholipase D, is essential for blood vessel formation during development. Mol Cell Biol 2006; 26 (13): 5015-22.
32. Yukiura H, Hama K, Nakanaga K, Tanaka M, Asaoka Y, Okudaira S, et al. Autotaxin regulates vascular development via multiple lysophosphatidic acid (LPA) receptors in zebrafish. J. Biol. Chem 2011; 286 (51): 43972-83.
33. Wasniewski T, Woclawek-Potocka I. Altered expression of lysophosphatidic acid receptors, in association with the synthesis of estrogens and androgens in type 1 endometrial cancer biology. Gynecol Endocrinol 2018; 34 (5): 422-7.
34. Rivera-Lopez CM, Tucker AL, Lynch KR. Lysophosphatidic acid (LPA) and angiogenesis. Angiogenesis 2008; 11 (3): 301-10.
35. Hisano Y, Hla T. Bioactive lysolipids in cancer and angiogenesis. Pharmacol Ther 2019; 193: 91-8.
36. Chen S-U, Chou C-H, Lee H, Ho C-H, Lin C-W, Yang Y-S. Lysophosphatidic acid up-regulates expression of interleukin-8 and-6 in granulosa-lutein cells through its receptors and nuclear factor-κB dependent pathways: implications for angiogenesis of corpus luteum and ovarian hyperstimulation syndrome. J Clin Endocrinol Metab 2008; 93 (3): 935-43.
37. Abedpour N, Salehnia M, Ghorbanmehr N. The Effects of Lysophosphatidic Acid on The Incidence of Cell Death in Cultured Vitrified and Non-Vitrified Mouse Ovarian Tissue: Separation of Necrosis and Apoptosis Border. Cell J 2018; 20 (3): 403-11.
38. Byers SL, Wiles MV, Dunn SL, Taft RA. Mouse
estrous cycle identification tool and images. PloS one 2012; 7 (4): e35538.
39. Wang H, Mooney S, Wen Y, Behr B, Polan ML. Follicle development in grafted mouse ovaries after cryopreservation and subcutaneous transplantation. Am J Obstet Gynecol 2002; 187 (2): 370-4.
40. Commin L, Buff S, Rosset E, Galet C, Allard A, Bruyere P, et al. Follicle development in cryopreserved bitch ovarian tissue grafted to immunodeficient mouse. Reprod Fertil Dev 2012; 24 (3): 461-71.
41. Lin C-I, Chen C-N, Huang M-T, Lee S-J, Lin C-H, Chang C-C, et al. Lysophosphatidic acid upregulates vascular endothelial growth factor-C and tube formation in human endothelial cells through LPA1/3, COX-2, and NF-κB activation-and EGFR transactivation-dependent mechanisms. Cell Signal 2008; 20 (10): 1804-14.
42. Park SY, Jeong KJ, Lee J, Yoon DS, Choi WS, Kim YK, et al. Hypoxia enhances LPA-induced HIF-1alpha and VEGF expression: their inhibition by resveratrol. Cancer Lett 2007; 258 (1): 63-9.
2. Donfack N, Alves K, Araujo V, Cordova A, Figueiredo J, Smitz J, et al. Expectations and limitations of ovarian tissue transplantation. Zygote 2017; 25 (4): 391-403.
3. Fisch B, Abir R. Female fertility preservation: past, present and future. Reproduction 2018; 156 (1): F11-F27.
4. Xie S, Zhang X, Chen W, Xie C, Chen W, Cheng P, Zhou Y, Chen B. Developmental status: impact of short-term ischemia on follicular survival of whole ovarian transplantation in a rabbit model. PloS one 2015; 10 (8): e0135049.
5. Liu J, Van der Elst J, Van den Broecke R, Dhont M. Early massive follicle loss and apoptosis in heterotopically grafted newborn mouse ovaries. Hum Reprod 2002; 17 (3): 605-11.
6. Israely T, Nevo N, Harmelin A, Neeman M, Tsafriri A. Reducing ischaemic damage in rodent ovarian xenografts transplanted into granulation tissue. Hum Reprod 2006; 21 (6): 1368-79.
7. Parsley WM, Perez-Meza D. Review of factors affecting the growth and survival of follicular grafts.
J Cutan Aesthet Surg 2010; 3 (2): 69.
8. Kolusari A, Okyay AG, Koçkaya EA. The effect of erythropoietin in preventing ischemia–reperfusion injury in ovarian tissue transplantation. Reprod Sci 2018; 25 (3): 406-13.
9. Amorim EMGD, Damous LL, Durando MCS, Saraiva MVA, Koike MK, Montero EFdS. N-acetylcysteine improves morphologic and functional aspects of ovarian grafts in rats. Acta Cir Bras 2014; 29: 22-7.
10. Kang BJ, Wang Y, Zhang L, Li SW. Basic Fibroblast Growth Factor Improved Angiogenesis of Vitrified Human Ovarian Tissues after in vitro Culture and Xenotransplantation. Cryo letters 2017; 38 (3): 194-201.
11. Cho I, Lee YJ, Lee HJ, Choi IY, Shin JK, Lee S, et al. Angiopoietin-1 and-2 and vascular endothelial growth factor expression in ovarian grafts after cryopreservation using two methods. Clin Exp Reprod Med 2018; 45 (3): 143-8.
12. Dolmans MM, Cacciottola L, Amorim CA, Manavella D. Translational research aiming to improve survival of ovarian tissue transplants using adipose tissue‐derived stem cells. Acta Obstet Gynecol Scand 2019; 98 (5): 665-71.
13. Zand-Vakili M, Golkar-Narenji A, Mozdziak PE, Eimani H. An in vitro study on oocyte and follicles of transplanted ovaries treated with vascular endothelial growth factor.
J Turk Ger Gynecol Assoc 2017; 18 (4): 167.
14. Labied S, Delforge Y, Munaut C, Blacher S, Colige A, Delcombel R, et al. Isoform 111 of vascular endothelial growth factor (VEGF111) improves angiogenesis of ovarian tissue xenotransplantation. Transplantation 2013; 95 (3): 426-33.
15. Demeestere I, Simon P, Emiliani S, Delbaere A, Englert Y. Orthotopic and heterotopic ovarian tissue transplantation. Hum Reprod Update 2009; 15 (6): 649-65.
16. Ye X. Lysophospholipid signaling in the function and pathology of the reproductive system. Hum Reprod Update 2008; 14 (5): 519-36.
17. Sheng X, Yung YC, Chen A, Chun J. Lysophosphatidic acid signalling in development. Development 2015; 142 (8): 1390-5.
18. Ye X, Ishii I, Kingsbury MA, Chun J. Lysophosphatidic acid as a novel cell survival/apoptotic factor. Biochim Biophys Acta 2002; 1585 (2-3): 108-13.
19. Wocławek-Potocka I, Rawinska P, Kowalczyk-Zieba I, Boruszewska D, Sinderewicz E, Wasniewski T, et al. Lysophosphatidic acid (LPA) signaling in human and ruminant reproductive tract. Mediators Inflamm 2014; 2014: 649702.
20. Sinderewicz E, Grycmacher K, Boruszewska D, Kowalczyk-Zieba I, Staszkiewicz J, Slezak T, et al. Expression of factors involved in apoptosis and cell survival is correlated with enzymes synthesizing lysophosphatidic acid and its receptors in granulosa cells originating from different types of bovine ovarian follicles. Reprod Biol Endocrinol 2017; 15 (1): 72.
21. Yung YC, Stoddard NC, Chun J. LPA receptor signaling: pharmacology, physiology, and pathophysiology. J Lipid Res 2014; 55 (7): 1192-214.
22. Boruszewska D, Sinderewicz E, Kowalczyk-Zieba I, Grycmacher K, Woclawek-Potocka I. The effect of lysophosphatidic acid during in vitro maturation of bovine cumulus–oocyte complexes: cumulus expansion, glucose metabolism and expression of genes involved in the ovulatory cascade, oocyte and blastocyst competence. Reprod Biol Endocrinol 2015; 13 (1): 44.
23. Hwang S-U, Kim K-J, Kim E, Yoon JD, Park KM, Jin M, et al. Lysophosphatidic acid increases in vitro maturation efficiency via uPA-uPAR signaling pathway in cumulus cells. Theriogenology 2018; 113: 197-207.
24. Zhang JY, Jiang Y, Lin T, Kang JW, Lee JE, Jin DI. Lysophosphatidic acid improves porcine oocyte maturation and embryo development in vitro. Mol Reprod Dev 2015; 82 (1): 66-77.
25. Sinderewicz E, Grycmacher K, Boruszewska D, Kowalczyk-Zieba I, Staszkiewicz-Chodor J, Lukaszuk K, et al. Expression of genes for enzymes synthesizing lysophosphatidic acid, its receptors and follicle developmental factors derived from the cumulus-oocyte complex is dependent on the ovarian follicle type in cows. Anim Reprod Sci 2018; 192: 242-50.
26. Choi JW, Herr DR, Noguchi K, Yung YC, Lee C-W, Mutoh T, et al. LPA receptors: subtypes and biological actions. Annu Rev Pharmacol Toxicol 2010; 50: 157-86.
27. Abedpour N, Salehnia M, Ghorbanmehr N. Effect of lysophosphatidic acid on the follicular development and the expression of lysophosphatidic acid receptor genes during in vitro culture of mouse ovary. Vet Res Forum 2018; 9(1):59-66
28. Chen Y, Ramakrishnan DP, Ren B. Regulation of angiogenesis by phospholipid lysophosphatidic acid. Front Biosci (Landmark Ed) 2013; 18: 852-61.
29. Teo ST, Yung YC, Herr DR, Chun J. Lysophosphatidic acid in vascular development and disease. IUBMB life 2009; 61 (8): 791-9.
30. Tanaka M, Okudaira S, Kishi Y, Ohkawa R, Iseki S, Ota M, et al. Autotaxin stabilizes blood vessels and is required for embryonic vasculature by producing lysophosphatidic acid. J. Biol. Chem 2006; 281 (35): 25822-30.
31. Van Meeteren LA, Ruurs P, Stortelers C, Bouwman P, van Rooijen MA, Pradere JP, et al. Autotaxin, a secreted lysophospholipase D, is essential for blood vessel formation during development. Mol Cell Biol 2006; 26 (13): 5015-22.
32. Yukiura H, Hama K, Nakanaga K, Tanaka M, Asaoka Y, Okudaira S, et al. Autotaxin regulates vascular development via multiple lysophosphatidic acid (LPA) receptors in zebrafish. J. Biol. Chem 2011; 286 (51): 43972-83.
33. Wasniewski T, Woclawek-Potocka I. Altered expression of lysophosphatidic acid receptors, in association with the synthesis of estrogens and androgens in type 1 endometrial cancer biology. Gynecol Endocrinol 2018; 34 (5): 422-7.
34. Rivera-Lopez CM, Tucker AL, Lynch KR. Lysophosphatidic acid (LPA) and angiogenesis. Angiogenesis 2008; 11 (3): 301-10.
35. Hisano Y, Hla T. Bioactive lysolipids in cancer and angiogenesis. Pharmacol Ther 2019; 193: 91-8.
36. Chen S-U, Chou C-H, Lee H, Ho C-H, Lin C-W, Yang Y-S. Lysophosphatidic acid up-regulates expression of interleukin-8 and-6 in granulosa-lutein cells through its receptors and nuclear factor-κB dependent pathways: implications for angiogenesis of corpus luteum and ovarian hyperstimulation syndrome. J Clin Endocrinol Metab 2008; 93 (3): 935-43.
37. Abedpour N, Salehnia M, Ghorbanmehr N. The Effects of Lysophosphatidic Acid on The Incidence of Cell Death in Cultured Vitrified and Non-Vitrified Mouse Ovarian Tissue: Separation of Necrosis and Apoptosis Border. Cell J 2018; 20 (3): 403-11.
38. Byers SL, Wiles MV, Dunn SL, Taft RA. Mouse
estrous cycle identification tool and images. PloS one 2012; 7 (4): e35538.
39. Wang H, Mooney S, Wen Y, Behr B, Polan ML. Follicle development in grafted mouse ovaries after cryopreservation and subcutaneous transplantation. Am J Obstet Gynecol 2002; 187 (2): 370-4.
40. Commin L, Buff S, Rosset E, Galet C, Allard A, Bruyere P, et al. Follicle development in cryopreserved bitch ovarian tissue grafted to immunodeficient mouse. Reprod Fertil Dev 2012; 24 (3): 461-71.
41. Lin C-I, Chen C-N, Huang M-T, Lee S-J, Lin C-H, Chang C-C, et al. Lysophosphatidic acid upregulates vascular endothelial growth factor-C and tube formation in human endothelial cells through LPA1/3, COX-2, and NF-κB activation-and EGFR transactivation-dependent mechanisms. Cell Signal 2008; 20 (10): 1804-14.
42. Park SY, Jeong KJ, Lee J, Yoon DS, Choi WS, Kim YK, et al. Hypoxia enhances LPA-induced HIF-1alpha and VEGF expression: their inhibition by resveratrol. Cancer Lett 2007; 258 (1): 63-9.
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| Issue | Vol 15, No 2 (June 2021) | |
| Section | Original Articles | |
| DOI | https://doi.org/10.18502/jfrh.v15i2.6449 | |
| Keywords | ||
| Angiogenesis Inducing Agents Autologous Transplantation Lysophosphatidic Acid Ovary Vascular Endothelial Growth Factors | ||
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How to Cite
1.
Dehghan M, Shahbazi S, Salehnia M. Effect of lysophosphatidic Acid on the Vascular Endothelial Growth Factor Expression in Autotransplanted Mouse Ovaries Encapsulated in Sodium Alginate. J Family Reprod Health. 2021;15(2):91-98.
