Activity of Matrix Metalloproteinase 2 and 9 in Follicular Fluid and Seminal Plasma and Its Relation to Embryo Quality and Fertilization Rate

Atabakhsh, Mojgan; Khodadadi, Iraj; Amiri, Iraj; Mahjub, Hossain; Tavilani, Haidar

Activity of Matrix Metalloproteinase 2 and 9 in Follicular Fluid and Seminal Plasma and Its Relation to Embryo Quality and Fertilization Rate

Authors

Mojgan Atabakhsh ¹

Iraj Khodadadi ¹

Iraj Amiri ²

Hossain Mahjub ³

Haidar Tavilani ⁴

¹ Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

² Endometrium and Endometriosis Research Center, Fatemieh Hospital, Hamadan University of Medical Sciences, Hamadan, Iran

³ Social Determinants of Health Research Center and Department of Epidemiology, School of Public Health, Hamadan University of Medical Sciences, Hamadan, Iran

⁴ Gene targeting Lab, John Curtin School of Medical Research, The Australian National University, Hamadan, Iran

Abstract

Background: The purpose of this study was to evaluate the activity of matrix metalloproteinase 2 (MMP-2) and 9 (MMP-9) in follicular fluid and seminal plasma and the correlation of their activities with parameters that are important in successful intracytoplasmic sperm injection (ICSI). Methods: Seventy-four infertile couples admitted to the Research Center for Endometrium and Endometriosis to carry out ICSI method were enrolled in this study. Follicular fluid was collected after retrieving the oocyte. In addition, semen samples were collected and seminal plasma was used for determination of MMP2 and MMP-9 activity. Gelatin zymography electrophoresis was applied to measure MMPs activities in follicular fluid and seminal plasma. Results: In follicular fluid, there was a positive correlation between MMP-2 activity with oocyte (r=0.27, p=0.021) or embryo quality (r=0.30, p=0.014), but no correlation was observed between MMP-2 activity and oocyte count or fertilization. Activity of MMP-9 showed positive correlation with oocyte morphology (r=0.29, p=0.014). In addition, MMP-2 activity of seminal plasma had positive correlation with sperm count (r=0.28, p=0.015), fertilization (r=0.28, p=0.02), and embryo quality (r=0.28, r=0.026). Conclusion: MMP2 and MMP9 activities in seminal plasma have a positive effect on sperm count and motility. MMP-2 and MMP-9 activity in follicular fluid and seminal plasma could be important factors in embryo quality in patients undergoing ICSI and may affect the outcome of ICSI.

Keywords

fertilization

Follicular fluid

Matrix metalloproteinase 2

Matrix Metalloproteinase 9

Semen

Curry TE Jr, Osteen KG. The matrix metalloproteinase system: changes, regulation, and impact throughout the ovarian and uterine reproductive cycle. Endocr Rev. 2003;24(4):428-65.

Fanjul-Fernández M, Folgueras AR, Cabrera S, López-Otín C. Matrix metalloproteinases: evolution, gene regulation and functional analysis in mouse models. Biochim Biophys Acta. 2010;1803(1):3-19.

Baumgart E, Lenk SV, Loening SA, Jung K. Quantitative differences in matrix metalloproteinase (MMP)-2, but not in MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1 or TIMP-2, in seminal plasma of normozoospermic and azoospermic patients. Hum Reprod. 2002;17(11):2919-23.

Ferrer M, Rodriguez H, Zara L, Yu Y, Xu W, Oko R. MMP2 and acrosin are major proteinases associated with the inner acrosomal membrane and may cooperate in sperm penetration of the zona pellucida during fertilization. Cell Tissue Res. 2012;349(3):881-95.

Chen H, Fok KL, Yu S, Jiang J, Chen Z, Gui Y, et al. CD147 is required for matrix metalloproteinases-2 production and germ cell migration during spermatogenesis. Mol Hum Reprod. 2011;17(7):405-14.

Smith MF, Ricke WA, Bakke LJ, Dow MP, Smith GW. Ovarian tissue remodeling: role of matrix metalloproteinases and their inhibitors. Mol Cell Endocrinol. 2002;191(1):45-56.

Goldman S, Shalev E. MMPS and TIMPS in ovarian physiology and pathophysiology. Front Biosci. 2004;1;9:2474-83.

Liu D, Zhu C. Regulation of ovarian function by the matrix metalloproteinase system. Chin Sci Bull. 2002;47(14):1145-9.

Hashemitabar M, Bahmanzadeh M, Mostafaie A, Orazizadeh M, Farimani M, Nikbakht R. A proteomic analysis of human follicular fluid: comparison between younger and older women with normal FSH levels. Int J Mol Sci. 2014;29;15(10):17518-40.

Magli MC, Jones GM, Lundin K, van den Abbeel E. Atlas of human embryology: from oocytes to preimplantation embryos. Preface. Hum Reprod. 2012;27 Suppl 1:i1.

WHO. WHO laboratory manual for the examination and processing of human semen. 5th ed. Geneva, CH: World Health Organization. 2010. 287 p.

Kruger NJ. The Bradford method for protein quantitation. In: Walker JM, editor. Basic protein and peptide protocols. Totowa, NJ: Humana Press; 1994. p. 9-15.

Ranjbaran JF, Farimani M, Tavilani H, Ghorbani M, Karimi JF, Poormonsefi F, et al. Matrix metalloproteinases 2 and 9 and MMP9/NGAL complex activity in women with PCOS. Reproduction. 2016;151(4):305-11.

Buchman-Shaked O, Kraiem Z, Gonen Y, Goldman S. Presence of matrix metalloproteinases and tissue inhibitor of matrix metalloproteinase in human sperm. J Androl. 2002;23(5):702-8.

Wiener-Megnazi Z, Vardi L, Lissak A, Shnizer S, Zeev Reznick A, Ishai D, et al. Oxidative stress indices in follicular fluid as measured by the thermochemiluminescence assay correlate with outcome parameters in in vitro fertilization. Fertil Steril. 2004;82 Suppl 3:1171-6.

Gottsch ML, Van Kirk EA, Murdoch WJ. Role of matrix metalloproteinase 2 in the ovulatory folliculo-luteal transition of ewes. Reproduction. 2002;124(3):347-52.

Rienzi L, Balaban B, Ebner T, Mandelbaum J. The oocyte. Hum Reprod. 2012;27 Suppl 1:i2-21.

D'Ascenzo S, Giusti I, Millimaggi D, Marci R, Tatone C, Cardigno Colonna R, et al. Intrafollicular expression of matrix metalloproteinases and their inhibitors in normally ovulating women compared with patients undergoing in vitro fertilization treatment. Eur J Endocrinol. 2004;151(1):87-91.

Horka P, Malickova K, Jarosova R, Janatkova I, Zima T, Kalousova M. Matrix metalloproteinases in serum and the follicular fluid of women treated by in vitro fertilization. J Assist Reprod Genet. 2012;29(11):1207-12.

Baka S, Zourla K, Malamitsi-Puchner A, Makrakis E, Kaparos G, Demeridou S, et al. Intrafollicular levels of matrix metalloproteinases-2 and -9 in patients with polycystic ovaries are not associated with pregnancy rate during IVF cycle. In Vivo. 2009;23(1):89-92.

Prados FJ, Debrock S, Lemmen JG, Agerholm I. The cleavage stage embryo. Hum Reprod. 2012;27 Suppl 1:i50-71.

Lee DM, Lee TK, Song HB, Kim CH. The expression of matrix metalloproteinase-9 in human follicular fluid is associated with in vitro fertilisation pregnancy. BJOG. 2005;112(7):946-51.

Miller JE, Smith TT. The effect of intracytoplasmic sperm injection and semen parameters on blastocyst development in vitro. Hum Reprod. 2001;16(5):918-24.