Effects of pentoxifylline on mouse oocytes maturation and qualityin vitro

Document Type : Original Article

Authors

Department of obstetrics-gynecology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, China

10.22038/ijbms.2024.77926.16856

Abstract

Objective(s): To investigate the impact of Pentoxifylline (PTX) on the in vitro maturation (IVM) of mouse oocytes and its effect on oocyte quality.
Materials and Methods: This experimental study involved culturing mouse oocytes in an IVM medium with varying PTX concentrations (0-100 μM). Post-culture, oocytes were assessed for nuclear and cytoplasmic maturation and quality indicators, including germinal vesicle breakdown (GVBD), first polar body extrusion (PB1E), cortical granules (CGs) distribution, spindle structure, chromosome alignment, and intracellular reactive oxygen species (ROS) levels.
Results: Treatment with PTX at 10, 25, and 50 μM concentrations significantly enhanced the nuclear maturation rates of oocytes. The optimal concentration was found to be 10 μM, as it resulted in the most favorable cytoplasmic maturation, characterized by improved distribution of CGs, spindle structure, and chromosome alignment. Additionally, treatment with 10 μM PTX effectively reduced reactive oxygen species (ROS) levels.
Conclusion: PTX supplementation at specific concentrations enhances mouse oocyte maturation and quality, potentially by facilitating CG distribution, spindle integrity, and chromosome alignment and by reducing ROS production.

Keywords

Main Subjects


1.    LR A. In vitro production of embryos in swine. Theriogenology 2002; 57:256-273.
2.    Child TJ, Phillips SJ, Abdul-Jalil AK, Gulekli B, Tan SL. A comparison of in vitro maturation and in vitro fertilization for women with polycystic ovaries. Obstet Gynecol 2002; 100:665-670.
3.    Eppig JJ, O’Brien MJ, Wigglesworth K, Nicholson A, Zhang W, King BA. Effect of in vitro maturation of mouse oocytes on the health and lifespan of adult offspring. Hum Reprod 2008; 24:922-928.
4.    Gosden R, Krapez J, Briggs D. Growth and development of the mammalian oocyte. Bioassays 1997; 19:875-882.
5.    Conti M, Franciosi F. Acquisition of oocyte competence to develop as an embryo: integrated nuclear and  cytoplasmic events. Hum Reprod Update 2018; 24:245-266.
6.    Eppig JJ, Schultz RM, O’Brien M, Chesnel F. Relationship between the developmental programs controlling nuclear and cytoplasmic maturation of mouse oocytes. Dev Biol 1994; 164:1-9.
7.    Salamone DF, Damiani P, Fissore RA, Robl JM, Duby RT. Biochemical and developmental evidence that ooplasmic maturation of prepubertal bovine oocytes is compromised. Biol Reprod 2001; 64:1761-1768.
8.    Roy PK, Qamar AY, Tanga BM, Fang X, Kim G, Bang S, et al. Enhancing oocyte competence with milrinone as a phosphodiesterase 3A inhibitor to improve the development of porcine cloned embryos. Front Cell Dev Biol 2021; 30:1-9.
9.    Nogueira D, Cortvrindt R, De Matos DG, Vanhoutte L, Smitz J. Effect of phosphodiesterase type 3 inhibitor on developmental competence of immature mouse oocytes in vitro1. Biol Reprod 2003; 69:2045-2052.
10.    Gupta A, Chaube SK. Cilostamide and rolipram prevent spontaneous meiotic resumption from diplotene arrest in rat oocytes cultured in vitro. Eur J Pharmacol 2020; 878:173115.
11.    Gupta A, Pandey AN, Sharma A, Tiwari M, Yadav PK, Yadav AK, et al. Cyclic nucleotide phosphodiesterase inhibitors: possible therapeutic drugs for female fertility regulation. Eur J Pharmacol 2020; 883:1-6.
12.    Donate-Correa J, Tagua VG, Ferri C, Martín-Núñez E, Hernández-Carballo C, Ureña-Torres P, et al. Pentoxifylline for renal protection in diabetic kidney disease. A model of old drugs for new horizons. J Clin Med 2019; 8:287-303.
13.    Shen MR, Chiang PH, Yang RC, Hong CY, Chen SS. Pentoxifylline stimulates human sperm motility both in vitro and after oral therapy. Brit J Clin Pharmaco1991; 31:711-714.
14.    Xian Y, Jiang M, Liu B, Zhao W, Zhou B, Liu X, et al. A cryoprotectant supplemented with pentoxifylline can improve the effect of freezing on the motility of human testicular sperm. Zygote 2021; 22:1-6.
15.    Dhulqarnain AO, Takzaree N, Hassanzadeh G, Tooli H, Malekzadeh M, Khanmohammadi N, et al. Pentoxifylline improves the survival of spermatogenic cells via oxidative stress suppression and upregulation of PI3K/AKT pathway in mouse model of testicular torsion-detorsion. Helion 2021; 7:1-11.
16.    Beygi Z, Forouhari S, Mahmoudi E, Hayat SMG, Nourimand F. Role of oxidative stress and antioxidant supplementation in male fertility. Curr Mol Med 2021; 21:265-282.
17.    S B. Cows are not mice: the role of cyclic AMP, phosphodiesterases, and adenosine monophosphate-activated protein kinase in the maintenance of meiotic arrest in bovine oocytes. Mol Reprod Dev 2011; 78:734-743.
18.    Mermillod P, Tomanek M, Marchal R, Meijer L. High developmental competence of cattle oocytes maintained at the germinal vesicle stage for 24 hr in culture by specific inhibition of MPF kinase activity. Mol Reprod Dev 2000; 55:89-95.
19.    Ramos Leal G, Santos Monteiro CA, Souza-Fabjan JMG, de Paula Vasconcelos CO, Garcia Nogueira LA, Reis Ferreira AM, et al. Role of cAMP modulator supplementations during oocyte in vitro maturation in domestic animals. Anim Reprod Sci 2018; 199:1-14.
20.    Conti M. Phosphodiesterases and regulation of female reproductive function. Curr Opin Pharmacol 2011; 11:665-669.
21.    Gupta A, Tiwari M, Prasad S, Chaube SK. Role of cyclic nucleotide phosphodiesterases during meiotic resumption from diplotene arrest in mammalian oocytes. J Cell Biochem 2017; 118:446-452.
22.    Kala M, Shaikh MV, Nivsarkar M. Equilibrium between anti‐oxidants and reactive oxygen species: a requisite for oocyte development and maturation. Reprod Med Biol 2017; 16:28-35.
23.    Dai X, Lu Y, Zhang M, Miao Y, Zhou C, Cui Z, et al. Melatonin improves the fertilization ability of post-ovulatory aged mouse oocytes by stabilizing ovastacin and juno to promote sperm binding and fusion. Hum Reprod 2017; 2017:1-30.
24.    Wang S, He G, Chen M, Zuo T, Xu W, Liu X. The role of antioxidant enzymes in the ovaries. Oxid Med Cell Longev 2017; 2017:1-14.
25.    Premkumar KV, Chaube SK. Increased level of reactive oxygen species persuades postovulatory aging-mediated spontaneous egg activation in rat eggs cultured in vitro. In Vitro Cell Dev Biol Anim 2016; 52:576-588.
26.    Satish M, Kumari S, Deeksha W, Abhishek S, Nitin K, Adiga SK, et al. Structure-based redesigning of pentoxifylline analogs against selective phosphodiesterases to modulate sperm functional competence for assisted reproductive technologies. Sci Rep 2021; 11:12293-12310.
27.    Ferrer-Vaquer A, Barragán M, Rodríguez A, Vassena R. Altered cytoplasmic maturation in rescued in vitro matured oocytes. Hum Reprod 2019; 34:1095-1105.
28.    Hoshino Y. Updating the markers for oocyte quality evaluation: intracellular temperature as a new index. Reprod Med Biol 2018; 17:434-441.
29.    Chaube SK. Effects of pentoxifylline and caffeine on spontaneous maturation of rat oosytes. Health and Population; Perspectives and Issues 2000; 23:177-189.
30.    Yougbare I, Belemnaba L, Morin C, Abusnina A, Senouvo YF, Keravis T, et al. NCS 613, a potent PDE4 inhibitor, displays anti-inflammatory and anti-proliferative properties on A549 lung epithelial cells and human lung adenocarcinoma explants. Front Pharmacol 2020; 11:1266-1275.
31.    Tsafriri A, Chun S, Zhang R, Hsueh AJW, Conti M. Oocyte maturation involves compartmentalization and opposing changes of cAMP levels in follicular somatic and germ cells: studies using selective phosphodiesterase inhibitors. Dev Biol 1996; 178:393-402.
32.    Park JE, Kim M, Lee J, Chai C, Lee ST, Lee E. in vitro maturation on an agarose matrix improves the developmental competence of porcine oocytes. Theriogenology 2020; 157:7-17.
33.    Lin T, Lee JE, Kang JW, Oqani RK, Cho ES, Kim SB, et al. Melatonin supplementation during prolonged in vitro maturation improves the quality and development of poor-quality porcine oocytes via anti-oxidative and anti-apoptotic effects. Mol Reprod Dev 2018; 85:665-681.
34.    Lin T, Lee JE, Oqani RK, Kim SY, Cho ES, Jeong YD, et al. Tauroursodeoxycholic acid improves pre-implantation development of porcine SCNT embryo by endoplasmic reticulum stress inhibition. Reprod  Biol 2016; 16:269-278.
35.    Jeseta M, Budna J, Kranc W, Hanulakova S, Bryja A, Chachuła A, et al. Expression of genes encoding zona pellucida glycoproteins and cortical granule distribution in porcine oocytes isolated from small and medium follicles in relation to puberty status of donors. Czech J Anim Sci 2017; 62:234-241.
36.    Vogt E, Tokuhiro K, Guo M, Dale R, Yang G, Shin S, et al. Anchoring cortical granules in the cortex ensures trafficking to the plasma membrane for post-fertilization exocytosis. Nat Commun 2019; 10:2271-2284.
37.    Coticchio G, Dal Canto M, Fadini R, Mignini Renzini M, Guglielmo MC, Miglietta S, et al. Ultrastructure of human oocytes after in vitro maturation. Mol Hum Reprod 2016; 22:110-118.
38.    Liu X, Mal S, Miao D, Liu D, Bao S, Tan J. Cortical granules behave differently in mouse oocytes matured under different conditions. Hum Reprod 2005; 20:3402-3413.
39.    Ma R, Zhang J, Liu X, Li L, Liu H, Rui R, et al. Involvement of Rab6a in organelle rearrangement and cytoskeletal organization during mouse oocyte maturation. Sci Rep 2016; 6:23560-23569.
40.    Hassold T, Hunt P. To err (meiotically) is human: the genesis of human aneuploidy. Nat Rev Genet 2001; 2:280-291.
41.    Cetica PD, Pintos LN, Dalvit GC, Beconi MT. Antioxidant enzyme activity and oxidative stress in bovine oocyte in vitro maturation. IUBMB Life 2001; 51:57-64.
42.    Hancock JT, Desikan R, Neill SJ. Role of reactive oxygen species in cell signalling pathways. Biochem Soc Trans 2001; 29:345-350.
43.    Di Emidio G, Falone S, Vitti M, D’Alessandro AM, Vento M, Di Pietro C, et al. SIRT1 signalling protects mouse oocytes against oxidative stress and is deregulated during aging. Hum Reprod 2014; 29:2006-2017.
44.    Jaffe LA, Egbert JR. Regulation of mammalian oocyte meiosis by intercellular communication within the ovarian follicle. Annu Rev Physiol 2017; 79:237-260.
45.    Zhang M, Su Y, Sugiura K, Xia G, Eppig JJ. Granulosa cell ligand NPPC and its receptor NPR2 maintain meiotic arrest in mouse oocytes. Science 2010; 330:366-369.