Follicular Fluid from Infertile Women with Mild Endometriosis Impairs In Vitro Bovine Embryo Development: Potential Role of Oxidative Stress

Vanessa Silvestre Innocenti Giorgi; Rui Alberto Ferriani; Paula Andrea Navarro

doi:10.1055/s-0040-1718443

Revista Brasileira de Ginecologia e Obstetrícia / RBGO Gynecology and Obstetrics, Table of Contents

CC BY 4.0 · Rev Bras Ginecol Obstet 2021; 43(02): 119-125
DOI: 10.1055/s-0040-1718443

Original Article

Basic and translational Science/Endometriosis

Follicular Fluid from Infertile Women with Mild Endometriosis Impairs In Vitro Bovine Embryo Development: Potential Role of Oxidative Stress

Fluido folicular de mulheres inférteis com endometriose leve prejudica o desenvolvimento in vitro de embriões bovinos: Potencial papel do estresse oxidativo

Vanessa Silvestre Innocenti Giorgi

¹Human Reproduction Division, Department of Gynecology and Obstetrics, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil

,

Rui Alberto Ferriani

¹Human Reproduction Division, Department of Gynecology and Obstetrics, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil

²Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brasília, DF, Brazil

,

Paula Andrea Navarro

¹Human Reproduction Division, Department of Gynecology and Obstetrics, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil

²Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brasília, DF, Brazil

› Author Affiliations

Abstract

Objective To investigate whether follicular fluid (FF) from infertile women with mild endometriosis (ME) alters in vitro bovine embryo development, and whether the antioxidants N-acetyl-cysteine (NAC) and/or L-carnitine (LC) could prevent such damages.

Methods Follicular fluid was obtained from infertile women (11 with ME and 11 control). Bovine oocytes were matured in vitro divided in: No-FF, with 1% of FF from control women (CFF) or ME women (MEFF); with 1.5 mM NAC (CFF + NAC, MEFF + NAC), with 0.6 mg/mL LC (CFF + LC, MEFF + LC), or both antioxidants (CFF + NAC + LC, MEFF + NAC + LC). After in vitro fertilization, in vitro embryo culture was performed for 9 days.

Results A total of 883 presumptive zygotes were cultured in vitro. No differences were observed in cleavage rate (p = 0.5376) and blastocyst formation rate (p = 0.4249). However, the MEFF group (12.5%) had lower hatching rate than the No-FF (42.1%, p = 0.029) and CFF (42.9%, p = 0.036) groups. Addition of antioxidants in the group with CFF did not alter hatching rate (p ≥ 0.56), and in groups with MEFF, just NAC increased the hatching rate [(MEFF: 12.5% versus MEFF + NAC: 44.4% (p = 0.02); vs MEFF + LC: 18.8% (p = 0.79); versus MEFF + NAC + LC: 30.8% (p = 0.22)].

Conclusion Therefore, FF from infertile women with ME added to medium of in vitro maturation of bovine oocytes impairs hatching rate, and NAC prevented these damages, suggesting involvement of oxidative stress in worst of oocyte and embryo quality of women with ME.

Resumo

Objetivo Investigar se o fluido folicular (FF) de mulheres inférteis com endometriose leve (ME, na sigla em inglês) altera o desenvolvimento in vitro de embriões bovinos, e se os antioxidantes N-acetil-cisteína (NAC) e/ou L-carnitina (LC) poderiam prevenir possíveis danos.

Métodos O FF foi obtido de mulheres inférteis (11 com ME e 11 controles). Oócitos bovinos foram maturados in vitro divididos em: sem FF (No-FF), com 1% de FF de mulheres controle (CFF) ou mulheres com ME (MEFF); com 1,5 mM de NAC (CFF + NAC, MEFF + NAC), com 0,6 mg/mL de LC (CFF + LC, MEFF + LC), ou ambos antioxidantes (CFF + NAC + LC, MEFF + NAC + LC). Depois da fertilização in vitro, o cultivo in vitro de embriões foi realizado por 9 dias.

Resultados Um total de 883 zigotos presumidos foram cultivados in vitro. Nenhuma diferença foi observada na taxa de clivagem (p = 0,5376) e na taxa de formação de blastocistos (p = 0,4249). Entretanto, o grupo MEFF (12.5%) teve menor taxa de eclosão de blastocistos do que os grupos No-FF (42,1%, p = 0,029) e CFF (42,9%, p = 0,036). Adição de antioxidantes no grupo com CFF não alterou a taxa de eclosão (p ≥ 0.56), e nos grupos com MEFF, somente a NAC aumentou a taxa de eclosão [(MEFF: 12.5% versus MEFF + NAC: 44.4% (p = 0.02); versus MEFF + LC: 18.8% (p = 0.79); versus MEFF + NAC + LC: 30.8% (p = 0.22)].

Conclusão Portanto, o FF de mulheres inférteis com ME adicionado ao meio de maturação in vitro de oócitos bovinos prejudica a taxa de closão embrionária, e a NAC preveniu esses danos, sugerindo o envolvimento do estresse oxidativo na piora da qualidade oocitária e embrionária de mulheres com ME.

Keywords

infertility - endometriosis - oocyte quality - N-acetyl-cysteine - L-carnitine

Palavras-chave

infertilidade - endometriose - qualidade oocitária - N-acetil-cisteína - L-carnitina

Full Text

References

References
1 Burney RO, Giudice LC. Pathogenesis and pathophysiology of endometriosis. Fertil Steril 2012; 98 (03) 511-519
2 Augoulea A, Alexandrou A, Creatsa M, Vrachnis N, Lambrinoudaki I. Pathogenesis of endometriosis: the role of genetics, inflammation and oxidative stress. Arch Gynecol Obstet 2012; 286 (01) 99-103
3 Bulletti C, Coccia ME, Battistoni S, Borini A. Endometriosis and infertility. J Assist Reprod Genet 2010; 27 (08) 441-447
4 Revised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil Steril 1997; 67 (05) 817-821
5 Barbosa MA, Teixeira DM, Navarro PAAS, Ferriani RA, Nastri CO, Martins WP. Impact of endometriosis and its staging on assisted reproduction outcome: systematic review and meta-analysis. Ultrasound Obstet Gynecol 2014; 44 (03) 261-278
6 Hamdan M, Omar SZ, Dunselman G, Cheong Y. Influence of endometriosis on assisted reproductive technology outcomes: a systematic review and meta-analysis. Obstet Gynecol 2015; 125 (01) 79-88
7 Rossi AC, Prefumo F. The effects of surgery for endometriosis on pregnancy outcomes following in vitro fertilization and embryo transfer: a systematic review and meta-analysis. Arch Gynecol Obstet 2016; 294 (03) 647-655
8 Bérubé S, Marcoux S, Langevin M, Maheux R. The Canadian Collaborative Group on Endometriosis. Fecundity of infertile women with minimal or mild endometriosis and women with unexplained infertility. Fertil Steril 1998; 69 (06) 1034-1041
9 Akande VA, Hunt LP, Cahill DJ, Jenkins JM. Differences in time to natural conception between women with unexplained infertility and infertile women with minor endometriosis. Hum Reprod 2004; 19 (01) 96-103
10 Donnez J, Binda MM, Donnez O, Dolmans MM. Oxidative stress in the pelvic cavity and its role in the pathogenesis of endometriosis. Fertil Steril 2016; 106 (05) 1011-1017
11 Samimi M, Pourhanifeh MH, Mehdizadehkashi A, Eftekhar T, Asemi Z. The role of inflammation, oxidative stress, angiogenesis, and apoptosis in the pathophysiology of endometriosis: Basic science and new insights based on gene expression. J Cell Physiol 2019; 234 (11) 19384-19392
12 Da Broi MG, Navarro PA. Oxidative stress and oocyte quality: ethiopathogenic mechanisms of minimal/mild endometriosis-related infertility. Cell Tissue Res 2016; 364 (01) 1-7
13 Da Broi MG, Jordão Jr AA, Ferriani RA, Navarro PA. Oocyte oxidative DNA damage may be involved in minimal/mild endometriosis-related infertility. Mol Reprod Dev 2018; 85 (02) 128-136
14 Da Broi MG, Malvezzi H, Paz CC, Ferriani RA, Navarro PA. Follicular fluid from infertile women with mild endometriosis may compromise the meiotic spindles of bovine metaphase II oocytes. Hum Reprod 2014; 29 (02) 315-323
15 Giorgi VS, Da Broi MG, Paz CC, Ferriani RA, Navarro PA. N-acetyl-cysteine and l–carnitine prevent meiotic oocyte damage induced by follicular fluid from infertile women with mild endometriosis. Reprod Sci 2016; 23 (03) 342-351
16 Romero S, Pella R, Zorrilla I, Berrío P, Escudero F, Pérez Y. et al. Coenzyme Q10 improves the in vitro maturation of oocytes exposed to the intrafollicular environment of patients on fertility treatment. JBRA Assist Reprod 2020; 24 (03) 283-288
17 Adona PR, Lima Verde Leal C. Meiotic inhibition with different cyclin-dependent kinase inhibitors in bovine oocytes and its effects on maturation and embryo development. Zygote 2004; 12 (03) 197-204
18 Mansour G, Abdelrazik H, Sharma RK, Radwan E, Falcone T, Agarwal A. L-carnitine supplementation reduces oocyte cytoskeleton damage and embryo apoptosis induced by incubation in peritoneal fluid from patients with endometriosis. Fertil Steril 2009; 91 (5, Suppl) 2079-2086
19 Yazaki T, Hiradate Y, Hoshino Y, Tanemura K, Sato E. L-carnitine improves hydrogen peroxide-induced impairment of nuclear maturation in porcine oocytes. Anim Sci J 2013; 84 (05) 395-402
20 Bremer J, Woldegiorgis G, Schalinske K, Shrago E. Carnitine palmitoyltransferase. Activation by palmitoyl-CoA and inactivation by malonyl-CoA. Biochim Biophys Acta 1985; 833 (01) 9-16
21 Samuni Y, Goldstein S, Dean OM, Berk M. The chemistry and biological activities of N-acetylcysteine. Biochim Biophys Acta 2013; 1830 (08) 4117-4129
22 Dekhuijzen PN. Antioxidant properties of N-acetylcysteine: their relevance in relation to chronic obstructive pulmonary disease. Eur Respir J 2004; 23 (04) 629-636
23 Whitaker BD, Casey SJ, Taupier R. The effects of N-acetyl-L-cysteine supplementation on in vitro porcine oocyte maturation and subsequent fertilisation and embryonic development. Reprod Fertil Dev 2012; 24 (08) 1048-1054
24 de Loos F, van Vliet C, van Maurik P, Kruip TA. Morphology of immature bovine oocytes. Gamete Res 1989; 24 (02) 197-204
25 Ferreira EM, Vireque AA, Adona PR, Ferriani RA, Navarro PA. Prematuration of bovine oocytes with butyrolactone I reversibly arrests meiosis without increasing meiotic abnormalities after in vitro maturation. Eur J Obstet Gynecol Reprod Biol 2009; 145 (01) 76-80
26 Parrish JJ, Susko-Parrish JL, Leibfried-Rutledge ML, Critser ES, Eyestone WH, First NL. Bovine in vitro fertilization with frozen-thawed semen. Theriogenology 1986; 25 (04) 591-600
27 Parrish JJ, Susko-Parrish J, Winer MA, First NL. Capacitation of bovine sperm by heparin. Biol Reprod 1988; 38 (05) 1171-1180
28 Barcelos ID, Vieira RC, Ferreira EM, Martins WP, Ferriani RA, Navarro PA. Comparative analysis of the spindle and chromosome configurations of in vitro-matured oocytes from patients with endometriosis and from control subjects: a pilot study. Fertil Steril 2009; 92 (05) 1749-1752
29 Kawamura K, Chen Y, Shu Y, Cheng Y, Qiao J, Behr B. et al. Promotion of human early embryonic development and blastocyst outgrowth in vitro using autocrine/paracrine growth factors. PLoS One 2012; 7 (11) e49328
30 Tabibnejad N, Soleimani M, Aflatoonian A. Zona pellucida birefringence and meiotic spindle visualization are not related to the time-lapse detected embryo morphokinetics in women with polycystic ovarian syndrome. Eur J Obstet Gynecol Reprod Biol 2018; 230: 96-102
31 Sanchez AM, Pagliardini L, Cermisoni GC, Privitera L, Makieva S, Alteri A. et al. Does endometriosis influence the embryo quality and/or development? Insights from a large retrospective matched cohort study. Diagnostics (Basel) 2020; 10 (02) 83
32 Xu B, Guo N, Zhang XM, Shi W, Tong XH, Iqbal F, Liu YS. Oocyte quality is decreased in women with minimal or mild endometriosis. Sci Rep 2015; 5: 10779
33 Piromlertamorn W, Saeng-anan U, Vutyavanich T. Effects of ovarian endometriotic fluid exposure on fertilization rate of mouse oocytes and subsequent embryo development. Reprod Biol Endocrinol 2013; 11: 4
34 Nada AM, El-Noury A, Al-Inany H, Bibars M, Taha T, Salama S. et al. Effect of laser-assisted zona thinning, during assisted reproduction, on pregnancy outcome in women with endometriosis: randomized controlled trial. Arch Gynecol Obstet 2018; 297 (02) 521-528
35 Radzinsky VY, Orazov MR, Ivanov II, Khamoshina MB, Kostin IN, Kavteladze EV, Shustova VB. Implantation failures in women with infertility associated endometriosis. Gynecol Endocrinol 2019; 35 (sup1, Suppl 1) 27-30
36 Kirkegaard K, Hindkjaer JJ, Ingerslev HJ. Effect of oxygen concentration on human embryo development evaluated by time-lapse monitoring. Fertil Steril 2013; 99 (03) 738-744.e4
37 Goud PT, Goud AP, Joshi N, Puscheck E, Diamond MP, Abu-Soud HM. Dynamics of nitric oxide, altered follicular microenvironment, and oocyte quality in women with endometriosis. Fertil Steril 2014; 102 (01) 151-159.e5
38 Bromfield EG, Aitken RJ, Anderson AL, McLaughlin EA, Nixon B. The impact of oxidative stress on chaperone-mediated human sperm-egg interaction. Hum Reprod 2015; 30 (11) 2597-2613
39 Takeo T, Horikoshi Y, Nakao S, Sakoh K, Ishizuka Y, Tsutsumi A. et al. Cysteine analogs with a free thiol group promote fertilization by reducing disulfide bonds in the zona pellucida of mice. Biol Reprod 2015; 92 (04) 90
40 Harada M, Kishimoto K, Hagiwara R, Nakashima Y, Kurisu K, Kawaguchi Y. Infertility observed in female rats treated with N-acetyl-L-cysteine: Histopathological examination of ovarian follicles and recovery of fertility. Congenit Anom (Kyoto) 2003; 43 (03) 168-176