بررسی رابطه بین افزایش غلظت BPA و تاثیر آن بر روی تغییرات بیان ژنهای Notch1-3 و Caspase3/7 در سلول‌‌های کومولوس زنان نابارور با پاسخ ضعیف تخمدان
محورهای موضوعی : ژنتیکسمیه افتاب سواد 1 , زهرا نورمحمدی 2 , اشرف معینی 3 , مرتضی کریمی پور 4
1 - دانشجوی دکتری، گروه زیست‌شناسی، دانشکده علوم پایه، واحد علوم و تحقیقات، دانشگاه آزاد اسلامی، تهران، ایران.
2 - دانشیار، گروه زیست‌شناسی، دانشکده علوم پایه، واحد علوم و تحقیقات، دانشگاه آزاد اسلامی، تهران، ایران
3 - استاد، گروه غدد درون‌ریز و ناباروری زنان، مرکز تحقیقات پزشکی باروری، موسسه زیست پزشکی باروری رویان، تهران، ایران.
4 - استاد، گروه پزشکی مولکولی، مرکز تحقیقات بیوتکنولوژی، انستیتو پاستور ایران، تهران، ایران
کلید واژه: رشد تخمک, غلظت BPA, تولیدمثل, کیفیت جنین,
چکیده مقاله :
هدف: هدف این پژوهش بررسی رابطه بین غلظت BPA موجود در مایع فولیکولی و تاثیر آن بر روی تغییرات بیان ژنهایNotch1، Notch2، Notch3، Caspase-3 و Caspase-7 در سلول‌‌های کومولوس زنان نابارور با پاسخ تحریک ضعیف تخمدان (POR Response) به دنبال تحریک تخمدانی با پروتکل آنتاگونیست هورمون آزادکننده گنادوتروپین (GnRH) است.مواد و روش: این مطالعه مورد-شاهدی بر روی 80 بیمار زن POR با سن کم‌تر از 35 سال انجام شد که در روز پانکچر تخمدان دارای 9-4 تخمک بالغ بودند. بیماران در دو گروه دسته‌بندی شدند. گروه اول شامل 40 زن POR بودند که از ظروف پلاستیکی استفاده می‌‌کردند و گروه دوم شامل 40 زن POR بودندکه استفاده کم‌تری از ظروف پلاستیکی داشتند. تغییرات بیان ژن در سلول‌‌های کومولوس با استفاده ازReal time PCR ارزیابی شد.نتایج: میزان بیان ژنهایNotch1، Notch2 و Notch3 در گروه اولیه به طور معنی‌‌داری کم‌تر از گروه دوم بود (05/0 .(p< در مقابل، میزان بیان Caspase-3 و Caspase-7 در بیماران POR در گروه اول در مقایسه با گروه دوم بالاتر بود (05/0 .(p<از طرف دیگر، همبستگی آماری معنی‌‌داری (05/0 (p<بین سطح بیان ژنهایNotch1، Notch2، Notch3، Caspase-3 و Caspase-7 با کیفیت تخمک بین دو گروه وجود داشت. میزان غلظت BPA در مایعات فولیکولی گروه اول در مقایسه با گروه دوم بیشتر بود (05/0 .(p<نتیجه‌گیری: تغییرات بیان ژنهای مورد مطالعه در بیماران POR با افزایش غلظت BPA ارتباط مثبت معناداری دارد. افزایش غلظت BPAرا می‌‌توان به عنوان یک عامل موثر در کاهش تولیدمثل و کاهش رشد تخمک در نظر گرفت.
Introduction: The aim of this study was to investigate the relationship between BPA concentration and alterations of Notch1, Notch2, Notch3, Caspase-3 and Caspase-7 genes expression in the cumulus cells of infertile women with poor ovarian stimulation response (POR) following the antagonist protocol.Materials and Methods: In this case-control study performed on 80 POR patients under 35 years of age, with 4-9 oocyte in puncture date, patients were divided into two groups. The first group consisted of 40 POR women who used plastic containers and the second group consisted of 40 POR women who used less plastic containers. Changes in the expression of Notch and Caspase genes in cumulus cells were evaluated usingQ-PCR technique.Results: In the POR patients, the expression of Notch1-3 genes in the first group was significantly lower than the second group (p<0.05). In contrast, the expression of Caspase-3 and Caspase-7 genes in the first group was significantly higher than the second group (p<0.05).On the other hand, in both groups, was a statistically significant correlation (p<0.05) between the expression levels of Notch1-3, Caspase-3 and Caspase-7 genes and quality of Oocytes. Also, concentration of BPA in the follicular fluids of the first group was higher compared to the second group (p<0.05).Conclusion: Alterations in the expression of Notch and Caspase genes in POR patients are associated with increased BPA concentration. Also, Increasing of the BPA concentration can be considered as an effective factor on the reducing of reproduction and oocyte growth.
Xiaona H, Dan Ch, Yonghua He, Zhu W, Zhou W, Zhang J. Bisphenol-A and Female Infertility: A Possible Role of Gene-Environment Interactions. Int. J. Environ. Res. Public Health. 2015; 12: 11101-11116.
Ferraretti, A.-P. ESHRE working group on Poor Ovarian Response. Definition ESHRE consensus on the definition of ‘poor response’ to ovarian stimulation forin vitro fertilization: The Bologna criteria. Hum. Reprod. 2011; 26: 1616-1624.
Nishikawa M, Iwano H, Yanagisawa R, Koike N, Inoue H, Yokota H. Placental transfer of conjugated bisphenol A and subsequent reactivation in the rat fetus. Environ. Health Perspect. 2010; 118: 1196-1203.
Rochester JR. Bisphenol A and human health: A review of the literature. Reprod Toxicol. 2013; 42:132–155.
Dang VH, Choi KC, Jeung EB. Tetra bromo diphenyl ether (BDE 47) evokes estrogenicity and calbindin-D9k expression through an estrogen receptor-mediated pathway in the uterus of immature rats. Toxicol. Sci. 2007; 97: 504-511.
NOLI AS, Ferrari S, Ricci E, Reschini M, Cipriani S, Dallagiovanna CH, Parazzini F, Somigliana E. The role of diet in unexpected poor response to ovarian hyper-stimulation: a cross-sectional study. Bio Medicine Online. 2020; S1472-6483(20): 30382-5.
Ricci E, Noli S, Cipriani S. Maternal and Paternal Caffeine Intake and ART Outcomes in Couples Referring to an Italian Fertility Clinic: A Prospective Cohort. Nutrients. 2018; 10: 1116.
Ferraretti AP, Marca La A, Fauser BC, Nargund G, Gianaroli L. ESHRE consensus on the definition of ‘poor response’ to ovarian stimulation for in vitro fertilization: the Bologna criteria. HumReprod. 2011; 26(7): 1616-1624.
Nagels HE, Rishworth JR, Siristatidis CS, Kroon B. Androgens (dehydroepiandrosterone or testosterone) for women undergoing assisted reproduction. Cochrane Database Syst Rev. 2015; 26(11): CD009749.
Pandian Z, McTavish AR, Aucott L, Chen SN, Wang PH, Cianci A, Tsai HW, Wen ZH, Lin LT. Interventions for ‘poor responders’ to controlled ovarian hyper stimulation (COH) in in-vitro fertilisation (IVF). Cochrane Database Syst Rev. 2010; 20(1): CD004379.
Humaidan P, Alviggi C, Fischer R, Esteves SC. The novel POSEIDON stratification of ‘Low prognosis patients in Assisted Reproductive Technology’ and its proposed marker of successful outcome. F1000Research. 2016; 5:2911.
Patrizio P, Vaiarelli A, Setti L, Tobler KJ, Shoham G, Leon M, Shohamgh Z. How to define, diagnose and treat poor responders? Responses from a worldwide survey of IVF clinics. Reprod Biomed Online. 2015; 30(6): 581-592.
Vanorny DA, Mayo KE. The role of Notch signaling in the mammalian ovary. Reproduction. 2017; 153:187-R204.
Salehi E, Aflatoonian R, Moeini A, Yamini N, Asadi E, Khosravizadeh Z, Dehghan Tarzjani M, Naghibi harat J, Abolhassan F. Apoptotic biomarkers in cumulus cells in relation to embryo quality in polycystic ovary syndrome. Arch Gynecol Obstet. 2017; 296:1219-1227.
Yacobi K, Wojtowicz A, Tsafriri A, Gross A. Gonado-tropins enhance caspase-3 and-7 activity and apoptosis in the theca-interstitial cells of rat preovulatory follicles in culture. Endocrinology. 2004;145(4):1943-1951.
rentnall M, Rodriguez-Menocal L, De Guevara RL, Cepero E, Boise LH. Caspase-9, caspase-3 and caspase-7 have dis-tinct roles during intrinsic apoptosis. BMC Cell Biol. 2013; 14(1):32.
Yacobi K, Wojtowicz A, Tsafriri A, Gross A. Gonado-tropins enhance caspase-3 and-7 activity and apoptosis in the theca-interstitial cells of rat preovulatory follicles in culture. Endocrinology. 2004;145(4):1943-1951.
Salehi E, Aflatoonian R, Moeini A, Yamini N, Asadi E, Khosravizadeh Z, Dehghan Tarzjani M, Naghibi harat J, Abolhassan F. Apoptotic biomarkers in cumulus cells in relation to embryo quality in polycystic ovary syndrome. Arch Gynecol Obstet. 2017;296:1219-1227.
Aftabsavad S, Noormohammadi Z, Moini A, Karimipoor M. Effect of Bisphenol A on alterations of ICAM-1 and HLA-G genes Expression and DNA methylation profiles in Cumulus Cells of Infertile Women with Poor Response to Ovarian Stimulation. Scientific Reports. 2021; 11, Article number: 9595.
NOLI AS, Ferrari S, Ricci E, Reschini M, Cipriani S, Dallagiovanna CH, Parazzini F, Somigliana E. The role of diet in unexpected poor response to ovarian hyper-stimulation: a cross-sectional study. Bio Medicine Online. 2020; S1472-6483(20): 30382-5.
Garg A, Bantle JP, Henry RR, Coulston A, Griver KA, Raatz SK, Brinkley L, Chen I, Grundy SM, Huet BA, Reaven GM. Effects of varying carbohydrate content of diet in patients with non-insulin-dependent diabetes mellitus. JAMA. 1994; 271:1421-14285.
Mumm JS, Kopan R. Notch signaling: from the outside in. Developmental biology. 2000; 228(2):151-165.
Das M, Djahanbakhch O, Hacihanefioglu B, Saridogan E, Ikram M, Ghali L, Raveendran M, Storey A. Granulosa cell survival and proliferation are altered in polycystic ovary syndrome. J Clin Endocrinol Metab. 2008; 93(3): 881-7.
Kaneko T, Ohta N, Saito T, Hiroi M. Effects of controlled ovarian hyperstimulation on oocyte quality in terms of the incidence of apoptotic granulosa cells. Journal of assisted reproduction and genetics. 2000; 17(10):580-585.
Billig H, Furuta I, Hsueh A. Estrogens inhibit and androgens enhance ovarian granulosa cell apoptosis. Endocrinology. 1993; 133(5):2204-2212.
Al-Gubory KH, Fowler PA, Garrel C. The roles of cellular reactive oxygen species, oxidative stress and antioxidants in pregnancy outcomes. The international journal of biochemistry & cell biology. 2010; 42(10):1634-1650.
Gubory AL, Fowler KH, Garrel C, The roles of cellular reactive oxygen species, oxidative stress and antioxidants in pregnancy outcomes. The international journal of biochemistry & cell biology. 2010; 42(10): 1634-1650.
Yuting F, Yajie Ch, Wei L, Chen J, Li J, Goldsmith S, Silber Sh, Liang X. Apoptosis of mural granulosa cells is increased in women with diminished ovarian reserve. Reproductive Physiology and Disease. 2019; 36: 1225-1235.
Corn CM, Hauser-Kronberger C, Moser M, Tews G, Ebner TH. Predictive value of cumulus cell apoptosis with regard to blastocyst development of corresponding gametes. Fertility and sterility. 2005; 84(3): 627-633.
Bosco L, Ruvolo G, Chiarelli R, Agnello M, Roccheri MC. Apoptotic Analysis of Cumulus Cells for the Selection of Competent Oocytes to Be Fertilized by Intracytoplasmic Sperm Injection (ICSI). Journal of Cells. 2015; 1(1): 8-19.
_||_Xiaona H, Dan Ch, Yonghua He, Zhu W, Zhou W, Zhang J. Bisphenol-A and Female Infertility: A Possible Role of Gene-Environment Interactions. Int. J. Environ. Res. Public Health. 2015; 12: 11101-11116.
Ferraretti, A.-P. ESHRE working group on Poor Ovarian Response. Definition ESHRE consensus on the definition of ‘poor response’ to ovarian stimulation forin vitro fertilization: The Bologna criteria. Hum. Reprod. 2011; 26: 1616-1624.
Nishikawa M, Iwano H, Yanagisawa R, Koike N, Inoue H, Yokota H. Placental transfer of conjugated bisphenol A and subsequent reactivation in the rat fetus. Environ. Health Perspect. 2010; 118: 1196-1203.
Rochester JR. Bisphenol A and human health: A review of the literature. Reprod Toxicol. 2013; 42:132–155.
Dang VH, Choi KC, Jeung EB. Tetra bromo diphenyl ether (BDE 47) evokes estrogenicity and calbindin-D9k expression through an estrogen receptor-mediated pathway in the uterus of immature rats. Toxicol. Sci. 2007; 97: 504-511.
NOLI AS, Ferrari S, Ricci E, Reschini M, Cipriani S, Dallagiovanna CH, Parazzini F, Somigliana E. The role of diet in unexpected poor response to ovarian hyper-stimulation: a cross-sectional study. Bio Medicine Online. 2020; S1472-6483(20): 30382-5.
Ricci E, Noli S, Cipriani S. Maternal and Paternal Caffeine Intake and ART Outcomes in Couples Referring to an Italian Fertility Clinic: A Prospective Cohort. Nutrients. 2018; 10: 1116.
Ferraretti AP, Marca La A, Fauser BC, Nargund G, Gianaroli L. ESHRE consensus on the definition of ‘poor response’ to ovarian stimulation for in vitro fertilization: the Bologna criteria. HumReprod. 2011; 26(7): 1616-1624.
Nagels HE, Rishworth JR, Siristatidis CS, Kroon B. Androgens (dehydroepiandrosterone or testosterone) for women undergoing assisted reproduction. Cochrane Database Syst Rev. 2015; 26(11): CD009749.
Pandian Z, McTavish AR, Aucott L, Chen SN, Wang PH, Cianci A, Tsai HW, Wen ZH, Lin LT. Interventions for ‘poor responders’ to controlled ovarian hyper stimulation (COH) in in-vitro fertilisation (IVF). Cochrane Database Syst Rev. 2010; 20(1): CD004379.
Humaidan P, Alviggi C, Fischer R, Esteves SC. The novel POSEIDON stratification of ‘Low prognosis patients in Assisted Reproductive Technology’ and its proposed marker of successful outcome. F1000Research. 2016; 5:2911.
Patrizio P, Vaiarelli A, Setti L, Tobler KJ, Shoham G, Leon M, Shohamgh Z. How to define, diagnose and treat poor responders? Responses from a worldwide survey of IVF clinics. Reprod Biomed Online. 2015; 30(6): 581-592.
Vanorny DA, Mayo KE. The role of Notch signaling in the mammalian ovary. Reproduction. 2017; 153:187-R204.
Salehi E, Aflatoonian R, Moeini A, Yamini N, Asadi E, Khosravizadeh Z, Dehghan Tarzjani M, Naghibi harat J, Abolhassan F. Apoptotic biomarkers in cumulus cells in relation to embryo quality in polycystic ovary syndrome. Arch Gynecol Obstet. 2017; 296:1219-1227.
Yacobi K, Wojtowicz A, Tsafriri A, Gross A. Gonado-tropins enhance caspase-3 and-7 activity and apoptosis in the theca-interstitial cells of rat preovulatory follicles in culture. Endocrinology. 2004;145(4):1943-1951.
rentnall M, Rodriguez-Menocal L, De Guevara RL, Cepero E, Boise LH. Caspase-9, caspase-3 and caspase-7 have dis-tinct roles during intrinsic apoptosis. BMC Cell Biol. 2013; 14(1):32.
Yacobi K, Wojtowicz A, Tsafriri A, Gross A. Gonado-tropins enhance caspase-3 and-7 activity and apoptosis in the theca-interstitial cells of rat preovulatory follicles in culture. Endocrinology. 2004;145(4):1943-1951.
Salehi E, Aflatoonian R, Moeini A, Yamini N, Asadi E, Khosravizadeh Z, Dehghan Tarzjani M, Naghibi harat J, Abolhassan F. Apoptotic biomarkers in cumulus cells in relation to embryo quality in polycystic ovary syndrome. Arch Gynecol Obstet. 2017;296:1219-1227.
Aftabsavad S, Noormohammadi Z, Moini A, Karimipoor M. Effect of Bisphenol A on alterations of ICAM-1 and HLA-G genes Expression and DNA methylation profiles in Cumulus Cells of Infertile Women with Poor Response to Ovarian Stimulation. Scientific Reports. 2021; 11, Article number: 9595.
NOLI AS, Ferrari S, Ricci E, Reschini M, Cipriani S, Dallagiovanna CH, Parazzini F, Somigliana E. The role of diet in unexpected poor response to ovarian hyper-stimulation: a cross-sectional study. Bio Medicine Online. 2020; S1472-6483(20): 30382-5.
Garg A, Bantle JP, Henry RR, Coulston A, Griver KA, Raatz SK, Brinkley L, Chen I, Grundy SM, Huet BA, Reaven GM. Effects of varying carbohydrate content of diet in patients with non-insulin-dependent diabetes mellitus. JAMA. 1994; 271:1421-14285.
Mumm JS, Kopan R. Notch signaling: from the outside in. Developmental biology. 2000; 228(2):151-165.
Das M, Djahanbakhch O, Hacihanefioglu B, Saridogan E, Ikram M, Ghali L, Raveendran M, Storey A. Granulosa cell survival and proliferation are altered in polycystic ovary syndrome. J Clin Endocrinol Metab. 2008; 93(3): 881-7.
Kaneko T, Ohta N, Saito T, Hiroi M. Effects of controlled ovarian hyperstimulation on oocyte quality in terms of the incidence of apoptotic granulosa cells. Journal of assisted reproduction and genetics. 2000; 17(10):580-585.
Billig H, Furuta I, Hsueh A. Estrogens inhibit and androgens enhance ovarian granulosa cell apoptosis. Endocrinology. 1993; 133(5):2204-2212.
Al-Gubory KH, Fowler PA, Garrel C. The roles of cellular reactive oxygen species, oxidative stress and antioxidants in pregnancy outcomes. The international journal of biochemistry & cell biology. 2010; 42(10):1634-1650.
Gubory AL, Fowler KH, Garrel C, The roles of cellular reactive oxygen species, oxidative stress and antioxidants in pregnancy outcomes. The international journal of biochemistry & cell biology. 2010; 42(10): 1634-1650.
Yuting F, Yajie Ch, Wei L, Chen J, Li J, Goldsmith S, Silber Sh, Liang X. Apoptosis of mural granulosa cells is increased in women with diminished ovarian reserve. Reproductive Physiology and Disease. 2019; 36: 1225-1235.
Corn CM, Hauser-Kronberger C, Moser M, Tews G, Ebner TH. Predictive value of cumulus cell apoptosis with regard to blastocyst development of corresponding gametes. Fertility and sterility. 2005; 84(3): 627-633.
Bosco L, Ruvolo G, Chiarelli R, Agnello M, Roccheri MC. Apoptotic Analysis of Cumulus Cells for the Selection of Competent Oocytes to Be Fertilized by Intracytoplasmic Sperm Injection (ICSI). Journal of Cells. 2015; 1(1): 8-19.