中山大学附属第六医院生殖医学中心,广东 广州 510655
周怡,硕士研究生,研究方向:生殖医学,E-mail: zhouy236@mail2.susy.edu.cn
收稿:2020-12-29,
纸质出版:2021-03-20
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周怡,李婷婷,郭映纯等.卵泡液中神经营养因子4及卵丘细胞TrkB受体与卵子发育潜能的关系[J].中山大学学报(医学科学版),2021,42(02):257-265.
ZHOU Yi,LI Ting-ting,GUO Ying-chun,et al.Relationship between Follicular-fluid Neurotrophin-4, TrkB Receptors in Cumulus Cells and Oocyte Developmental Competence[J].Journal of Sun Yat-sen University(Medical Sciences),2021,42(02):257-265.
周怡,李婷婷,郭映纯等.卵泡液中神经营养因子4及卵丘细胞TrkB受体与卵子发育潜能的关系[J].中山大学学报(医学科学版),2021,42(02):257-265. DOI:
ZHOU Yi,LI Ting-ting,GUO Ying-chun,et al.Relationship between Follicular-fluid Neurotrophin-4, TrkB Receptors in Cumulus Cells and Oocyte Developmental Competence[J].Journal of Sun Yat-sen University(Medical Sciences),2021,42(02):257-265. DOI:
目的
2
探索人卵泡液中神经营养因子4(NT-4)及卵丘颗粒细胞中TrkB受体的表达与卵子发育潜能的关系。
方法
2
收集2020年5月至2020年11月在中山大学附属第六医院生殖中心,因男方因素行卵胞浆内单精子注射(ICSI)治疗的63例患者的卵泡液和卵丘颗粒细胞,用ELISA检测卵泡液中NT-4水平,实时荧光定量PCR检测卵丘颗粒细胞中TrkB受体两种不同亚型TrkB-fl和TrkB-t1的表达水平,分析与卵子成熟、受精和胚胎发育的关系。
结果
2
卵泡液中NT-4水平与正常受精数(
r
s
=0.250,
P
=0.048)、可利用胚胎数(
r
s
=0.320,
P
=0.011)、优质胚胎数(
r
s
=0.327,
P
=0.009)和优质囊胚数(
r
s
=0.303,
P
=0.029)呈正相关。卵丘颗粒细胞中TrkB-t1在高囊胚形成率组(≥60%)和高优质囊胚率组(≥50%)中的表达均较低[0.86 (0.60, 1.85)
vs.
2.29 (1.09, 3.44) ,
P
=0.008; 0.84(0.64, 1.45)
vs.
1.73 (0.96, 3.14) ,
P
=0.031]。多重线性回归分析结果示优质胚胎数受获卵数(
P=
0.001)、卵泡液中NT-4水平(
P=
0.005)和卵丘颗粒细胞TrkB-t1表达水平(
P=
0.049)影响。
结论
2
人卵泡液中NT-4水平与ICSI患者卵子发育潜能正相关,其可能在卵子发育过程中发挥着重要作用。卵丘颗粒细胞中TrkB-t1的高表达与卵子发育潜能受损有关。
Objective
2
To investigate whether the neurotrophin-4 (NT-4) in human follicular fluid (FF) and the expression of tropomyosin-related kinase B (TrkB) receptors in cumulus cells (CCs) have any correlation with the developmental competence of oocytes.
Method
2
FF and CCs were collected from 63 patients undergoing intracytoplasmic sperm injection (ICSI) in the Reproductive Medicine Center from May to November 2020. NT-4 level in FF was measured by enzyme-linked immunosorbent assay (ELISA) method. The expression levels of two major TrkB isoforms, the full-length receptor (TrkB-fl) and the truncated receptor (TrkB-t1), were quantified in CCs by real-time PCR. The correlation of oocyte maturation, fertilization and embryo development with NT-4 level in FF, TrkB-fl and TrkB-t1 expression in CCs were analyzed.
Results
2
NT-4 level in human FF was positively correlated with the number of normally fertilized oocytes (
r
s
=0.250,
P
=0.048), available embryos (
r
s
=0.320,
P
=0.011), top-quality embryos (
r
s
=0.327,
P
=0.009) and top-quality blastocysts (
r
s
=0.303,
P
=0.029). The expression level of TrkB-t1 gene in CCs was negatively associated with a higher blastocyst formation rate (≥60%) and top-quality blastocyst rate (≥50%) [0.86 (0.60, 1.85)
vs.
2.29 (1.09, 3.44),
P
=0.008; 0.84 (0.64, 1.45)
vs.
1.73 (0.96, 3.14),
P
=0.031]. Multiple linear regression analysis showed that the number of top-quality embryos was affected by the number of oocytes retrieved (
P=
0.001), FF NT-4 level (
P=
0.005) and the expression of TrkB-t1 gene in CCs (
P=
0.049).
Conclusion
2
FF NT-4 level was positively associated with oocyte developmental competence, and it might play an important role in the development of oocytes. Over-expressed TrkB-t1 in CCs might be related to compromised oocyte developmental potential.
Gibon J , Barker PA . Neurotrophins and proneurotrophins: focus on synaptic activity and plasticity in the brain [J]. Neuroscientist , 2017 , 23 ( 6 ): 587 - 604 .
Chang HM , Wu HC , Sun ZG , et al . Neurotrophins and glial cell line-derived neurotrophic factor in the ovary: physiological and pathophysiological implications [J]. Hum Reprod Update , 2019 , 25 ( 2 ): 224 - 242 .
Streiter S , Fisch B , Sabbah B , et al . The importance of neuronal growth factors in the ovary [J]. Mol Hum Reprod , 2016 , 22 ( 1 ): 3 - 17 .
Childs AJ , Bayne RA , Murray AA , et al . Differential expression and regulation by activin of the neurotrophins BDNF and NT4 during human and mouse ovarian development [J]. Dev Dyn , 2010 , 239 ( 4 ): 1211 - 1219 .
Farhi J , Fisch B , Garor R , et al . Neurotrophin 4 enhances in vitro follicular assembly in human fetal ovaries [J]. Fertil Steril , 2011 , 95 ( 4 ): 1267 - 1271 .
Seifer DB , Feng B , Shelden RM , et al . Neurotrophin-4/5 and neurotrophin-3 are present within the human ovarian follicle but appear to have different paracrine/autocrine functions [J]. J Clin Endocrinol Metab , 2002 , 87 ( 10 ): 4569 - 4571 .
Kerr B , Garcia-Rudaz C , Dorfman M , et al . NTRK1 and NTRK2 receptors facilitate follicle assembly and early follicular development in the mouse ovary [J]. Reproduction , 2009 , 138 ( 1 ): 131 - 140 .
Dorfman MD , Kerr B , Garcia-Rudaz C , et al . Neurotrophins acting via TRKB receptors activate the JAGGED1-NOTCH2 cell-cell communication pathway to facilitate early ovarian development [J]. Endocrinology , 2011 , 152 ( 12 ): 5005 - 5016 .
Fenner BM . Truncated TrkB: Beyond a dominant negative receptor [J]. Cytokine Growth Factor Rev , 2012 , 23 ( 1-2 ): 15 - 24 .
Vanorny DA , Mayo KE . The role of Notch signaling in the mammalian ovary [J]. Reproduction , 2017 , 153 ( 6 ): 187 - 204 .
Harel S . Tyrosine kinase B receptor and its activated neurotrophins in ovaries from human fetuses and adults [J]. Mol Hum Reprod , 2006 , 12 ( 6 ): 357 - 365 .
Racowsky C , Combelles CM , Nureddin A , et al . Day 3 and day 5 morphological predictors of embryo viability [J]. Reprod Biomed Online , 2003 , 6 ( 3 ): 323 - 331 .
Gardner DK , Lane M , Stevens J , et al . Blastocyst score affects implantation and pregnancy outcome: towards a single blastocyst transfer [J]. Fertil Steril , 2000 , 73 ( 6 ): 1155 - 1158 .
Da Broi MG , Giorgi VSI , Wang F , et al . Influence of follicular fluid and cumulus cells on oocyte quality: clinical implications [J]. J Assist Reprod Gen , 2018 , 35 ( 5 ): 735 - 751 .
Zhai Y , Yao G , Rao F , et al . Excessive nerve growth factor impairs bidirectional communication between the oocyte and cumulus cells resulting in reduced oocyte competence [J]. Reprod Biol Endocrin , 2018 , 16 ( 1 ): 28 - 38 .
Wang X , Sun Z , Zhen J , et al . Brain-derived neurotrophic factor from follicular fluid is positively associated with rate of mature ooocytes collected and cleavage rate in intracytoplasmic sperm injection patients [J]. J Assist Reprod Gen , 2011 , 28 ( 11 ): 1053 - 1058 .
Buyuk E , Santoro N , Cohen HW , et al . Reduced neurotrophin receptor tropomyosin-related kinase A expression in human granulosa cells: a novel marker of diminishing ovarian reserve [J]. Fertil Steril , 2011 , 96 ( 2 ): 474 - 478 .
Chow R , Wessels JM , Foster WG . Brain-derived neurotrophic factor (BDNF) expression and function in the mammalian reproductive tract [J]. Hum Reprod Update , 2020 , 26 ( 4 ): 545 - 564 .
Zhao X , Du F , Liu X , et al . Brain-derived neurotrophic factor (BDNF) is expressed in buffalo (Bubalus bubalis) ovarian follicles and promotes oocyte maturation and early embryonic development [J]. Theriogenology , 2019 , 130 ( 5 ): 79 - 88 .
Gupta VK , You Y , Gupta VB , et al . TrkB receptor signalling: implications in neurodegenerative, psychiatric and proliferative disorders [J]. Int J Mol Sci , 2013 , 14 ( 5 ): 10122 - 10142 .
Cao T , Matyas JJ , Renn CL , et al . Function and mechanisms of truncated BDNF receptor TrkB.T1 in neuropathic pain [J]. Cells , 2020 , 9 ( 5 ): 1194 .
Dorfman MD , Garcia-Rudaz C , Alderman Z , et al . Loss of Ntrk2/Kiss1r signaling in oocytes causes premature ovarian failure [J]. Endocrinology , 2014 , 155 ( 8 ): 3098 - 3111 .
Anderson RA , Bayne RAL , Gardner J , et al . Brain-derived neurotrophic factor is a regulator of human oocyte maturation and early embryo development [J]. Fertil Steril , 2010 , 93 ( 5 ): 1394 - 1406 .
Danelon V , Montroull LE , Unsain N , et al . Calpain-dependent truncated form of TrkB-FL increases in neurodegenerative processes [J]. Mol Cell Neurosci , 2016 , 75 ( 9 ): 81 - 92 .
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