Role of growth factors of the TGFbeta superfamily in aberrant follicle development in polycystic ovary syndrome
TGFbeta超家族生长因子在多囊卵巢综合征卵泡发育异常中的作用
基本信息
- 批准号:MR/M012638/1
- 负责人:
- 金额:$ 51.18万
- 依托单位:
- 依托单位国家:英国
- 项目类别:Research Grant
- 财政年份:2015
- 资助国家:英国
- 起止时间:2015 至 无数据
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Polycystic Ovary Syndrome (PCOS) affects more than 5% of women of reproductive age and has a major impact both on fertility and on long-term health. It results in irregular menstruation, is the main reason for ovulation-related infertility and, because of its associated metabolic abnormalities, carries a high risk of developing diabetes. However we still know very little about its cause or causes, which makes diagnosis imprecise and means that we are treating the resulting symptoms rather than the underlying causes. The main problem that we are attempting to address in this application is to understand the reasons why women with PCOS ovulate infrequently or not at all. A woman is born with a supply of eggs that must last throughout her reproductive lifespan. These eggs are surrounded by a single layer of supporting (granulosa) cells and stored in tiny follicles in the ovary. This resting pool of follicles is termed the primordial pool. The processes that prompt primordial follicles to start growing remain unclear but there is evidence that locally produced growth factors play an important part, particularly those of the so-called transforming growth factor beta (TGFbeta) family. Much of this evidence comes from studies of mouse follicle development in our own laboratory. TGFbeta growth factors are proteins that are produced by and act in follicles of all sizes, including the very smallest, primordial, follicles. In our earlier studies of ovarian samples from women with PCOS, we have shown that the problems that lead to infrequent ovulation may lie in the very earliest stages of the life of the ovarian follicle and we have already shown that at least one of the TGFbeta family members (anti-Müllerian Hormone or AMH) is produced abnormally in very small follicles of women with PCOS. For the current proposal we will have unique access to ovarian tissue from women with and without PCOS, much of which will come from a research-orientated programme for conservation of ovary tissue in young women about to undergo treatment for cancer. Every sample that we obtain will be "spare" tissue samples that would normally be discarded. We will also be able to collect small biopsies of women with and without PCOS who are undergoing routine laparoscopy (to visualise the ovaries and Fallopian tubes) or who are having ovarian "drilling" as a procedure to stimulate ovulation.We will determine where and when (according to developmental stage) TGFbeta growth factors (and their receptor targets) are produced, how they signal within ovarian cells, how they may interact other growth factor networks, and whether these processes differ between normal and polycystic ovaries. We will also examine the effects of added TGFbeta growth factors in small samples of cultured ovarian tissue. We expect these studies will provide important clues not only to understanding fertility problems in women with PCOS but also how they may relate to the development of metabolic disorders, including diabetes, to which these women are predisposed.
多囊卵巢综合征(PCOS)影响超过5%的育龄妇女,对生育能力和长期健康都有重大影响。它导致月经不调,是排卵相关不孕症的主要原因,并且由于其相关的代谢异常,具有患糖尿病的高风险。然而,我们仍然对它的原因知之甚少,这使得诊断不准确,这意味着我们正在治疗由此产生的症状,而不是根本原因。我们在本申请中试图解决的主要问题是了解PCOS妇女排卵不频繁或根本不排卵的原因。一个女人出生时就有足够的卵子,这些卵子必须持续到她的整个生殖寿命。这些卵子被单层支持(颗粒)细胞包围,并储存在卵巢的微小卵泡中。这个卵泡的静止池被称为原始池。促使原始卵泡开始生长的过程尚不清楚,但有证据表明,局部产生的生长因子发挥了重要作用,特别是所谓的转化生长因子β(TGF β)家族。这些证据大部分来自我们自己实验室对小鼠卵泡发育的研究。TGF β生长因子是由所有大小的卵泡产生并在其中起作用的蛋白质,包括最小的原始卵泡。在我们早期对PCOS女性卵巢样本的研究中,我们已经表明导致排卵不频繁的问题可能存在于卵泡生命的最早阶段,我们已经表明至少有一种TGF β家族成员(抗苗勒管激素或AMH)在PCOS女性的非常小的卵泡中异常产生。对于目前的提案,我们将有独特的机会从患有和没有PCOS的女性获得卵巢组织,其中大部分将来自一个以研究为导向的计划,用于保护即将接受癌症治疗的年轻女性的卵巢组织。我们获得的每个样本都是通常会被丢弃的“备用”组织样本。我们也可以收集常规腹腔镜检查的PCOS患者和非PCOS患者的小活检标本(以可视化卵巢和输卵管)或谁是卵巢“钻孔”作为一种程序,以刺激排卵。我们将确定何时何地(根据发育阶段)TGF β生长因子(及其受体靶点)是如何产生的,它们如何在卵巢细胞内发出信号,它们如何与其他生长因子网络相互作用,以及这些过程在正常卵巢和多囊卵巢之间是否存在差异。我们还将在培养的卵巢组织的小样本中检查添加TGF β生长因子的效果。我们希望这些研究不仅能为了解PCOS女性的生育问题提供重要线索,还能为了解PCOS女性的生育问题与代谢紊乱(包括糖尿病)的发展之间的关系提供重要线索。
项目成果
期刊论文数量(10)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Genome-wide association of polycystic ovary syndrome implicates alterations in gonadotropin secretion in European ancestry populations.
- DOI:10.1038/ncomms8502
- 发表时间:2015-08-18
- 期刊:
- 影响因子:16.6
- 作者:Hayes MG;Urbanek M;Ehrmann DA;Armstrong LL;Lee JY;Sisk R;Karaderi T;Barber TM;McCarthy MI;Franks S;Lindgren CM;Welt CK;Diamanti-Kandarakis E;Panidis D;Goodarzi MO;Azziz R;Zhang Y;James RG;Olivier M;Kissebah AH;Reproductive Medicine Network;Stener-Victorin E;Legro RS;Dunaif A
- 通讯作者:Dunaif A
Polycystic ovary syndrome: insight into pathogenesis and a common association with insulin resistance.
- DOI:10.7861/clinmedicine.15-6-s72
- 发表时间:2016-06-01
- 期刊:
- 影响因子:0
- 作者:Barber, Thomas M;Dimitriadis, George K;Franks, Stephen
- 通讯作者:Franks, Stephen
Onset and Heterogeneity of Responsiveness to FSH in Mouse Preantral Follicles in Culture.
- DOI:10.1210/en.2016-1435
- 发表时间:2017-01-01
- 期刊:
- 影响因子:4.8
- 作者:Hardy K;Fenwick M;Mora J;Laird M;Thomson K;Franks S
- 通讯作者:Franks S
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Stephen Franks其他文献
Induction of ovulation with clomiphene citrate in women with polycystic ovary syndrome: the difference between responders and nonresponders.
多囊卵巢综合征女性用克罗米芬柠檬酸盐诱导排卵:有反应者和无反应者之间的差异。
- DOI:
10.1016/s0015-0282(16)60423-5 - 发表时间:
1989 - 期刊:
- 影响因子:6.7
- 作者:
D. Polson;D. Kiddy;H. Mason;Stephen Franks - 通讯作者:
Stephen Franks
Bariatric surgery for spontaneous ovulation in women living with polycystic ovary syndrome: the BAMBINI multicentre, open-label, randomised controlled trial
多囊卵巢综合征女性自发排卵的减肥手术:BAMBINI 多中心、开放标签、随机对照试验
- DOI:
- 发表时间:
2024 - 期刊:
- 影响因子:0
- 作者:
Suhaniya N S Samarasinghe;Bianca Leca;Shahd Alabdulkader;Georgios K. Dimitriadis;Allan Davasgaium;P. Thadani;Kate Parry;Migena Luli;Karen O’Donnell;Brett Johnson;Ali Abbara;Florian Seyfried;Rachel Morman;Ahmed R Ahmed;S. Hakky;Christos Tsironis;Sanjay Purkayastha;C. W. L. Roux;Stephen Franks;Vinod Menon;H. Randeva;Alexander D Miras - 通讯作者:
Alexander D Miras
ZespÛ‡ metaboliczny w zespole policystycznych jajnikÛw
ZespÛ‡ 代谢与 zespole 政策tycznych jajnikÛw
- DOI:
- 发表时间:
2007 - 期刊:
- 影响因子:0
- 作者:
Thomas M. Barber;Mark I. McCarthy;Stephen Franks - 通讯作者:
Stephen Franks
The management of patients with polycystic ovary syndrome
多囊卵巢综合征患者的管理
- DOI:
10.1038/nrendo.2014.102 - 发表时间:
2014-07-15 - 期刊:
- 影响因子:40.000
- 作者:
Channa N. Jayasena;Stephen Franks - 通讯作者:
Stephen Franks
Hypersecretion of luteinizing hormone and ovarian steroids in women with recurrent early miscarriage.
反复早期流产的女性黄体生成素和卵巢类固醇分泌过多。
- DOI:
10.1093/oxfordjournals.humrep.a138149 - 发表时间:
1993 - 期刊:
- 影响因子:6.1
- 作者:
Hazel Watson;D. Kiddy;D. Hamilton‐Fairley;Michael J. Scanlon;Caryl Barnard;William P. Collins;Rosemary C. Bonney;Stephen Franks - 通讯作者:
Stephen Franks
Stephen Franks的其他文献
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{{ truncateString('Stephen Franks', 18)}}的其他基金
Gonadotropin action in the polycystic ovary
促性腺激素在多囊卵巢中的作用
- 批准号:
MR/S025235/1 - 财政年份:2019
- 资助金额:
$ 51.18万 - 项目类别:
Research Grant
The central role for androgens in development of polycystic ovary syndrome
雄激素在多囊卵巢综合征发展中的核心作用
- 批准号:
G0802782/1 - 财政年份:2010
- 资助金额:
$ 51.18万 - 项目类别:
Research Grant
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