在生物反应器中长期灌注整个母羊卵巢后的卵巢功能和对促性腺激素的反应。

IF 2.7 3区 医学 Q2 GENETICS & HEREDITY
Prajakta Hatekar, Panagiotis Tsiartas, Lucía de Miguel Gómez, Claudia Mateoiu, Edina Sehic, Mats Hellström, Pasquale Patrizio, Randa Akouri
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引用次数: 0

摘要

目的:对接受促性腺毒性癌症治疗的青春期前女孩和卵巢转移高风险的全身性癌症妇女保留生育能力仍然有限。目前的选择,如卵巢皮质移植,有重新引入恶性细胞的风险。本研究提出了一种新颖的方法,专注于体外卵泡发生和成熟卵母细胞的低温保存,减轻了这种风险。方法:本实验研究优化了绵羊体外卵巢灌注系统,改进促性腺激素刺激以产生成熟卵母细胞。11个卵巢分为2个实验亚组:1组(n = 5)和2组(n = 6)。两组在不同的灌注方案下在生物反应器中灌注4至8天,不同的促性腺激素夜间给药-组1未接受促性腺激素夜间刺激,而组2接受基础促性腺激素夜间刺激。评估包括卵泡增殖、卵母细胞成熟度、细胞凋亡、卵巢功能相关基因表达以及培养基中激素、代谢物和电解质的水平,并在亚组之间进行比较。结果:没有隔夜卵巢刺激的方案产生了成熟的MII卵母细胞,尽管次要卵泡较少且促凋亡BAX基因过表达。相反,经过夜间刺激的卵巢主要产生GV-MI卵母细胞,并表现出次级卵泡增殖减少和更高的HIF1A表达。激素水平、代谢物和电解质在各组和时间内保持稳定。结论:本研究首次报道了在对完整母羊卵巢进行长时间体外灌注后成功收获MII卵母细胞,强调了灌注模型支持晚期卵泡发育的潜力。进一步的研究是必要的,以阐明潜在的机制和完善协议效率。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Ovarian function and response to gonadotropins after prolonged perfusion of whole ewe ovaries in a bioreactor.

Purpose: Fertility preservation for pre-pubertal girls undergoing gonadotoxic cancer treatments and women with systemic cancers at high risk for ovarian metastasis remains limited. Current options, such as ovarian cortex transplantation, risk reintroducing malignant cells. This study presents a novel approach focusing on ex vivo folliculogenesis and mature oocyte retrieval for cryopreservation, mitigating this risk.

Methods: This experimental study optimized an ex vivo ovarian perfusion system in sheep, refining gonadotropin stimulation to yield mature oocytes. Eleven ovaries were divided into two experimental subgroups: Group 1 (n = 5) and Group 2 (n = 6). Both groups were perfused in a bioreactor for 4 to 8 days under distinct perfusion protocols, differing in gonadotropin administration overnight-Group 1 did not receive overnight gonadotropin stimulation, whereas Group 2 received basal gonadotropin stimulation overnight. Assessments included follicular proliferation, oocyte maturity, apoptosis, ovarian function-related gene expression, and the levels of hormones, metabolites, and electrolytes in the culture medium, compared across subgroups.

Results: The protocol without overnight ovarian stimulation yielded mature MII oocytes, despite fewer secondary follicles and overexpression of the pro-apoptotic BAX gene. Conversely, ovaries with overnight stimulation yielded mostly GV-MI oocytes and exhibited reduced secondary follicle proliferation and higher HIF1A expression. Hormone levels, metabolites, and electrolytes remained stable across groups and time.

Conclusions: This study is the first to report the successful harvesting of MII oocytes following extended ex vivo perfusion of intact ewe ovaries, highlighting the potential of the perfusion model to support advanced follicular development. Further investigations are warranted to elucidate underlying mechanisms and refine protocol efficiency.

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来源期刊
CiteScore
5.70
自引率
9.70%
发文量
286
审稿时长
1 months
期刊介绍: The Journal of Assisted Reproduction and Genetics publishes cellular, molecular, genetic, and epigenetic discoveries advancing our understanding of the biology and underlying mechanisms from gametogenesis to offspring health. Special emphasis is placed on the practice and evolution of assisted reproduction technologies (ARTs) with reference to the diagnosis and management of diseases affecting fertility. Our goal is to educate our readership in the translation of basic and clinical discoveries made from human or relevant animal models to the safe and efficacious practice of human ARTs. The scientific rigor and ethical standards embraced by the JARG editorial team ensures a broad international base of expertise guiding the marriage of contemporary clinical research paradigms with basic science discovery. JARG publishes original papers, minireviews, case reports, and opinion pieces often combined into special topic issues that will educate clinicians and scientists with interests in the mechanisms of human development that bear on the treatment of infertility and emerging innovations in human ARTs. The guiding principles of male and female reproductive health impacting pre- and post-conceptional viability and developmental potential are emphasized within the purview of human reproductive health in current and future generations of our species. The journal is published in cooperation with the American Society for Reproductive Medicine, an organization of more than 8,000 physicians, researchers, nurses, technicians and other professionals dedicated to advancing knowledge and expertise in reproductive biology.
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