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精子氨基肽酶 N 可识别卵母细胞捐赠周期中高质量的囊胚和可存活胚胎的潜力。

Sperm aminopeptidase N identifies the potential for high-quality blastocysts and viable embryos in oocyte-donation cycles.

机构信息

Department of Physiology, Faculty of Medicine and Nursery, University of the Basque Country (UPV/EHU), Leioa, Bizkaia, Spain.

Innovation in Assisted Reproduction Group, Biocruces-Bizkaia Health Research Institute, Barakaldo, Spain.

出版信息

Hum Reprod. 2022 Sep 30;37(10):2246-2254. doi: 10.1093/humrep/deac170.

Abstract

STUDY QUESTION

Is there a relationship between human sperm aminopeptidase N (APN) and embryo development in humans?

SUMMARY ANSWER

Human sperm APN could possibly become a new molecular biomarker for identifying the potential for high-quality and usable embryos.

WHAT IS KNOWN ALREADY

The diagnosis of male fertility is one of the major concerns of reproductive medicine. Approximately 30-40% of men with otherwise normal fertility parameters are still unable to achieve pregnancy. The predictive clinical value of semen analysis to identify fertile or infertile males is limited; therefore, new diagnostic methodologies for sperm are urgently required. Sperm APN may be a relevant molecular marker due to its high concentration in sperm cells and its important roles in sperm physiology, such as its functions in motility, acrosome reaction and embryo development.

STUDY DESIGN, SIZE, DURATION: This study included 81 couples who underwent oocyte-donation cycles at Clínica IVI Bilbao (Spain), yielding 611 embryos, between September 2014 and July 2015.

PARTICIPANTS/MATERIALS, SETTING, METHODS: This study was conducted in an assisted reproduction unit and an academic research laboratory. All the semen samples were examined and classified following World Health Organization guidelines. Spermatozoa were isolated from semen using the discontinuous colloidal silica gradient (45-90%) technique. Embryo quality and development were determined according to the Spanish Association of Reproduction Biology Studies (ASEBIR) criteria. Human sperm APN levels were analyzed by quantitative and semiquantitative flow cytometry.

MAIN RESULTS AND THE ROLE OF CHANCE

The most well-developed and usable blastocysts were associated with low sperm APN levels. Semen samples that had lower APN levels generated more expanded, hatched and usable blastocysts and fewer early, arrested and non-usable blastocysts. The cumulative probability of having well-developed blastocysts increased by 1.38-fold at Day 5 and 1.90-fold at Day 6 of embryo development, and the likelihood of having usable embryos increased by 1.48-fold, when semen samples with low APN levels were used during the ICSI technique.

LIMITATIONS, REASONS FOR CAUTION: The data were obtained from a single fertility clinic. A multicentre study will be required to confirm the results.

WIDER IMPLICATIONS OF THE FINDINGS

Human sperm APN has the potential to become a new molecular biomarker to help identify the potential for high-quality embryos and diagnose male infertility, especially when seminal parameters are close to the threshold values. It could be a crucial tool for couples for whom the number of usable blastocysts is critical for ART success.

STUDY FUNDING/COMPETING INTEREST(S): This study was supported by grants from the Basque Government (GIC15/165) and the University of the Basque Country (UPV/EHU) (EHUA14/17). The authors declare that they have no conflicts of interest.

TRIAL REGISTRATION NUMBER

N/A.

摘要

研究问题

人类精子氨肽酶 N(APN)与人类胚胎发育之间是否存在关系?

总结答案

人类精子 APN 可能成为鉴定高质量和可用胚胎潜能的新分子生物标志物。

已知情况

男性生育力的诊断是生殖医学的主要关注点之一。大约 30-40%的 otherwise normal fertility parameters 的男性仍然无法怀孕。精液分析对识别有生育能力或不育男性的预测临床价值有限;因此,迫切需要新的精子诊断方法。由于精子 APN 在精子细胞中浓度高,并且在精子生理功能中具有重要作用,例如在运动、顶体反应和胚胎发育中的功能,因此它可能是一个相关的分子标记。

研究设计、大小、持续时间:本研究纳入了 2014 年 9 月至 2015 年 7 月在西班牙比利亚诺瓦 IVI 诊所接受卵母细胞捐赠周期的 81 对夫妇,共产生 611 个胚胎。

参与者/材料、地点、方法:本研究在辅助生殖单位和学术研究实验室进行。所有精液样本均按照世界卫生组织指南进行检查和分类。使用不连续胶体硅梯度(45-90%)技术从精液中分离精子。根据西班牙生殖生物学研究协会(ASEBIR)标准确定胚胎质量和发育。通过定量和半定量流式细胞术分析人精子 APN 水平。

主要结果和机会的作用

最发达和可用的囊胚与低精子 APN 水平相关。APN 水平较低的精液样本产生更多扩张、孵化和可用的囊胚,以及更少的早期、停滞和不可用的囊胚。在使用 ICSI 技术时,当使用 APN 水平较低的精液样本时,胚胎发育第 5 天和第 6 天囊胚发育良好的累积概率分别增加了 1.38 倍和 1.90 倍,可用胚胎的可能性增加了 1.48 倍。

局限性、谨慎的原因:数据来自单一的生育诊所。需要进行多中心研究来证实这些结果。

研究结果的更广泛影响

人类精子 APN 有可能成为一种新的分子生物标志物,有助于识别高质量胚胎的潜力并诊断男性不育症,尤其是在精液参数接近阈值时。对于那些胚胎数量对 ART 成功至关重要的夫妇来说,它可能是一个关键工具。

研究资助/利益冲突:本研究得到巴斯克政府(GIC15/165)和巴斯克大学(UPV/EHU)(EHUA14/17)的资助。作者声明他们没有利益冲突。

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