Faculdade de Veterinária, Universidade Federal Fluminense, Rua Vital Brazil Filho, 64, 24230-340, Niterói, Rio de Janeiro, Brazil.
Faculdade de Veterinária, Universidade Federal Fluminense, Rua Vital Brazil Filho, 64, 24230-340, Niterói, Rio de Janeiro, Brazil.
Theriogenology. 2022 Aug;188:90-99. doi: 10.1016/j.theriogenology.2022.05.023. Epub 2022 Jun 1.
Simulated Physiological Oocyte Maturation (SPOM) mimics in vitro the physiological events of oocyte maturation. The system uses cAMP modulators in two steps (pre IVM and IVM) and has presented promising results that are arousing the curiosity of IVF programs in different animal species, generating several papers, adaptations, and controversies worldwide. This study systematically analyses the data in the literature on the use of SPOM and compares the outcomes to the original paper (Albuz et al. Hum. Rep., 25: 2999-3011 2010), classifying them into success or failure. The PubMed, Scopus, and Google Scholar databases were searched and 22 studies were included, from which data on 26 experiments were extracted and evaluated via descriptive statistical analysis. Only experiments that assessed the blastocyst rate (BR) were considered for the success parameter, i.e. success (increase in BR) or failure (either no difference or a reduction in BR). The experiments applied the SPOM system in the following species: cattle, sheep, goats, mice, mares and cats. Three experiments (3/26) could not be evaluated for success or failure, and of the remaining, 34.7% (8/23) succeeded in improving blastocyst production. More than two-thirds (69.2%, 18/26) of experiments were conducted in cattle; of those, 86.8% (13/15) used TCM-199 as the IVM media, and 22.2% did not use forskolin or IBMX modulators as indicated in the original study. Also, 27.7% (5/18) of the experiments in cattle used the same type and dose of FSH, and 22% (4/18) used the same protein source and concentration as indicated in the original study. All experiments conducted in mice (3) kept the parameters of the original study in terms of forskolin and IBMX doses and BSA and FSH concentrations, however, they removed cilostamide from IVM. Cilostamide was used during IVM in more than half (53.8%) of all experiments, but only in cattle and sheep. Considering oocyte and embryo assessments, six experiments assessed cAMP levels and most (5/6) of these observed an increase: in cattle (2), sheep (2), and mice (1). Ten experiments evaluated the effect of SPOM on nuclear maturation, and in 90% (9/10), the SPOM system was able to arrest meiosis (cattle, sheep and mice). Thirteen experiments evaluated the total cell number (cattle, mice and sheep), and six (6/13) showed an increase. Our findings clearly indicate difficulties in reproducing the SPOM system worldwide, demonstrating that the meiosis arrest is not sufficient to ensure successful SPOM application. They also suggest that the different supplements used in the IVM medium and/or their interaction with modulators for different durations may produce a significant bias that affects experimental success.
模拟生理卵母细胞成熟 (SPOM) 在体外模拟卵母细胞成熟的生理事件。该系统在两步(IVM 前和 IVM 期间)中使用 cAMP 调节剂,并且已经取得了有前景的结果,这引起了不同动物物种的 IVF 计划的兴趣,产生了许多论文、适应和全球范围内的争议。本研究系统地分析了文献中关于 SPOM 使用的数据,并将结果与原始论文(Albuz 等人,Hum. Rep.,25: 2999-3011, 2010)进行比较,将其分类为成功或失败。在 PubMed、Scopus 和 Google Scholar 数据库中进行了搜索,共纳入了 22 项研究,从中提取了 26 项实验的数据,并通过描述性统计分析进行了评估。只有评估囊胚率 (BR) 的实验才被视为成功参数,即成功(BR 增加)或失败(BR 无差异或减少)。该系统已在以下物种中应用:牛、绵羊、山羊、小鼠、母马和猫。有三个实验(3/26)无法评估成功或失败,其余的 23 个实验中有 34.7%(8/23)成功提高了囊胚产量。超过三分之二(69.2%,18/26)的实验是在牛中进行的;其中,86.8%(13/15)使用 TCM-199 作为 IVM 培养基,并且 22.2%(13/59)没有使用原研究中指示的 forskolin 或 IBMX 调节剂。此外,牛中 27.7%(5/18)的实验使用了相同类型和剂量的 FSH,22%(4/18)使用了与原研究相同的蛋白质来源和浓度。在所有在小鼠中进行的实验(3)在 forskolin 和 IBMX 剂量以及 BSA 和 FSH 浓度方面保留了原始研究的参数,但在 IVM 期间去除了 cilostamide。在超过一半(53.8%)的所有实验中使用了 cilostamide 进行 IVM,但仅在牛和绵羊中使用。在卵母细胞和胚胎评估方面,有 6 个实验评估了 cAMP 水平,其中大多数(5/6)观察到增加:在牛(2)、绵羊(2)和小鼠(1)中。有 10 个实验评估了 SPOM 对核成熟的影响,在 90%(9/10)的实验中,SPOM 系统能够阻止减数分裂(牛、绵羊和小鼠)。有 13 个实验评估了总细胞数(牛、小鼠和绵羊),其中 6 个(6/13)显示增加。我们的研究结果清楚地表明,在全球范围内重现 SPOM 系统存在困难,表明减数分裂阻滞不足以确保成功应用 SPOM。它们还表明,在 IVM 培养基中使用的不同补充剂及其与调节剂的不同持续时间的相互作用可能会产生显著偏差,从而影响实验结果。