Vale-Fernandes Emídio, Moreira Mafalda V, Rodrigues Bárbara, Pereira Sofia S, Leal Carla, Barreiro Márcia, Tomé António, Monteiro Mariana P
Centre for Medically Assisted Procreation/Public Gamete Bank, Gynaecology Department, Centro Materno-Infantil do Norte Dr. Albino Aroso (CMIN), Unidade Local de Saúde de Santo António (ULSSA), Porto, Portugal.
UMIB - Unit for Multidisciplinary Research in Biomedicine, ICBAS - School of Medicine and Biomedical Sciences, University of Porto, Porto, Portugal.
Front Cell Dev Biol. 2024 Jul 1;12:1408879. doi: 10.3389/fcell.2024.1408879. eCollection 2024.
Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women at childbearing age. Anti-Müllerian hormone (AMH) is a widely accepted sensitive marker of ovarian reserve, which has been suggested that could also act as biomarker of ovarian morphology for PCOS diagnosis. Oxidative stress (OS) is known to be associated and have a negative impact factor in several reproductive conditions, including PCOS. However, the relationship between circulating AMH and OS within the follicular fluid (FF), and its potential impact on fertilization (IVF) outcomes of women with PCOS, remains largely unexplored. A total of 84 women, with PCOS (n = 30) or ovulatory controls (n = 54), were enrolled in this study. Women underwent individualized controlled ovarian stimulation for oocyte retrieval. Blood and FF obtained from mature follicles were collected at the time of oocyte retrieval, for measuring total testosterone, ∆4-androstenedione, progesterone, sex hormone binding globulin (SHBG) and AMH. OS in the FF was assessed by measuring total antioxidant capacity (TAC) through the ferric reducing antioxidant power (FRAP) and lipid peroxidation (LPO) by quantification of malondialdehyde (MDA) levels. Our results demonstrated that women with PCOS had significantly higher plasma levels of AMH, ∆4-androstenedione, total testosterone and a free androgen index (FAI) than observed in non-PCOS controls. In women with PCOS, total testosterone and AMH levels in the FF were also higher, while TAC was lower compared to non-PCOS. Furthermore, circulating AMH levels were positively correlated with ∆4-androstenedione, albeit negatively correlated with TAC. In this study we demonstrated that the susceptibility to OS, as assessed by the total antioxidant capacity in the FF, is higher in women with PCOS and inversely related to AMH levels. This study results lead us to forge the reasonable hypothesis that the greater susceptibility to OS within the follicle microenvironment is potentially at the end of a roadway that starts with elevated ∆4-androstenedione and AMH within the FF, which in turn are mirrored by circulating AMH and androgen levels. Thus, suggesting that circulating AMH levels could act as a surrogate biomarker of follicular fluid oxidative stress in women with PCOS.
多囊卵巢综合征(PCOS)是育龄女性中最常见的内分泌疾病。抗苗勒管激素(AMH)是一种广泛认可的卵巢储备敏感标志物,有人提出它也可作为PCOS诊断中卵巢形态的生物标志物。已知氧化应激(OS)与包括PCOS在内的多种生殖疾病相关且是一个负面因素。然而,卵泡液(FF)中循环AMH与OS之间的关系及其对PCOS女性体外受精(IVF)结局的潜在影响在很大程度上仍未得到探索。本研究共纳入了84名女性,其中PCOS患者30例,排卵正常对照者54例。这些女性接受个体化控制性卵巢刺激以获取卵母细胞。在取卵时收集来自成熟卵泡的血液和卵泡液,用于检测总睾酮、Δ4-雄烯二酮、孕酮、性激素结合球蛋白(SHBG)和AMH。通过铁还原抗氧化能力(FRAP)测定总抗氧化能力(TAC)并通过定量丙二醛(MDA)水平评估卵泡液中的脂质过氧化(LPO),以此来评估卵泡液中的氧化应激。我们的结果表明,PCOS女性的血浆AMH、Δ4-雄烯二酮、总睾酮和游离雄激素指数(FAI)水平显著高于非PCOS对照者。在PCOS女性中,卵泡液中的总睾酮和AMH水平也更高,而与非PCOS女性相比,其总抗氧化能力更低。此外,循环AMH水平与Δ4-雄烯二酮呈正相关,与总抗氧化能力呈负相关。在本研究中我们证明,通过卵泡液中的总抗氧化能力评估,PCOS女性对氧化应激的易感性更高,且与AMH水平呈负相关。本研究结果使我们合理推测,卵泡微环境中对氧化应激更大的易感性可能最终源于卵泡液中升高的Δ4-雄烯二酮和AMH,而循环AMH和雄激素水平又反映了这两者。因此,提示循环AMH水平可能作为PCOS女性卵泡液氧化应激的替代生物标志物。