Laboratory of Clinical Immunology, National Medical Research Center for Obstetrics, Gynecology and Perinatology of Ministry of Healthcare of Russian Federation, Oparina str. 4, Moscow, Russia, 117997.
Department of Assisted Technologies in Treatment of Infertility, National Medical Research Center for Obstetrics, Gynecology and Perinatology of Ministry of Healthcare of Russian Federation, Oparina str. 4, Moscow, Russia, 117997.
Reprod Sci. 2021 Jan;28(1):144-158. doi: 10.1007/s43032-020-00253-z. Epub 2020 Jul 7.
We have previously shown that high level of seminal interleukin (IL)-18 is positively associated with a greater risk of pregnancy failure in women exposed to their partners' seminal plasma (SP) during the in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycle. Since IL-18 and IL-1β considered to be the key immune markers of stress, here we ask whether their increase in SP may be due to the stress experienced by men engaged in the IVF programs. Therefore, we correlated seminal IL-18 with IL-1β and both cytokines with the seminal steroids, whose increase indicates the activation of neuroendocrine stress response systems. Retrospective analysis of stored seminal samples was performed. Based on previously identified cutoff level for content of IL-18 per ejaculate, samples with high IL-18 content from IVF failure group (n = 9), as well as samples with low IL-18 content from IVF success group (n = 7), were included in the study. Seminal cytokines were evaluated using FlowCytomix™ technology. A set of 16 biologically active steroids in SP was quantified by liquid chromatography coupled with mass spectrometry. Concentrations and total amounts per ejaculate of cytokines and steroids were determined. A positive significant correlation was found between the levels of IL-18 and IL-1β. There was also a positive correlation between IL-18 or IL-1β and 17-α-hydroxypregnenolone, 17-α-hydroxyprogesterone, dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), androstenedione, testosterone, dihydrotestosterone, progesterone, corticosterone, 11-deoxycorticosterone, and the ratio of DHEAS/cortisol. We suggested that stress-related overexpression of immune and hormonal factors in SP may be the key link between male stress and embryo implantation failure.
我们之前的研究表明，在体外受精（IVF）/胞浆内单精子注射（ICSI）周期中，女性接触伴侣的精液（SP）时，高浓度的精液白细胞介素（IL）-18 与妊娠失败的风险增加呈正相关。由于 IL-18 和 IL-1β 被认为是应激的关键免疫标志物，因此，我们想知道 SP 中它们的增加是否是由于参与 IVF 项目的男性经历了应激。因此，我们将精液中的 IL-18 与 IL-1β 进行了相关分析，同时将这两种细胞因子与精液类固醇进行了相关分析，因为后者的增加表明神经内分泌应激反应系统被激活。对储存的精液样本进行了回顾性分析。根据之前鉴定的每个射精物中 IL-18 的含量的临界值，从 IVF 失败组（n=9）中选择含有高浓度 IL-18 的样本，以及从 IVF 成功组（n=7）中选择含有低浓度 IL-18 的样本，纳入研究。使用 FlowCytomix™技术评估精液细胞因子。通过液相色谱-串联质谱法定量 SP 中的 16 种具有生物活性的类固醇。确定了细胞因子和类固醇在每个射精物中的浓度和总量。发现 IL-18 和 IL-1β 之间存在显著正相关。IL-18 或 IL-1β 与 17-α-羟孕烯醇酮、17-α-羟基孕酮、脱氢表雄酮（DHEA）、DHEA 硫酸盐（DHEAS）、雄烯二酮、睾酮、二氢睾酮、孕酮、皮质酮、11-脱氧皮质酮和 DHEAS/皮质醇比值之间也存在正相关。我们认为，SP 中与应激相关的免疫和激素因子的过度表达可能是男性应激与胚胎植入失败之间的关键联系。
