Reproductive Medicine Center, Xiangya Hospital of Central South University, Changsha, P.R. China.
Clinical Research Center for Women's Reproductive Health in Hunan Province, Changsha, P.R. China.
Hum Reprod Update. 2022 Nov 2;28(6):858-889. doi: 10.1093/humupd/dmac026.
Obesity has now been recognized as a high-risk factor for reproductive health. Although remarkable advancements have been made in ART, a considerable number of infertile obese women still suffer from serial implantation failure, despite the high quality of embryos transferred. Although obesity has long been known to exert various deleterious effects on female fertility, the underlying mechanisms, especially the roles of lipid metabolism in endometrial receptivity, remain largely elusive.
This review summarizes current evidence on the impacts of several major lipids and lipid-derived mediators on the embryonic implantation process. Emerging methods for evaluating endometrial receptivity, for example transcriptomic and lipidomic analysis, are also discussed.
The PubMed and Embase databases were searched using the following keywords: (lipid or fatty acid or prostaglandin or phospholipid or sphingolipid or endocannabinoid or lysophosphatidic acid or cholesterol or progesterone or estrogen or transcriptomic or lipidomic or obesity or dyslipidemia or polycystic ovary syndrome) AND (endometrial receptivity or uterine receptivity or embryo implantation or assisted reproductive technology or in vitro fertilization or embryo transfer). A comprehensive literature search was performed on the roles of lipid-related metabolic pathways in embryo implantation published between January 1970 and March 2022. Only studies with original data and reviews published in English were included in this review. Additional information was obtained from references cited in the articles resulting from the literature search.
Recent studies have shown that a fatty acids-related pro-inflammatory response in the embryo-endometrium boundary facilitates pregnancy via mediation of prostaglandin signaling. Phospholipid-derived mediators, for example endocannabinoids, lysophosphatidic acid and sphingosine-1-phosphate, are associated with endometrial receptivity, embryo spacing and decidualization based on evidence from both animal and human studies. Progesterone and estrogen are two cholesterol-derived steroid hormones that synergistically mediate the structural and functional alterations in the uterus ready for blastocyst implantation. Variations in serum cholesterol profiles throughout the menstrual cycle imply a demand for steroidogenesis at the time of window of implantation (WOI). Since 2002, endometrial transcriptomic analysis has been serving as a diagnostic tool for WOI dating. Numerous genes that govern lipid homeostasis have been identified and, based on specific alterations of lipidomic signatures differentially expressed in WOI, lipidomic analysis of endometrial fluid provides a possibility for non-invasive diagnosis of lipids alterations during the WOI.
Given that lipid metabolic dysregulation potentially plays a role in infertility, a better understanding of lipid metabolism could have significant clinical implications for the diagnosis and treatment of female reproductive disorders.
肥胖已被确认为生殖健康的高危因素。尽管辅助生殖技术（ART）取得了显著进展，但仍有相当数量的肥胖不孕妇女尽管移植了高质量的胚胎，仍反复着床失败。尽管肥胖对女性生育力有多种有害影响已广为人知，但其中的潜在机制，尤其是脂质代谢在子宫内膜容受性中的作用，仍很大程度上难以捉摸。
本综述总结了目前关于几种主要脂质及其衍生介质对胚胎着床过程影响的证据。还讨论了评估子宫内膜容受性的新兴方法，例如转录组学和脂质组学分析。
使用以下关键词在 PubMed 和 Embase 数据库中进行搜索：（脂质或脂肪酸或前列腺素或磷脂或鞘脂或大麻素或溶血磷脂酸或胆固醇或孕酮或雌激素或转录组学或脂质组学或肥胖或血脂异常或多囊卵巢综合征）和（子宫内膜容受性或子宫容受性或胚胎着床或辅助生殖技术或体外受精或胚胎移植）。对 1970 年 1 月至 2022 年 3 月期间发表的关于胚胎着床过程中脂质相关代谢途径作用的文献进行了全面检索。本综述仅纳入了具有原始数据的研究和以英语发表的综述。从文献检索结果中引用的参考文献中获取了更多信息。
最近的研究表明，胚胎-子宫内膜边界处与脂肪酸相关的促炎反应通过介导前列腺素信号促进妊娠。基于动物和人体研究的证据，磷脂衍生的介质，例如大麻素、溶血磷脂酸和鞘氨醇-1-磷酸，与子宫内膜容受性、胚胎间隔和蜕膜化有关。孕酮和雌激素是两种胆固醇衍生的甾体激素，它们协同介导子宫为胚泡着床做准备的结构和功能改变。整个月经周期中血清胆固醇谱的变化意味着在着床窗口期（WOI）时需要类固醇生成。自 2002 年以来，子宫内膜转录组学分析一直被用作 WOI 日期的诊断工具。已经鉴定出许多控制脂质稳态的基因，并且基于 WOI 中差异表达的脂质组学特征的特定改变，子宫内膜液的脂质组学分析为 WOI 期间脂质改变的非侵入性诊断提供了可能性。
鉴于脂质代谢失调可能在不孕中起作用，更好地了解脂质代谢可能对女性生殖障碍的诊断和治疗具有重要的临床意义。
