{"title":"脂质组学揭示了多囊卵巢综合征、复发性自然流产和不孕症的共同机制：一项基于遗传的分析。","authors":"Ailin Tao, Tianqiang Wu, Xinyu Han, Dingren Niu, Xiaoling Feng","doi":"10.2147/IJWH.S514221","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovary syndrome (PCOS), infertility, and recurrent spontaneous abortion (RSA) pose significant challenges to women's reproductive health. While dyslipidemia plays a critical role in these conditions, the causal relationships between specific lipids and these pathologies, as well as their shared mechanisms, remain unclear.</p><p><strong>Methods: </strong>We conducted genome-wide association studies (GWAS) to identify genetic variants associated with 179 plasma lipid species and obtained outcome data for PCOS, infertility, and RSA from the FinnGen R10 database. Mendelian randomization (MR) was performed with genetic variants as instrumental variables (IVs) to assess causal relationships. The inverse variance weighted (IVW) method was the primary approach in our two-sample MR study. Robustness was validated through assessments of heterogeneity, pleiotropy, and leave-one-out analyses.</p><p><strong>Results: </strong>IVW analysis identified 17 plasma lipid species significantly associated with PCOS risk (P < 0.05), including sphingomyelin (d38:2) (OR = 0.909, 95% CI: 0.835-0.990, P = 0.0277) and triacylglycerol (48:2) (OR = 1.291, 95% CI: 1.097-1.518, P = 0.0020). Similarly, 15 lipid species were significantly associated with infertility risk (P < 0.05), such as sphingomyelin (d36:2) (OR = 0.926, 95% CI: 0.888-0.966, P = 0.0003) and triacylglycerol (48:2) (OR = 1.122, 95% CI: 1.059-1.188, P < 0.0001). Two lipid species, phosphatidylinositol (18:0_20:4) (OR = 0.790, 95% CI: 0.693-0.900, P = 0.0004) and sphingomyelin (d42:2) (OR = 0.779, 95% CI: 0.672-0.903, P = 0.0009), showed significant inverse associations with RSA risk, suggesting protective effects.</p><p><strong>Conclusion: </strong>This study establishes causal relationships between specific lipid species and the risk of PCOS, infertility, and RSA, emphasizing lipid metabolism dysregulation as a common pathological mechanism underlying these reproductive disorders. Targeting lipids may offer a promising therapeutic strategy for these diseases.</p>","PeriodicalId":14356,"journal":{"name":"International Journal of Women's Health","volume":"17 ","pages":"1055-1065"},"PeriodicalIF":2.5000,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12005215/pdf/","citationCount":"0","resultStr":"{\"title\":\"Lipidomics Reveals Common Mechanisms in Polycystic Ovarian Syndrome, Recurrent Spontaneous Abortion, and Infertility: A Genetic-Based Analysis.\",\"authors\":\"Ailin Tao, Tianqiang Wu, Xinyu Han, Dingren Niu, Xiaoling Feng\",\"doi\":\"10.2147/IJWH.S514221\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Polycystic ovary syndrome (PCOS), infertility, and recurrent spontaneous abortion (RSA) pose significant challenges to women's reproductive health. While dyslipidemia plays a critical role in these conditions, the causal relationships between specific lipids and these pathologies, as well as their shared mechanisms, remain unclear.</p><p><strong>Methods: </strong>We conducted genome-wide association studies (GWAS) to identify genetic variants associated with 179 plasma lipid species and obtained outcome data for PCOS, infertility, and RSA from the FinnGen R10 database. Mendelian randomization (MR) was performed with genetic variants as instrumental variables (IVs) to assess causal relationships. The inverse variance weighted (IVW) method was the primary approach in our two-sample MR study. Robustness was validated through assessments of heterogeneity, pleiotropy, and leave-one-out analyses.</p><p><strong>Results: </strong>IVW analysis identified 17 plasma lipid species significantly associated with PCOS risk (P < 0.05), including sphingomyelin (d38:2) (OR = 0.909, 95% CI: 0.835-0.990, P = 0.0277) and triacylglycerol (48:2) (OR = 1.291, 95% CI: 1.097-1.518, P = 0.0020). Similarly, 15 lipid species were significantly associated with infertility risk (P < 0.05), such as sphingomyelin (d36:2) (OR = 0.926, 95% CI: 0.888-0.966, P = 0.0003) and triacylglycerol (48:2) (OR = 1.122, 95% CI: 1.059-1.188, P < 0.0001). Two lipid species, phosphatidylinositol (18:0_20:4) (OR = 0.790, 95% CI: 0.693-0.900, P = 0.0004) and sphingomyelin (d42:2) (OR = 0.779, 95% CI: 0.672-0.903, P = 0.0009), showed significant inverse associations with RSA risk, suggesting protective effects.</p><p><strong>Conclusion: </strong>This study establishes causal relationships between specific lipid species and the risk of PCOS, infertility, and RSA, emphasizing lipid metabolism dysregulation as a common pathological mechanism underlying these reproductive disorders. Targeting lipids may offer a promising therapeutic strategy for these diseases.</p>\",\"PeriodicalId\":14356,\"journal\":{\"name\":\"International Journal of Women's Health\",\"volume\":\"17 \",\"pages\":\"1055-1065\"},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2025-04-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12005215/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Women's Health\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2147/IJWH.S514221\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"OBSTETRICS & GYNECOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Women's Health","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/IJWH.S514221","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"OBSTETRICS & GYNECOLOGY","Score":null,"Total":0}
Lipidomics Reveals Common Mechanisms in Polycystic Ovarian Syndrome, Recurrent Spontaneous Abortion, and Infertility: A Genetic-Based Analysis.
Background: Polycystic ovary syndrome (PCOS), infertility, and recurrent spontaneous abortion (RSA) pose significant challenges to women's reproductive health. While dyslipidemia plays a critical role in these conditions, the causal relationships between specific lipids and these pathologies, as well as their shared mechanisms, remain unclear.
Methods: We conducted genome-wide association studies (GWAS) to identify genetic variants associated with 179 plasma lipid species and obtained outcome data for PCOS, infertility, and RSA from the FinnGen R10 database. Mendelian randomization (MR) was performed with genetic variants as instrumental variables (IVs) to assess causal relationships. The inverse variance weighted (IVW) method was the primary approach in our two-sample MR study. Robustness was validated through assessments of heterogeneity, pleiotropy, and leave-one-out analyses.
Results: IVW analysis identified 17 plasma lipid species significantly associated with PCOS risk (P < 0.05), including sphingomyelin (d38:2) (OR = 0.909, 95% CI: 0.835-0.990, P = 0.0277) and triacylglycerol (48:2) (OR = 1.291, 95% CI: 1.097-1.518, P = 0.0020). Similarly, 15 lipid species were significantly associated with infertility risk (P < 0.05), such as sphingomyelin (d36:2) (OR = 0.926, 95% CI: 0.888-0.966, P = 0.0003) and triacylglycerol (48:2) (OR = 1.122, 95% CI: 1.059-1.188, P < 0.0001). Two lipid species, phosphatidylinositol (18:0_20:4) (OR = 0.790, 95% CI: 0.693-0.900, P = 0.0004) and sphingomyelin (d42:2) (OR = 0.779, 95% CI: 0.672-0.903, P = 0.0009), showed significant inverse associations with RSA risk, suggesting protective effects.
Conclusion: This study establishes causal relationships between specific lipid species and the risk of PCOS, infertility, and RSA, emphasizing lipid metabolism dysregulation as a common pathological mechanism underlying these reproductive disorders. Targeting lipids may offer a promising therapeutic strategy for these diseases.
期刊介绍：
International Journal of Women''s Health is an international, peer-reviewed, open access, online journal. Publishing original research, reports, editorials, reviews and commentaries on all aspects of women''s healthcare including gynecology, obstetrics, and breast cancer. Subject areas include: Chronic conditions including cancers of various organs specific and not specific to women Migraine, headaches, arthritis, osteoporosis Endocrine and autoimmune syndromes - asthma, multiple sclerosis, lupus, diabetes Sexual and reproductive health including fertility patterns and emerging technologies to address infertility Infectious disease with chronic sequelae including HIV/AIDS, HPV, PID, and other STDs Psychological and psychosocial conditions - depression across the life span, substance abuse, domestic violence Health maintenance among aging females - factors affecting the quality of life including physical, social and mental issues Avenues for health promotion and disease prevention across the life span Male vs female incidence comparisons for conditions that affect both genders.
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