Gao Huajing, Ying Yuewen, Sun Jing, Huang Yun, Li Xue, Zhang Dan
Key Laboratory of Reproductive Genetics (Ministry of Education) and Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China.
Department of Big Data in Health Science, School of Public Health, Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China.
Nutrients. 2024 Nov 28;16(23):4103. doi: 10.3390/nu16234103.
Female reproductive aging remains irreversible. More evidence is needed on how polyunsaturated fatty acids (PUFAs) affect the female reproductive lifespan.
To identify and validate specific PUFAs that can influence the timing of menarche and menopause in women.
We utilized a two-sample Mendelian randomization (MR) framework to evaluate the causal relationships between various PUFAs and female reproductive longevity, defined by age at menarche (AAM) and age at natural menopause (ANM). Our analyses leveraged summary statistics from four genome-wide association studies (GWASs) on the plasma concentrations of 10 plasma PUFAs, including 8866 to 121,633 European individuals and 1361 East Asian individuals. Large-scale GWASs for reproductive traits provided the genetic data of AAM and ANM from over 202,323 European females and 43,861 East Asian females. Causal effects were estimated by beta coefficients, representing, for each increase in the standard deviation (SD) of plasma PUFA concentration, the yearly increase in AAM or ANM. Replications, meta-analyses, and cross-ancestry effects were assessed to validate the inference.
Higher plasma DHA was identified to be associated with delayed natural menopause without affecting menarche, offering a potential intervention target for extending reproductive longevity.
女性生殖衰老不可逆。关于多不饱和脂肪酸（PUFAs）如何影响女性生殖寿命，还需要更多证据。
确定并验证可影响女性初潮和绝经时间的特定多不饱和脂肪酸。
我们采用两样本孟德尔随机化（MR）框架，评估各种多不饱和脂肪酸与女性生殖寿命之间的因果关系，女性生殖寿命由初潮年龄（AAM）和自然绝经年龄（ANM）定义。我们的分析利用了四项全基因组关联研究（GWAS）的汇总统计数据，这些研究涉及10种血浆多不饱和脂肪酸的血浆浓度，包括8866至121,633名欧洲个体和1361名东亚个体。生殖性状的大规模GWAS提供了来自202,323多名欧洲女性和43,861名东亚女性的初潮年龄和自然绝经年龄的遗传数据。因果效应通过β系数估计，代表血浆多不饱和脂肪酸浓度每增加一个标准差（SD），初潮年龄或自然绝经年龄的年增加量。评估复制、荟萃分析和跨祖先效应以验证推断。
较高的血浆DHA被确定与自然绝经延迟相关，而不影响初潮，为延长生殖寿命提供了一个潜在的干预靶点。
