Exploring the Plasma Proteome Linked to Corpus Luteum Presence and Conception Mode Across Pregnancy Stages and Postpartum

Observational data suggest that women conceiving without a corpus luteum are at higher risk of developing preeclampsia. While the underlying mechanisms remain unclear, the absence of corpus luteum-derived secretory products may be a contributing factor. This study investigates whether the plasma proteome differs between women who conceive with or without a corpus luteum and examines the relationship with mode of conception. Plasma samples from 12 participants were collected at three time points: first trimester, third trimester, and postpartum. The cohort included women who conceived unassisted (UC) after infertility, via artificial cycle frozen embryo transfer (AC FET), or natural cycle frozen embryo transfer (NC FET). 36 plasma protein samples were analyzed using mass spectrometry-based proteomics to compare the proteome of women who conceived with and without a corpus luteum, across different conception methods and pregnancy stages. In total, 528 proteins were quantified. No differentially expressed plasma proteins were identified between women with and without a corpus luteum. However, 15 proteins showed differential expression between UC and FET at all time points, with Bonferroni-corrected p<9.47 × 10E-5 and FC≥|2|. Several altered proteins, including PAPPA and ANG, were linked to preeclampsia. SERPINA7 was differentially detected when comparing time points within the unassisted conception method. No significant differences were detected between AC FET and NC FET. This pilot study revealed a unique proteomic signature associated with mode of conception. The findings suggest biologically plausible candidate proteins for further testing. Validation in larger cohorts or with alternative proteome analysis technologies is needed

观察性研究数据显示，未拥有黄体（corpus luteum）的受孕女性发生子痫前期（preeclampsia）的风险更高。尽管其潜在发病机制尚未明确，但黄体来源的分泌产物缺失可能是相关致病因素之一。本研究旨在探讨拥有与未拥有黄体的受孕女性血浆蛋白质组（plasma proteome）是否存在差异，并分析其与受孕方式的关联。本研究共纳入12名受试者，分别于妊娠早期（first trimester）、妊娠晚期（third trimester）及产后三个时间点采集血浆样本。该队列涵盖三类女性：不孕症经自然受孕（unassisted conception, UC）者、人工周期冷冻胚胎移植（artificial cycle frozen embryo transfer, AC FET）受孕者，以及自然周期冷冻胚胎移植（natural cycle frozen embryo transfer, NC FET）受孕者。采用基于质谱的蛋白质组学（mass spectrometry-based proteomics）技术，对36份血浆蛋白样本进行分析，以比较不同受孕方式及妊娠阶段下，拥有与未拥有黄体的受孕女性的血浆蛋白质组差异。本次研究共定量到528种蛋白质。未在拥有与未拥有黄体的女性中检测到差异表达的血浆蛋白。但在所有时间点中，自然受孕组与冷冻胚胎移植组间共检测到15种差异表达蛋白，经Bonferroni校正后的P值小于9.47×10^-5，且倍数变化（fold change, FC）≥|2|。部分差异表达蛋白（包括PAPPA与ANG）与子痫前期存在关联。在自然受孕组内部比较不同时间点时，检测到SERPINA7的表达存在差异。人工周期与自然周期冷冻胚胎移植组间未检测到显著差异。本先导研究揭示了与受孕方式相关的独特蛋白质组特征。研究结果提示了若干具有生物学合理性的候选蛋白，可供后续验证研究使用。后续仍需在更大规模队列中或采用其他蛋白质组分析技术对该结果进行验证。