Abstract

Examine the relationship between parturition and maternal inflammation, metabolome, proteome, vaginal microbiome, and mechanobiological changes in the cervix during pregnancy. Pregnant women were recruited from the University of California, San Francisco Hospital. Urine and cervical fluid were collected up to 15 time points, while blood samples were collected at three time points during pregnancy. Deep molecular profiling was performed at the multi-omics level, including immune panels, metabolomics, lipidomics, proteomics, and vaginal microbiome. During the same visits that the samples were collected for the multi -omics studies, a unique device called the Smart Diaphragm was used to measure fluorescence and electrical impedance of the cervical tissue. Of the 36 women who completed the study, 34 women had a delivery >37 weeks. A total of 87 blood samples, 327 urine, and 332 swab samples were collected. Using untargeted metabolomics, over 10,000 unique metabolic features were detected, in which 245 pregnancy-related metabolic features were identified in the first set of 16 women (FDR < 0.05). Pathway analysis revealed the top altered pathway in pregnancy was a steroid hormone biosynthesis pathway centered on progesterone. In addition, other altered pathways were also discovered, including the primary bile acid biosynthesis pathway. We observed dynamic changes in the biomechanical properties of the cervical tissue properties during pregnancy (12,013 fluorescence (across 17 wavelengths) and 18,252 impedance measurements (over 10 channels)). In 6 subjects, signal across all spectra decreased dramatically toward the end of the pregnancy. In other subjects, the signal was mostly stable except for some variable changes in early pregnancy. Interestingly, we found five subsets of impedance behaviors, including consistently low impedance (n= 6), spikes immediately prior to labor (n=8), spikes mid-pregnancy and immediately prior to labor (n=7), spikes early in pregnancy (n=5), and consistent spikes (n=9). In this study, we performed multi-omics profiling on samples of 36 women seen at UCSF during their pregnancies. The complete multi-omics profiles and cervical device data analysis reveal novel signatures associated with parturition, which will help explore physiological changes in pregnancy.

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