Proteomic predictors of serum anti-müllerian hormone levels

Anti-Müllerian hormone (AMH), a marker of ovarian reserve, is associated with time to menopause, fertility, and certain adverse gynecologic conditions. Few studies have evaluated proteins associated with AMH levels. Therefore, the purpose of this study was to use an untargeted proteomic wide association analysis to identify proteins associated with serum AMH levels. A sample of women firefighters enrolled in the Fire Fighter Cancer Cohort Study were included in the analysis ( n = 142). Serum samples were sent for proteomic and AMH analysis. Linear regression models estimating the association of AMH with untargeted proteomics were conducted adjusting for age, body mass index (BMI) (continuous), race, firefighter status, region, and post-traumatic stress disorder (PTSD) diagnosis. A pathway analysis using Gene Set Enrichment Analysis (GSEA) was conducted to identify statistically significantly enriched pathways associated with AMH outcomes using effective size-ranked protein sets. The analysis was performed using the gseGO and gseKEGG functions in the R package clusterProfiler for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, respectively. The average age of participants was 34.1 years (6.2 SD), with the majority being white (83.9%) non-Hispanic (82.8%). Ten proteins (TENM4, SIRT6, AZIN1, NCR3, CGA|FSHB, TPSG1, TNFRSF14, ADAM11, TSSK2, IL22RA1) were observed to be inversely associated with AMH and one protein (BTD) was positively associated with AMH. CGA|FSHB is involved in ovarian follicle development and regulation. TSSK2 has recently been identified in mouse ovarian follicles. TENM4, SIRT6, AZIN1, IL-22RA1 are associated with ovarian function. NCR3, TPSG1, TNFRSF14, and ADAM11 are involved in immune function. BTD plays a role in the regulation of gene expression. Pathways involved in hormone regulation, immune signaling, and metabolic activity were significantly enriched. Our study identified previously known (CGA|FSHB ) and novel proteomic associations with serum AMH levels. These findings provide insight into protein and biological pathways associated with AMH levels. Further research among a larger sample is needed to corroborate these findings.