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Aamir Mahmood

 

Aamir Mahmood

The First Affiliated Hospital of Zhengzhou University
China

Abstract Title: Integrative Genomics Identifies Progesterone Receptor Signaling as Protective Against Female Infertility via Immune Modulation: A Mendelian Randomization Study

Biography: Aamir Mahmood completed his bachelor degree of clinical medicine during 2016-2021. He did his master degree of Obstetrics and Gynecology during 2021-2024. Currently, He is PhD student at Henan Key Laboratory of Reproductive and Genetics, The First Affiliated Hospital of Zhengzhou University, China. His Research interests are Ovarian Aging, Primary Ovarian Insufficiency (POI), Polycystic Ovary Syndrome (PCOS), Female reproductive health and fertility, Ovarian biology and disease, Reproductive endocrinology and health.

Research Interest: Progesterone is essential for female reproduction, but the causal relationship between its signaling pathway and infertility remains uncharacterized. We applied a multi-omics Mendelian randomization (MR) framework to investigate the causal effect of progesterone receptor (PGR) signaling on female infertility risk. Genetic instruments for circulating PGR protein levels were obtained from a genome-wide association study (GWAS) of 47,745 individuals. Outcome data came from the FinnGen consortium (18,718 infertility cases, 501,254 controls). Genetic predisposition to higher PGR levels was associated with a reduced risk of female infertility (inverse variance weighted OR = 0.87, 95% CI: 0.76–0.99). Bidirectional MR suggested a potential feedback loop, with genetic liability to infertility associated with lower PGR levels. Multi-tissue expression quantitative trait locus (eQTL) mapping identified 213 significant associations affecting 60 genes. Strikingly, 8 of 12 ovary-specific candidate genes (67%) were located in the HLA/MHC locus. Functional enrichment analysis revealed overwhelming dominance of immune pathways. Protein-protein interaction network analysis highlighted HLA-DRB1, HLA-C, and SIRPB1 as central hubs. This integrative genomic study provides novel evidence that progesterone receptor signaling protects against female infertility primarily through immune modulation mechanisms, with HLA genes playing a central role.