This is a past event.

Tessa Steenwinkel, PhD Candidate

Department of Pathology & Immunology, Baylor College of Medicine

Abstract:

Polycystic ovary syndrome (PCOS) is the primary cause of anovulatory infertility worldwide. Up to 10% of all women of reproductive age are affected by PCOS and experience hormonal imbalance, excessive androgens, or polycystic ovaries. In addition, PCOS is frequently associated with insulin resistance, obesity, diabetes, and an increased likelihood of developing depression or anxiety. So far, genome-wide association studies have identified many genetic risk loci, including heterozygous polymorphisms in ligands and receptors belonging to the transforming growth factor beta (TGFβ) superfamily. More recently, the Rare and Atypical Diabetes Network (RADIANT) identified a monogenic variant in SMAD5, one of the ligand-activated transcription factors of the TGFβ superfamily, in a woman with atypical diabetes and PCOS. This variant was subsequently found in her daughter who also has PCOS. The
focus of my dissertation research is how this genetic variant alters SMAD5 function and its systemic effect in vivo. To study this, our lab generated the homologous point mutation in SMAD5 in mice using CRISPR/Cas9. In my talk, I will discuss our current work demonstrating that homozygous 
Smad5KI/KI mice have partial sub-lethality and that the heterozygous 
Smad5KI+ mice have alterations in their reproductive and metabolic health. Overall, we show that several key PCOS traits are present in these mice, providing a potentially valuable model to help unravel the molecular mechanisms underlying PCOS in women.