Poster Presentation ESA-SRB-APEG-NZSE 2022

Relationship between cumulus cell-bound BMP15 and GDF9 in fertility patients (#385)

Adriana E Krysta 1 2 , Angelique H Riepsamen 1 , Aimee SL Walsh 2 , Shelly Lien 1 , Timothy WY Wong 1 , Dulama Richani 1 , Suha Kilani 1 2 , Craig A Harrison 3 , Kylie-ann Mallitt 1 4 , William L Ledger 1 2 , David M Robertson 1 , Robert B Gilchrist 1
  1. Discipline of Women's Health, UNSW Sydney, Sydney, NSW, Australia
  2. IVF Australia, Sydney, NSW, Australia
  3. Monash Biomedicine Discovery Institute, Monash University, Melbourne, Vic, Australia
  4. Centre for Big Data Research in Health, UNSW Sydney, Sydney, NSW, Australia

Bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) are important oocyte-specific paracrine factors which are captured by cumulus cells (CCs) and regulate their function, oocyte quality and ovulation rate. This study aimed to investigate if BMP15/GDF9 bound to CCs can be characterized and quantified, and are associated with IVF outcomes in infertile women. Western blots and novel BMP15 and GDF9 ELISAs were validated and applied to discarded CCs. In study 1, pooled CCs were collected from individual patients (n=200) aged 29-47 years old undergoing superovulation and ICSI. BMP15 and GDF9 levels expressed per CC DNA were retrospectively correlated with clinical data. Western blots showed a number of forms of BMP15/GDF9 on CCs, including high molecular weight precursor forms. Total BMP15 and GDF9 were more closely correlated with total CC DNA than oocyte number, and were highly correlated with each other (r=0.9, p<0.001). BMP15/CC DNA and GDF9/CC DNA were significantly (p<0.05) positively correlated with the number of oocytes/patient. BMP15/CC DNA was negatively associated with maternal age. The BMP15:GDF9 ratio was unrelated to oocyte number or age. In study 2, CCs were collected from 181 individual oocytes from 26 patients and BMP15 and GDF9 levels were correlated with embryo development and pregnancy outcomes following single embryo transfer. BMP15/CC DNA and GDF9/CC DNA were not related to oocyte and embryo outcomes (%GV, %MII, %2PN, %day 3 embryos, %day 5 blastocysts or pregnancy success). However, GDF9/CCDNA and BMP15/CCDNA were highly correlated (r=0.91, p<0.0001) with a significant difference in the BMP15:GDF9 ratio between oocytes generating low- and high-grade blastocysts. This study reports the application of BMP15 and GDF9 ELISAs to human CCs, thus opening the opportunity for their measurement in infertility patients, as a potential novel avenue for a non-invasive diagnostic test of oocyte function and infertility pathologies.