METABOLIC PHENOTYPING IDENTIFIES DISTINCT SYSTEMIC AND FOLLICULAR BILE ACID PROFILES THAT DEPEND ON BODY FAT CONTENT
2Clinical Institute for Medical and Chemical Laboratory Diagnosis (CIMCL), Medical University of Graz, Graz
Problem statement
Cumulative evidence demonstrates that metabolism is a key regulator of reproductive health. Since the prevalence of obesity and associated metabolic disturbances is constantly increasing, a comprehensive approach to assess metabolic risk factors is highly relevant to improve infertility procedures. In this study we analyzed individual metabolic signatures and in particular target systemic and follicular bile acid (BA) profiles of in vitro fertilization (IVF)-patients. BAs, which have been recognised for decades for their fat digestive properties, have gained clinical significance as nuclear receptor ligands that exert multiple (patho)physiological effects. Importantly, the composition of BA as well as total BA levels have been shown to affect follicular maturation and steroidogenesis in different animal models.
Methods
On the day of the follicle puncture for oocyte retrieval, fasting blood was sampled to analyze various blood parameters including blood lipids, glucose metabolism, liver enzyme activities and hormones. Serum and intrafollicular fluids were analyzed by LC-MS/MS. In addition, the individual body composition was analyzed using air displacement plethysmography (BOD POD®).
Results
Our preliminary data revealed an altered composition and concentration of BAs in serum and follicular fluid of patients exhibiting 37- 48% body fat compared to normal distributed (21- 33%) subjects. Notably, this result was independent of BMI, which ranged between 22 and 25 kg/m² in the study group. Particularly, the proportion of chenodeoxycholic acid and deoxycholic acid was increased in patients with high body fat, which were previously shown to be related to oxidative stress, DNA damage and apoptosis, suggesting an adverse effect on follicle development and maturation. In addition, we observed a positive correlation between systemic deoxycholic acid and insulin as well as cholesterol levels of the patients.
Conclusion
Our results indicate that excessive accumulation of body fat affects the intrafollicular environment by significant changes in BA profiles. Moreover, our study highlights the limited use of BMI as diagnostic criteria, as it does not differentiate between fat and lean mass. This study provides an in-depth analysis of IVF-patients and ultimately leads to the discovery of metabotype signatures, which could be used for patient stratifications and lifestyle interventions in the future.
