PA03_01 - Somatic cell heterogeneity in the human ovarian follicle is associated with sensitivity to follicle stimulating hormone and influenced by endocrine-disrupting chemicals

PA03_01

Somatic cell heterogeneity in the human ovarian follicle is associated with sensitivity to follicle stimulating hormone and influenced by endocrine-disrupting chemicals

A. Velthut-Meikas^1,*

¹Department of Chemistry and Biotechnology, Tallinn University of Technology, Tallinn, Estonia

 

Abstract: Human contact with various endocrine-disrupting chemicals (EDCs) in everyday living environment is inevitable. This chronic exposure with EDCs leads to several adverse health outcomes, including infertility, with a lot of evidence from model organisms and cohort studies involving male participants. The effect that EDCs may pose on female fertility and ovarian function are less understood. Ovaries, as endocrine organs, are potential targets for EDCs, affecting both, female fertility, via their potential direct effect on the oocytes, and overall health, by influencing the steroid-producing somatic cell populations in the ovarian follicle.     

By recruiting 333 female patients from infertility clinics and collecting samples from their ovarian follicles – the environment of oocyte maturation, we have been able to provide a better understanding, whether the most prevalent EDCs in the environment also reach the ovary. We demonstrate that some of the detected EDCs affect IVF outcome, focussing on the sensitivity of ovaries to respond to follicle stimulating hormone (FSH) that is required for follicle growth and oocyte maturation.  

Follicular fluid (FF) and somatic cell samples from 96 follicles containing either high (mean 7.7 ± SD 2.3 nM) or low (0.8 ± 0.4 nM) levels of the plasticizer di(2-ethylhexyl) phthalate (DEHP) metabolites were chosen to reveal molecular mechanisms underlying ovarian dysfunction. RNA-seq from the somatic cells was performed to interpret changes in molecular signalling mechanisms and cell population proportion differences in the follicles under varying exposure conditions. Small RNA-seq from FF was employed to describe differences in intercellular signalling within the follicle and the levels of a panel of 15 steroids hormones was measured.

As a conclusion, we confirmed diminished cholesterol metabolism and steroidogenic potential in the somatic cells and revealed increased inflammatory queues in the follicles containing high levels of DEHP.

Disclosure of Interest: None declared