ESA-SRB-AOTA 2019

Obesity does not impact on endometrial gene expression in women with endometriosis (#717)

Sarah J Holdsworth-Carson 1 , Jessica Chung 2 , Martin Healey 1 , Jenny N Fung 3 , Sally Mortlock 3 , Grant Montgomery 3 , Peter Rogers 1 , Jane E Girling 4
  1. Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, VIC, Australia
  2. Melbourne Bioinformatics, University of Melbourne, Parkville, VIC, Australia
  3. Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia
  4. Department of Anatomy, University of Otago, Dunedin, New Zealand

INTRODUCTION:  Obese women have a reduced incidence of endometriosis.  We recently determined that while the incidence was lower in obese women, they had more severe endometriosis compared to women with lower BMIs and were also diagnosed with significantly less stage I disease.  Endometriosis is considered a disease of endometrial origin; therefore, it is of interest to study endometrial gene expression in studies pertaining to endometriosis. 

Our aims were to determine:

1) in obese women with endometriosis (all stages), does the endometrium demonstrate differential gene expression relative to women with endometriosis and a lower BMI, and

2) in obese women with stage I endometriosis, does the endometrium demonstrate differential gene expression compared to women with lower BMIs who also have stage I disease?

 

METHODS: Endometriosis was diagnosed following surgical and histopathological confirmation.  Women were grouped by BMI (kg/m2).  Total endometrial RNA was extracted and whole-transcriptome sequencing (RNA-Seq) was performed (Illumina TruSeq Stranded Total RNA protocol).  Following multiple testing correction (including for menstrual cycle stage), genes with an adjusted P value (false discovery rate) less than 0.05 were deemed differentially expressed.

 

RESULTS:  Endometrial gene expression from obese women with endometriosis (n=14) were compared to women with endometriosis and underweight (n=6), normal (n=69) and pre-obese (n=30) BMIs; no significant differential gene expression between groups was observed.  We limited the analysis to women with stage I endometriosis (underweight n=5, pre-obese n=18, normal n=41 versus obese n=6); no significant differences were observed when obese women were compared to the lower BMIs. 

 

CONCLUSIONS:  Obesity has negative consequences on endometrial pathologies (including endometrial cancer and infertility).  However, with respect to endometriosis (all stages and stage I alone), we conclude that obesity does not impact on endometrial gene expression.  Future research will need to look beyond the endometrium to determine the influence of obesity on endometriosis disease mechanisms.