Oral Presentation ESA-SRB-NZSE-CaSR 2026 in conjunction with ENSA

Altered basolateral secretions of eutopic endometrial epithelial organoids reflect a dysregulated hormone response in defined clinical stages of endometriosis. (144019)

Jenna Douglas 1 2 , Ralf Schittenhelm 3 , Han Lee 3 , Shanti Gurung 1 2 , Caroline Gargett 1 2 , Beverley Vollenhoven 2 , Harriet Fitzgerald 1 2
  1. Hudson Institute of Medical Research, Clayton, VIC, Australia
  2. Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC, Australia
  3. Proteomics and Metabolomics Platform, Monash University, Clayton, Victoria, Australia

Background
The inner uterine lining, the endometrium, completely remodels in response to menstrual cycle hormones. Endometriosis is a chronic, debilitating gynaecological disorder that affects more than 10% of women (1), with infertility affecting 30-50% of cases (2) likely due to disruptions in hormone-driven processes critical for endometrial receptivity and embryo implantation. The underlying mechanisms of endometriosis-associated infertility remain largely unknown. We aimed to investigate the impact of endometriosis on the hormonal regulation of endometrial epithelia and their secreted products using endometrial epithelial organoids (EEO).

Methods
Eutopic EEO from patients diagnosed with minimal-mild (stages I-II, n=7), moderate-severe (stages III-IV, n=5) and without endometriosis (control, n=7) were treated with either vehicle control, 17β-estradiol (E2) (proliferative phase mimic), or E2 and medroxyprogesterone acetate (MPA) (secretory phase mimic). Hormone receptors PGR, ESR1 and ESR2 in EEO were examined by RT-qPCR and in full-thickness hysterectomy tissue by immunofluorescence. The basolateral secreted proteome of hormone-treated EEO was analysed by mass spectrometry.

Results
PGR expression in EEO resembled in vivo cycle phase-dependent patterns from controls (p<0.05) and stage I-II endometriosis (p<0.01), but not stage III-IV endometriosis. Glandular PGR and ESR1 localisation were sustained in secretory phase endometrium from endometriosis patients but not control patients. 167 significantly (P<0.05, Fold Change >2.0, <-2.0) differentially abundant secreted proteins were identified overall across hormone treatments and groups of endometriosis severity, including RARRES2 (FC=2.64, p<0.05), ANXA1 (FC=1.7, p<0.05) and PAMR1 (FC=-6.78, p<0.05).

Conclusion
EEO from endometriosis patients demonstrate an impaired hormone response, leading to altered steroid hormone receptor expression and localisation and an aberrant secreted proteome in endometriosis patients, with stage-specific differences. These findings provide new insights into the hormonal regulation of eutopic endometrial epithelia across stages of endometriosis severity, facilitating the future development of treatments for endometriosis-associated infertility.

 

  1. Health AIo, Welfare. Endometriosis. Canberra: AIHW; 2023.
  2. Prescott J, Farland LV, Tobias DK, Gaskins AJ, Spiegelman D, Chavarro JE, et al. A prospective cohort study of endometriosis and subsequent risk of infertility. Human Reproduction. 2016;31(7):1475- 82