Poster Presentation ESA-SRB 2023 in conjunction with ENSA

 Changes in endometrial prorenin and the (pro)renin receptor across the menstrual cycle and in early pregnancy (#377)

Tess L Symington 1 2 , Joshua J Fisher 2 3 , Sarah J Delforce 1 2 , Wei Zhou 4 5 , Evdokia Dimitriadis 4 5 , Kirsty G Pringle 1 2
  1. School of Biomedical Science and Pharmacy, University of Newcastle, Newcastle, NSW, Australia
  2. Mothers and Babies Research Program, Hunter Medical Research Institute, Newcastle, NSW, Australia
  3. School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia
  4. Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, Victoria , Australia
  5. Gynaecology Research Centre, Royal Women's Hospital, Parkville, Victoria, Australia

The endometrium is remodelled each menstrual cycle in response to hormonal fluctuations, and, to prepare for embryo implantation, transforms into the decidua. Both prorenin and its receptor, the (pro)renin receptor (PRR), initiators of renin-angiotensin system signalling, are abundant within the endometrium and decidua. Prorenin levels are increased upon decidualisation in vitro; therefore, we aimed to characterise prorenin and PRR expression across the menstrual cycle and in early gestation decidua, hypothesising they could be involved in both.

 

Endometrial biopsies were collected from fertile patients during the proliferative (n=5), mid (n=3), and late (n=5) secretory phases. Early gestation decidua (8-17 weeks) was collected from elective terminations of pregnancy (n=4). Prorenin and PRR proteins were localised using immunohistochemistry and staining intensity (H-score) quantified using HALO image analysis software. qPCR was used to determine mRNA expression of prorenin, PRR and markers of decidualisation in early gestation decidua (n=14).

 

The staining intensity of prorenin in decidual stroma was greater than in non-pregnant, cycling endometrium (P=0.0059), with no changes across the menstrual cycle. Glandular prorenin staining was more intense in mid and late secretory phases compared with the proliferative phase (P=0.042 and P=0.036). Stromal PRR staining intensity did not change across the menstrual cycle, however, was greater in decidua compared with non-pregnant endometrium (P=0.042). Glandular staining for PRR was greater in the mid-secretory phase compared with the proliferative phase (P=0.026). Decidual prorenin and PRR mRNA expression were positively correlated with gestation (8-17 weeks; P<0.001, r=0.65, and P=0.012, r=0.855, respectively), as well as with markers of decidualisation: prolactin (P=0.012, r=0.651 and P=0.0001, r=0.869) and insulin-like growth factor binding protein-1 (P=0.0035, r=0.723 and P<0.0001, r=0.923).

 

Conclusion:

These findings describe the cyclic nature of the renin-angiotensin system in the endometrium, with the increased prorenin and PRR abundance in the decidua suggesting a potential role in decidualisation.