P-246 Exposure to oral contraceptives alters human endometrial stem cells culture media metabolomics
Authors: Cordeiro F , Lo Turco E , Cellin Rochetti R , Berioni L , Do Vale Teixeira da Costa L , Perkel K J , Fraietta R , Prado F 
Published: June 2023

Abstract

Study question
Can oral contraceptives (OCs) influence the metabolism of endometrial stem cells (EnMSC)?

Summary answer
Altered metabolomic profiling in culture media may be an effect of OC hormonal properties on EnMSC metabolism.

What is known already
The reconstitution of the endometrial tissue relies on the presence of EnMSC, which reside in the perivascular space in the endometrium. This process can be affected by OCs by decreasing the secretory potential of the glands. In case of high dose OCs, hyperplasia of endometrial vessels and stroma atrophy of the glands may occur. However, the precise effect of OCs on the production and metabolism of EnMSCs remains unknown.

Study design, size, duration
This was a prospective study that included samples of menstrual blood from 5 volunteers. The study was conducted for one year and received approval from Ethics in Research Committee. Written informed consent was obtained from all participants.

Participants/materials, setting, methods
Five women with regular menstrual cycles were included in two groups according to the use of OCs: OC (n = 2) and non-OC (n = 3). Samples were collected by the menstrual cup on the second day of the menstrual cycle. The culture medium of EnMSC was collected from each passage. Quantitative metabolomics was performed by multiple reaction monitoring, followed by liquid chromatography mass spectrometry. Data was analyzed by PLS-DA and T-test. Potential biomarkers were assessed by ROC curve.

Main results and the role of chance
The cells were characterized as mesenchymal stem cells with a range of 47,4% to 85% of positive markers. From 186 metabolites quantified in the culture media of OC and non-OC groups, 15 metabolites were proposed as of high discrimination between groups by the PLS-DA, which also demonstrated a total groups separation on the statistical model. The ROC curve showed that 4 out of 15 metabolites presented more than 80% of sensitivity. These metabolites are Alanine, Phosphatidylcholine (PC) aa C30:0, Glycine and PC aa C32:2, whose concentrations were higher in the OC group than in non-OC group. The Students’ T-Test analysis confirmed that the metabolites with higher discrimination between groups presented significant p values. These metabolites have been associated with several metabolic processes, including energy production and alteration of molecular pathways related to thrombosis and cancer.

Limitations, reasons for caution
This study was conducted with a small number of participants and further studies are necessary to confirm the findings.

Wider implications of the findings
The use of OCs could affect endometrial characteristics that are crucial for reproductive success, such as endometrial receptivity. This study provides a preliminary insight into the EnMSCs response to OCs based on specific metabolite signatures, which may contribute to the development of future new reproductive therapies.

Trial registration number
Foundation for Coordination of Higher Education Personnel (CAPES – Brazil).