Concentrations of the endocannabinoid N-arachidonoylethanolamine in the follicular fluid of women with endometriosis: the role of M1 polarised macrophages

Fonseca et al. ·Reproduction, Fertility and Development Impact 0.4

Unclear 11 citations

SampleSonstige Evidenz

Durationunclear

EndpointAEA concentration

Blindingn.a.

DesignSonstiges

Key finding

Study shows increased AEA concentrations in follicular fluid of women with endometriosis and that M1-polarised macrophages increase AEA production by granulosa cells; therapeutic or clinical effects are not investigated.

Summary

Measurement of anandamide (AEA) in follicular fluid in women with/without endometriosis; exploratory, mechanistic data on endogenous endocannabinoid status, no intervention with cannabis.

PopulationWomen undergoing assisted reproductive technology (ART), including endometriosis, male infertility, tubal/hormonal/unexplained infertility; additionally in-vitro co-culture of human granulosa cells with macrophages

InterventionMeasurement of N-arachidonoylethanolamine (anandamide, AEA) in follicular fluid; in vitro co-culture with M1-polarised macrophages

OutcomeFF-AEA concentrations significantly higher in endometriosis (2,5 nM) vs. male infertility (1,6 nM); M1 macrophages increase AEA production by granulosa cells via NAPE-PLD upregulation

Quality profile

Sample size —

Blinding —

Effect size —

Citations / year ★★★★★

Authors

Fonseca B M, Moreira-Pinto B, Costa L et al.

DOI 10.1071/rd20247↗

Design: Sonstiges

Abstract

Concentrations of the endocannabinoid N-arachidonoylethanolamine in the follicular fluid of women with endometriosis: the role of M1 polarised macrophages. Although N-arachidonoylethanolamine (AEA; also known as anandamide) is present in human follicular fluid (FF), its regulation remains unknown. Therefore, the aims of the present study were to: (1) investigate the relationships between FF AEA concentrations in women undergoing assisted reproductive technology and their age, body mass index, ART characteristics and fertility treatment outcomes; and (2) assess how different inflammatory patterns may trigger AEA production by human granulosa cells (hGCs). FF AEA concentrations were higher in women undergoing IVF than in those undergoing intracytoplasmic sperm injection group. FF AEA median concentrations were lower in women undergoing ART because of male factor infertility than in women with endometriosis (1.6 vs 2.5nM respectively), but not women with tubal, hormonal or unexplained infertility (1.6, 2.4 and 1.9nM respectively). To evaluate the effects of macrophages on AEA production by hGCs, hGCs were cocultured with monocyte-derived macrophages. The conditioned medium from M1 polarised macrophages increased AEA production by hGCs. This was accompanied by an increase in AEA-metabolising enzymes, particularly N-acyl phosphatidylethanolamine-specific phospholipase D. The results of the present study show that high FF AEA concentrations in patients with endometriosis may be associated with the recruitment of inflammatory chemokines within the ovary, which together may contribute to the decreased reproductive potential of women with endometriosis. Collectively, these findings add a new player to the hormone and cytokine networks that regulate fertility in women.

The impediment to action advances action. — Marcus Aurelius