Concentrations of the endocannabinoid N-arachidonoylethanolamine in the follicular fluid of women with endometriosis: the role of M1 polarised macrophages
Bruno M. Fonseca
A D , Beatriz Moreira-Pinto A , Lia Costa A B , Eduarda Felgueira B , Pedro Oliveira C and Irene Rebelo A
+ Author Affiliations
- Author Affiliations
A UCIBIO, REQUIMTE, Laboratório de Bioquímica, Departamento de Ciências Biológicas, Faculdade de Farmácia da Universidade do Porto, Rua de Jorge Viterbo Ferreira no. 228 4050-313 Porto, Portugal.
B Unidade de Medicina da Reprodução Dra. Ingeborg Chaves, Centro Hospitalar de Vila Nova de Gaia, Espinho, Portugal.
C Unidade de Investigação em Epidemiologia (EPIUnit), Departamento de Estudo de Populações, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.
D Corresponding author. Email: brunofonseca@ff.up.pt
Reproduction, Fertility and Development 33(4) 270-278 https://doi.org/10.1071/RD20247
Submitted: 24 September 2020 Accepted: 6 November 2020 Published: 8 February 2021
Abstract
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 2.5 nM respectively), but not women with tubal, hormonal or unexplained infertility (1.6, 2.4 and 1.9 nM 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.
Keywords: assisted reproductive technology, endocrinology, endometrium, inflammation.
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