Fig. 1

Expression of ECS enzymes in human fetal testis. RNA-seq quantification of the expression of transcripts encoding AEA synthetizing (A–D) and degrading enzymes (E–G), and 2-AG synthetizing (H–K) and degrading (L–N) enzymes in bulk embryonic human testis from 6 to 17 developmental weeks (DW). Transcript amount is expressed in Fragments Per Kilobase Million (FPKM). Data presented as means + / − SEM. An ANOVA test was performed followed by a Kruskal–Wallis test to compare the transcript at 6 DW with other ages (*, p < 0.05) and a two-stage linear step-up procedure (Benjamini, Krieger and Yekutieli). A schematic representation of endocannabinoid synthesis and degradation pathways is shown. Endocannabinoids derive from membrane phospholipid precursors, phosphatidylethanolamine (PEth), phosphatidylinositol (PI), and arachidonic acid (ARA). The major synthetizing enzymes of AEA are N-acetyltransferase 10 (NAT10) and N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D (NAPE-PLD). The alternative pathway of AEA synthesis involves Abhydrolase domain-containing protein 4 (ABHD4) to produce intermediate molecules, glycerophosphoacylethanolamides (GlyEth), and glycerophosphodiester phosphodiesterase 1 (GDE1). The synthetizing enzymes of 2-AG are phospholipase C-gamma-1 (PLCG1), phospholipase C-delta-1 (PLCD1), diacylglycerol lipase-alpha (DAGLA) and -beta (DAGLB). The degrading enzymes of AEA are fatty acid amide hydrolase (FAAH and FAAH2) and cytochrome P450 4X1 (CYP4X1). The degrading enzymes of 2-AG are Abhydrolase domain-containing protein 2 and 12 (ABHD2, and 12) and monoglyceride lipase (MAGL). The degradation of endocannabinoids induce the production of ARA and ethanolamine or glycerol