The role of sex steroid hormones, cytokines and the endocannabinoid system in female fertility

Karasu, Tülay; Marczylo, Timothy H.; Maccarrone, Mauro; Konje, J. C.

doi:10.1093/humupd/dmq058

Cited by 91 publications

(80 citation statements)

References 179 publications

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“…Furthermore, because ECs and ERCs were involved in behavioral regulation of feeding ( 38 ) as well as in psychiatric disorders ( 39,40 ), we purposely excluded from recruitment subjects with eating disorders such as anorexia nervosa and binge-eating disorders ( 41 ) or subjects showing symptoms of anxiety and depression ( 42 ), according to the results of psychometric tests. Moreover, as ECs and ERCs were involved in fertility and in sleep regulation, we included only subjects who reported a regular wake-sleep cycle and females with a regular menstrual cycle ( 43,44 ).…”

Section: Discussionmentioning

confidence: 99%

Estimation of reference intervals of five endocannabinoids and endocannabinoid related compounds in human plasma by two dimensional-LC/MS/MS

Fanelli

Lallo

Belluomo

et al. 2012

Journal of Lipid Research

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Supplementary key words endocannabinoids • validation • reference intervalsThe endocannabinoids (ECs) are bioactive lipid mediators derived from membrane phospholipids. Since the discovery of the fi rst lipid mediator of the endocannabinoid system (ECS), arachidonoyl-ethanolamide (AEA), also called anandamide ( 1 ), several molecules belonging to this family were identifi ed, the most important being 2-arachidonoyl-glycerol (2AG) and its isomer 1AG among MAGs ( 2, 3 ), palmitoyl-ethanolamide (PEA) and oleoylethanolamide (OEA) among the NAEs, to which AEA belongs ( 4 ). Both 2AG and AEA act on cannabinoid receptor type 1 (CB1) and type 2 (CB2), whereas PEA and OEA act by infl uencing AEA metabolism and binding the peroxisome proliferator-activated receptor ␣ ( 5, 6 ), thus defi ned endocannabinoid related compounds (ERC ).Abstract The elucidation of the role of endocannabinoids in physiological and pathological conditions and the transferability of the importance of these mediators from basic evidence into clinical practice is still hampered by the indefi niteness of their circulating reference intervals. In this work, we developed and validated a two-dimensional LC/ MS/MS method for the simultaneous measurement of plasma endocannabinoids and related compounds such as arachidonoyl-ethanolamide, palmitoyl-ethanolamide, and oleoylethanolamide, belonging to the N-acyl-ethanolamide (NAE) family, and 2-arachidonoyl-glycerol and its inactive isomer 1-arachidonoyl-glycerol from the monoacyl-glycerol (MAG) family. We found that several pitfalls in the endocannabinoid measurement may occur, from blood withdrawal to plasma processing. Plasma extraction with toluene followed by online purifi cation was chosen, allowing high-throughput and reliability. We estimated gender-specifi c reference intervals on 121 healthy normal weight subjects fulfi lling rigorous anthropometric and hematic criteria. We observed no gender differences for NAEs, whereas signifi cantly higher MAG levels were found in males compared with females. MAGs also signifi cantly correlated with triglycerides. NAEs increased with age in females, and arachidonoyl-ethanolamide correlated with adiposity and metabolic parameters in females. This work paves the way to the establishment of defi nitive reference intervals for circulating endocannabinoids to help physicians move from the speculative research fi eld into the clinical fi eld. -Fanelli,F

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Section: Discussionmentioning

confidence: 99%

Estimation of reference intervals of five endocannabinoids and endocannabinoid related compounds in human plasma by two dimensional-LC/MS/MS

Fanelli

Lallo

Belluomo

et al. 2012

Journal of Lipid Research

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“…The ECS interacts with sex steroid hormones and cytokines, thus indirectly regulating fertility (421). CB1 and CB2 are expressed in preimplantation mouse embryos (902).…”

Section: Reproductive Systemmentioning

confidence: 99%

From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology

Ligresti¹,

Petrocellis²,

Marzo³

2016

Physiological Reviews

365

337

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Apart from having been used and misused for at least four millennia for, among others, recreational and medicinal purposes, the cannabis plant and its most peculiar chemical components, the plant cannabinoids (phytocannabinoids), have the merit to have led humanity to discover one of the most intriguing and pleiotropic endogenous signaling systems, the endocannabinoid system (ECS). This review article aims to describe and critically discuss, in the most comprehensive possible manner, the multifaceted aspects of 1) the pharmacology and potential impact on mammalian physiology of all major phytocannabinoids, and not only of the most famous one ⌬ 9 -tetrahydrocannabinol, and 2) the adaptive prohomeostatic physiological, or maladaptive pathological, roles of the ECS in mammalian cells, tissues, and organs. In doing so, we have respected the chronological order of the milestones of the millennial route from medicinal/recreational cannabis to the ECS and beyond, as it is now clear that some of the early steps in this long path, which were originally neglected, are becoming important again. The emerging picture is rather complex, but still supports the belief that more important discoveries on human physiology, and new therapies, might come in the future from new knowledge in this field.

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“…Embryo implantation is established and maintained by a network of complex molecules that are involved in physiological changes of the endometrium, including hormones, cytokines, growth factors, and their interactions [1]. It can only occur over a restricted period after ovulation called "implantation window" lasting about 24 h in mouse spanning early on day 4 to middle of the day 5 of pregnancy.…”

Section: Introductionmentioning

confidence: 99%

Identification of stathmin 1 during peri-implantation period in mouse endometrium by a proteomics-based analysis

Gou

Jia

Zhao

et al. 2015

Biochemical and Biophysical Research Communications

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The role of sex steroid hormones, cytokines and the endocannabinoid system in female fertility

Cited by 91 publications

References 179 publications

Estimation of reference intervals of five endocannabinoids and endocannabinoid related compounds in human plasma by two dimensional-LC/MS/MS

Estimation of reference intervals of five endocannabinoids and endocannabinoid related compounds in human plasma by two dimensional-LC/MS/MS

From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology

Identification of stathmin 1 during peri-implantation period in mouse endometrium by a proteomics-based analysis

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