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Review
. 2019 Jan 15;12(1):3.
doi: 10.1186/s13048-018-0478-9.

The role of the endocannabinoid system in female reproductive tissues

O'Llenecia S Walker  1 , Alison C Holloway  2 , Sandeep Raha  3
Affiliations
Review

The role of the endocannabinoid system in female reproductive tissues

O'Llenecia S Walker et al. J Ovarian Res. .

Abstract

There has been increasing interest in the role of endocannabinoids as critical modulators of the female reproductive processes. Endocannabinoids are natural ligands of cannabinoid, vanilloid, and peroxisome proliferator-activated receptors. Together with their receptors, enzymes and downstream signaling targets, they form the endocannabinoid system (ECS). While the ECS is known to modulate pain and neurodevelopment, it is also known to impact the female reproductive system where it affects folliculogenesis, oocyte maturation, and ovarian endocrine secretion. In addition, the ECS affects oviductal embryo transport, implantation, uterine decidualization and placentation. There is a complex interplay between the ECS and the hypothalamic-pituitary-ovarian axis, and an intricate crosstalk between the ECS and steroid hormone production and secretion. Exogenous cannabinoids, derived from plants such as Cannabis sativa, are also ligands for cannabinoid receptors. These have been shown to have clinical outcomes related to ECS dysregulation, including multiple sclerosis, Alzheimer's disease, and amyotrophic lateral sclerosis, along with adverse effects on female reproduction. The aim of this review is to describe and discuss data from human, animal, and in vitro studies that support the important role of the endocannabinoid system in female reproductive tissues and processes. In particular, we will discuss some of the mechanisms by which endocannabinoid signaling can affect ovarian function in both physiological and pathophysiological states.

Keywords: Cannabis; Endocannabinoid system; Female reproduction; Ovarian cancer; Ovary; PCOS.

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The authors declare that they have no competing interests.

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Figures

Fig. 1
Fig. 1
Summary of the major effects of the ECS on the HPO axis. High levels of endocannabinoids and exogenous cannabinoids suppress the release of gonadotropin releasing hormone (GnRH), luteinizing hormone (LH), follicle stimulating hormone (FSH), estrogen and progesterone. Mitochondrial function is associated with oocyte quality. The presence of CB1 on the outer mitochondrial membrane may perturb ovarian function and subsequently oogenesis. Black boxes indicate components of the ECS that have been identified within the anatomical structures represented by each of the blue boxes. Yellow ovals indicate hormones released along the HPO axis when unperturbed. When each of the anatomical structures are perturbed by cannabinoids, the release of the hormones in the yellow ovals is prevented
Fig. 2
Fig. 2
Proposed involvement of the ECS in the pathogenesis of PCOS. The main pathogenic factors relating to PCOS and the influence of some ECS components are illustrated. Black boxes indicate components of the ECS; green boxes indicate metabolic components; orange boxes indicate endocrine/reproductive components
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