Dynamics of expression and localization of the cannabinoid system in granulosa cells during oocyte nuclear maturation

Agirregoitia, Ekaitz; Ibarra-Lecue, Inés; Totorikaguena, Lide; Mendoza, Rosario; Expósito, Antonia; Matorras, Roberto; Urigüen, Leyre; Agirregoitia, Naiara

doi:10.1016/j.fertnstert.2015.06.013

Cited by 22 publications

(20 citation statements)

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“…1 D, E ). As the functional unit for in vitro maturation (IVM) is the COC, we also observed that CB 1 and CB 2 appeared in the granulosa cells enveloping the mouse oocyte (data not shown), as recently described in humans (4). The specificity of the antibodies was validated using the specific blocking peptides as well as the use of oocytes from CB 1 ‐ and CB 2 ‐KO mice (Fig.…”

Section: Resultssupporting

confidence: 81%

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CB₁cannabinoid receptor drives oocyte maturation and embryo development via PI3K/Akt and MAPK pathways

et al. 2017

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Endocannabinoids have been recognized as mediators of practically all reproductive events in mammals. However, little is known about the role of this system in oocyte maturation. In a mouse model, we observed that activation of cannabinoid receptor 1 (CB) during oocyte maturation modulated the phosphorylation status of Akt and ERK1/2 and enhanced the subsequent embryo production. In the absence of CB, oocyte maturation was impaired and embryo development delayed. Cannabinoid receptor 2 (CB) was unable to rescue these effects. Finally, we confirmed abnormal oocyte maturation rather than impaired embryonic transport through the oviduct in CB knockouts. Our data suggest that cannabinoid agonists may be useful maturation supplements. For fertilization patients intolerant to gonadotropins, this could be a promising and only option.-López-Cardona, A. P., Pérez-Cerezales, S., Fernández-González, R., Laguna-Barraza, R., Pericuesta, E., Agirregoitia, N., Gutiérrez-Adán, A., Agirregoitia, E. CB cannabinoid receptor drives oocyte maturation and embryo development PI3K/Akt and MAPK pathways.

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Section: Resultssupporting

confidence: 81%

“…Components of the endocannabinoid system have been identified in human (2)(3)(4)(5), and rat (6) follicles. The cannabinoid receptors 1 (CNR1, also called CB 1 ) and 2 (CNR2, also called CB 2 ) are GPCR-Gais that mainly inhibit adenylyl cyclase, reducing cyclic AMP and blocking PKA.…”

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confidence: 99%

CB₁cannabinoid receptor drives oocyte maturation and embryo development via PI3K/Akt and MAPK pathways

et al. 2017

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“…In particular, several studies revealed that CNR1 and CNR2 receptors are expressed, in a manner that is dependent on the follicle maturation stage, by oocytes, granulosa cells of primordial, primary, secondary, tertiary follicles, corpus luteum and corpus albicans [ 28 , 30 ]; the same researchers also investigated the enzymatic machinery for the regulation of AEA tone, highlighting that NAPE-PLD was expressed in granulosa and theca cells of secondary and tertiary follicles and in corpus luteum and corpus albicans, while FAAH was present in the same follicular developmental stages, but only in theca cells [ 30 ]. A more recent study analysed the dynamic expression of CNR1 , CNR2 , FAAH and MAGL in granulosa cells retrieved from oocytes at GV, MI and MII stages, suggesting a role of the endocannabinoid system in regulating the nuclear maturation of the oocyte [ 31 ]. In addition, studies focusing on AEA plasma concentrations during the menstrual cycle evidenced that the highest AEA levels corresponded to ovulation, while the lowest level corresponded to the late luteal phase [ 32 ].…”

Section: Introductionmentioning

confidence: 99%

The Impact of Controlled Ovarian Stimulation Hormones on the Metabolic State and Endocannabinoid System of Human Cumulus Cells

Notarstefano

Gioacchini

Giorgini

et al. 2020

IJMS

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Different Follicle Stimulating Hormone (FSH) formulation and Luteinizing Hormone (LH) are used in Assisted Reproductive Technology (ART) to induce follicles development and oocytes maturation, but it is still under debate which protocol is to be preferred. In the present study, the different effects on cumulus cells (CCs) of three controlled ovarian stimulation (COS) protocols, based on urinary FSH, recombinant FSH, or human Menopausal Gonadotropin (hMG) administration, were assessed. CCs were obtained from 42 normal-responders women undergoing COS, randomly divided into three groups according to the used gonadotropin formulation. Differences were found in the expression of genes belonging to the endocannabinoid system (the receptors CNR1, CNR2 and TRPV1, and the enzymes involved in the metabolisms of anandamide, NAPE-PLD and FAAH, and 2-acylglycerol, DAGL and MAGL); consistently, changes in lipid (PPARα, and FASN) and carbohydrate (GLUT1 and GLUT9) metabolisms, in CCs’ macromolecules composition (highlighted by Fourier Transform Infrared Microspectroscopy, FTIRM), and in the number of retrieved oocytes were found. For the first time, statistically significant evidence on the differences related to each COS protocol on the endocannabinoid system, metabolism and macromolecular composition of CCs was found, representing a proof of concept to be further confirmed in a larger cohort of patients.

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“…More interesting still is our study in which we detected CB1 and FAAH in granulosa cells from GV to MII oocytes and their co-localization in some portions of the cell membrane. Moreover, MGLL immunostaining was more homogeneous across the cell and only overlapped with CB1 weakly (Agirregoitia et al 2015).…”

Section: Discussionmentioning

confidence: 95%

“…To date, the presence of 2-AG has only been described in the uterus of the female reproductive tract (Wang et al 2007) but whether it is present in the ovary or the oviduct is unknown; this merits investigation to elucidate the role of MGLL during the resumption of meiosis. In addition, the presence of CB1, FAAH and M G L L i n g r a n u l o s a c e l l s s u g g e s t s t h a t t h e endocannabinoids act not only over the oocyte but also over the granulosa cells (Agirregoitia et al 2015).…”

Section: Discussionmentioning

confidence: 99%

Dynamic of expression and localization of cannabinoid-degrading enzymes FAAH and MGLL in relation to CB1 during meiotic maturation of human oocytes

et al. 2016

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The endogenous cannabinoid system has been characterized in some female reproductive organs but little is known about the expression and localization pattern of cannabinoid-degrading enzymes in relation to the CB1 cannabinoid receptor in human oocytes. In this study, we focus on the investigation of the presence and differential distribution of fatty acid amide hydrolase (FAAH) and monoglyceride lipase (MGLL) in relation to CB1 during the maturation of human oocytes. We used a total of 290 human oocytes not suitable for in vitro fertilization/intracytoplasmic sperm injection (ICSI): germinal-vesicle (GV) and metaphase-I (MI) stages and metaphase-II (MII) oocytes that had not developed into an embryo after ICSI. Cannabinoid-degrading enzymes and the cannabinoid CB1 receptor were present in human oocytes. Specifically, FAAH was detected in the periphery of the oocyte from the GV to MI stage and co-localized with CB1. Later, by the MII stage, FAAH was spread within the oocyte, whereas MGLL immunostaining was homogeneous across the oocyte at all stages of maturation and only overlapped with CB1 at the GV stage. This coordinated redistribution of cannabinoid system proteins suggests a role for this system in the maturation of the female gamete.

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Dynamics of expression and localization of the cannabinoid system in granulosa cells during oocyte nuclear maturation

Cited by 22 publications

References 40 publications

CB₁cannabinoid receptor drives oocyte maturation and embryo development via PI3K/Akt and MAPK pathways

CB₁cannabinoid receptor drives oocyte maturation and embryo development via PI3K/Akt and MAPK pathways

The Impact of Controlled Ovarian Stimulation Hormones on the Metabolic State and Endocannabinoid System of Human Cumulus Cells

Dynamic of expression and localization of cannabinoid-degrading enzymes FAAH and MGLL in relation to CB1 during meiotic maturation of human oocytes

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Dynamics of expression and localization of the cannabinoid system in granulosa cells during oocyte nuclear maturation

Cited by 22 publications

References 40 publications

CB1cannabinoid receptor drives oocyte maturation and embryo development via PI3K/Akt and MAPK pathways

CB1cannabinoid receptor drives oocyte maturation and embryo development via PI3K/Akt and MAPK pathways

The Impact of Controlled Ovarian Stimulation Hormones on the Metabolic State and Endocannabinoid System of Human Cumulus Cells

Dynamic of expression and localization of cannabinoid-degrading enzymes FAAH and MGLL in relation to CB1 during meiotic maturation of human oocytes

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CB₁cannabinoid receptor drives oocyte maturation and embryo development via PI3K/Akt and MAPK pathways

CB₁cannabinoid receptor drives oocyte maturation and embryo development via PI3K/Akt and MAPK pathways