Immunolocalization for glucocorticoid receptor and effect of cortisol on in vitro development of preantral follicles

Abstract

Highlights In this study, the immunolocalization for glucocorticoid receptor (NR3C1) in goat ovarian follicles and the effect of cortisol on in vitro development of preantral follicles was evaluate. The NR3C1 was strongly expressed in oocytes of primary and antral follicles. A progressive increase of immunostaining for NR3C1 in granulosa cells from primordial to antral follicles was observed. In conclusion, it was observed the presence of NR3C1 in the oocyte and granulosa cells in all follicular categories. The in vitro culture showed that high cortisol concentration (10 ng/ml) exerts a deleterious effect on follicular survival.

Glucocorticoids, Stress and Delta-9 Tetrahydrocannabinol (THC) during Early Embryonic Development

“…Taken together, data collected from Ravisankar et al (2021), evidenced that glucocorticoids may play an important role during COC expansion by binding NR3C1, and that the ratio of cortisol to cortisone in follicular fluid was an accurate indicator of oocyte competence in primates [50]. These findings contradict Pontes et al (2019) who suggested that elevated cortisol concentrations were associated with a reduction in the diameter and quality of both oocytes and follicles in goats. It is possible that such discrepancies may be a result of species differences in the regulation of cortisol in pre-ovulatory follicles.…”

“…Although THC may result in a temporary inhibition of psychoactive stress [ 10 ], the literature presents discrepancies regarding the effects of THC on molecular stress signaling in reproductive organs and tissues. There is evidence to suggest that both stress signaling via circulating glucocorticoids, along with THC, have significant impact on reproductive development parameters such as oocyte maturation, quality, competence, and blastocyst rates [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. However, there is a lack of research that explores the potential interactions between signaling pathways activated by THC and stress hormones at the level of the oocyte and embryo during early development.…”

“…The impact of glucocorticoids on their target organs is primarily modulated by the local number of glucocorticoid receptors (GRs) and the concentration of active hormone available to bind to the GRs ( Table 1 ) [ 22 , 48 , 49 ]. NR3C1 is one of the main GR subtypes that has been shown to be expressed in the ovaries of many different mammalian species [ 17 , 20 , 21 , 22 , 50 , 51 , 52 ] and is part of the nuclear receptor subfamily ligand-dependent transcription factors [ 50 ]. NR3C1 forms a receptor complex upon binding to cortisol, which translocates from the cytoplasm to the nucleus and binds to glucocorticoid response elements (GREs) on DNA to alter transcription and downstream gene expression ( Figure 1 ) [ 17 , 50 , 52 , 53 ].…”

“…NR3C1 is one of the main GR subtypes that has been shown to be expressed in the ovaries of many different mammalian species [ 17 , 20 , 21 , 22 , 50 , 51 , 52 ] and is part of the nuclear receptor subfamily ligand-dependent transcription factors [ 50 ]. NR3C1 forms a receptor complex upon binding to cortisol, which translocates from the cytoplasm to the nucleus and binds to glucocorticoid response elements (GREs) on DNA to alter transcription and downstream gene expression ( Figure 1 ) [ 17 , 50 , 52 , 53 ]. Two main enzymes, 11b-hydroxysteroid dehydrogenase type 1 (HSD11B1) and type 2 (HSD11B2), are responsible for controlling the concentration of active glucocorticoids within target organs [ 21 , 22 ].…”

“…HSD11B1 is responsible for reducing inactive cortisone into active cortisol, while HSD11B2 is a dehydrogenase that oxidizes active cortisol to inactive cortisone [ 21 , 22 ]. Across various mammalian species, HSD11s and GRs have been shown to be expressed and regulate the hormonal microenvironment in many of the same cells and tissues as the ECS, including GCs, CCs, oocytes, embryos, follicular fluid, ovary, and placenta [ 17 , 21 , 22 , 49 , 50 , 52 , 54 ]. The hormonal microenvironment is tightly regulated throughout oocyte maturation, given that oocyte competence, quality, and capacity to produce an embryo can be altered by disruption to such processes [ 20 , 21 , 22 ].…”