Synergistic effect between LH and estrogen in the acceleration of cumulus expansion via GPR30 and EGFR pathways

Abstract

The estrogen membrane receptor GPR30 (also known as G-protein coupled receptor 30) has recently been shown to be involved in the regulation of oocyte maturation and cumulus expansion. However, whether GPR30 expression is regulated by gonadotropin stimulation and how it participates in the regulation of the maturation process is still not clear. In this study, we explored the mechanism underlying the synergy between luteinizing hormone and 17β-estradiol (17β-E 2 ) to improve the epidermal growth factor (EGF) response in cumulus oocyte complexes (COCs) during oocyte maturation in mice. The expression and distribution of GPR30, EGFR, and EGF-like growth factors were examined by real-time quantitative PCR, western blot, and immunofluorescence staining. Lyso-Tracker Red labeling was performed to detect the lysosomal activity in follicle granular cells (FGCs). Cumulus expansion of COCs was evaluated after in vitro maturation for 16 h. We found that EGF-like growth factors transmit LH signals to increase GRP30 levels by inhibiting protein degradation in lysosomes. Meanwhile, 17β-E 2 stimulates the GPR30 signaling pathway to increase EGF receptor levels, enhancing the response ability of EGF signaling in COCs and thus promoting cumulus expansion. In conclusion, our study reveals the synergistic mechanism between LH and estrogen in the regulation of cumulus expansion during oocyte maturation process.

Chlorinated Polycyclic Aromatic Hydrocarbons Induce Immunosuppression in THP-1 Macrophages Characterized by Disrupted Amino Acid Metabolism

“…Fluorescence images (20× water objective, 19 fields per well) were collected by Operetta and analyzed by Harmony. The relative fluorescence intensity in the treated group to that of the DMSO group is described as the lysosomal activity …”

“…The relative fluorescence intensity in the treated group to that of the DMSO group is described as the lysosomal activity. 29 2. unsupervised analysis according to the ClusterProfiler R package (R 4.1.2, https://www.r-project.org/). Functional enrichment GO analysis was conducted using the STRING database (version 11.5).…”

Role of EGFR expressed on the granulosa cells in the pathogenesis of polycystic ovarian syndrome

“…LH released by the anterior pituitary binds to its receptor LHCGR, expressed on the surface of granulosa cells at the time of ovulation, and stimulates the release of EGF-like peptides from the ovarian somatic cells (31). LHCGR is expressed on the granulosa cells while the oocyte and the cumulus granulosa cells are not directly responsive to LH, thus, the EGF/EGFR pathway plays a vital role in mediating the communication between LH and the oocyte (32). Granulosa cells provide the physical support for developing oocyte and actively differentiated with distinct populations during folliculogenesis (33).…”

Melatonin Alleviates the Suppressive Effect of Hypoxanthine on Oocyte Nuclear Maturation and Restores Meiosis via the Melatonin Receptor 1 (MT1)-Mediated Pathway

“…Another important aspect observed in the study is the potential association of melatonin and MT1 with LH. LH plays a pivotal role in oocyte maturation ( Fan et al, 2008 ; Zamah et al, 2010 ; Arroyo et al, 2020 ; Chen et al, 2020 ; Liu et al, 2020 ). LH is similar to melatonin, which can lower the concentration of cAMP within the oocyte but has different mechanisms than melatonin ( Sethi et al, 2008 ; Muhlbauer et al, 2011 ; Lyga et al, 2016 ).…”