A mouse model reveals the events and underlying regulatory signals during the gonadotrophin-dependent phase of follicle development

Abstract

During folliculogenesis, the gonadotrophin-dependent phase begins at the small antral follicle stage and ends with Graafian follicles. In this study, pregnant mare’s serum gonadotrophin was used to induce gonadotrophin-dependent folliculogenesis in mice, following which the developmental events that follicles undergo, as well as the underlying regulatory signals, were investigated at both the morphological and transcriptomic level. Gonadotrophin-dependent folliculogenesis consisted of three phases: preparation, rapid growth, and decelerated growth. In the preparation phase, comprising the first 12 h, granulosa cells completed the preparations for proliferation and differentiation, shifted energy metabolism to glycolysis, and reduced protein synthesis and processing. The rapid growth phase lasted from 12 to 24 h; in this phase, granulosa cells completed their proliferation, and follicles acquired the capacity for estradiol secretion and ovulation. Meanwhile, the decelerating growth phase occurred between 24 and 48 h of gonadotrophin-dependent folliculogenesis. In this phase, the proliferation and expansion of the follicular antrum were reduced, energy metabolism was shifted to oxidative phosphorylation, and cell migration and lipid metabolism were enhanced in preparation for luteinization. We also revealed the key signaling pathways that regulate gonadotrophin-dependent folliculogenesis and elucidated the activation sequence of these pathways. A comparison of our RNA-sequencing data with that reported for humans suggested that the mechanisms involved in mouse and human folliculogenesis are evolutionarily conserved. In this study, we draw a detailed atlas of gonadotrophin-dependent folliculogenesis, thereby laying the foundation for further investigation of the regulatory mechanisms underlying this process.

Luzindole and 4P-PDOT block the effect of melatonin on bovine granulosa cell apoptosis and cell cycle depending on its concentration

“…Granulosa cells apoptosis or survival is considered as a signal for follicle development and oocyte growth, thus granulosa cells are essential for cell proliferation, follicular development, oocyte maturation, follicle ultimately ovulates or undergoes atresia ( Matsuda et al, 2012 ; Choi et al, 2011 ; Tanabe et al, 2015 ; Kadariya et al, 2015 ; Chen et al, 2020 ). Even the granulosa cells state could determine the fate of follicle, mainly due to its effect on synthesize of steroids, growth factors, and cytokines, which have been proved to be essential for oocytes mature and follicle development ( Matsuda et al, 2012 ; M’baye et al, 2015 ; Wang et al, 2017a , 2018 ; Chen et al, 2020 ). Therefore, improving the granulosa cells functions become very important for acting its physiological role during oocytes mature and follicle development.…”

“…The luteinization of granulosa cells is essential for pregnancy maintenance, which is a temporary organ for secretion of progesterone ( He et al, 2016a ). During follicles development, granulosa cells completed the preparations for proliferation and differentiation, shifted energy metabolism to glycolysis, and follicles acquired the capacity for estradiol secretion and ovulation ( Chen et al, 2020 ). The granulosa cells within the follicle accompanied by the proliferation, differentiation, and apoptosis during the reproductive period ( Chowdhury et al, 2016 ; Denkova et al, 2014 ; Chen et al, 2020 ).…”

“…During follicles development, granulosa cells completed the preparations for proliferation and differentiation, shifted energy metabolism to glycolysis, and follicles acquired the capacity for estradiol secretion and ovulation ( Chen et al, 2020 ). The granulosa cells within the follicle accompanied by the proliferation, differentiation, and apoptosis during the reproductive period ( Chowdhury et al, 2016 ; Denkova et al, 2014 ; Chen et al, 2020 ). Therefore, the apoptosis cause the change of granulosa cells function and disturb the state of follicle development.…”

A Prepubertal Mice Model to Study the Growth Pattern of Early Ovarian Follicles

“…Fshr and Lhcgr act as antennas on the follicle, where they are responsible for receiving gonadotropin signals from the pituitary gland [ 29 , 30 , 31 ]. In the current study, we found that both Fshr and Lhcgr were gradually upregulated at the early stage of folliculogenesis; soon afterwards, they underwent a period of rapid increase and then reached a plateau.…”

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).…”