scholarly journals Aging attenuates the ovarian circadian rhythm

2020 ◽  
Author(s):  
Ziru Jiang ◽  
Kexin Zou ◽  
Xia Liu ◽  
Hangchao Gu ◽  
Yicong Meng ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Circadian Clock ◽  
Granulosa Cells ◽  
Clock Genes ◽  
University Hospital ◽  
Vitro Fertilization ◽  
Human Granulosa Cells ◽  
Circadian Clock Genes ◽  
Young Mice

Abstract Objective To study the effect of aging on ovarian circadian rhythm. Design Human and animal study. Setting University hospital and research laboratory. Patients/animals Human granulosa cells were obtained by follicular aspiration from women undergoing in vitro fertilization (IVF), and ovarian and liver tissues were obtained from female C57BL/6 mice. Intervention(s) None. Main outcome measure(s) Expression of circadian genes in young and older human granulosa cells and circadian rhythm in ovaries and livers of young and older mice. Result(s) All examined circadian clock genes in human granulosa cells showed a downward trend in expression with aging, and their mRNA expression levels were negatively correlated with age (P < 0.05). Older patients (≥ 40 years of age) had significantly reduced serum anti-Müllerian hormone (AMH) levels. Except for Rev-erbα, all other examined circadian clock genes were positively correlated with the level of AMH (P < 0.05). The circadian rhythm in the ovaries of older mice (8 months) was changed significantly relative to that in ovaries of young mice (12 weeks), although the circadian rhythm in the livers of older mice was basically consistent with that of young mice. Conclusion(s) Lower ovarian reserve in older women is partially due to ovarian circadian dysrhythmia as a result of aging.

scholarly journals Circadian Clock Genes REV-ERBs Inhibits Granulosa Cells Apoptosis by Regulating Mitochondrial Biogenesis and Autophagy in Polycystic Ovary Syndrome

2021 ◽  
Vol 9 ◽  
Author(s):  
Lihua Sun ◽  
Hui Tian ◽  
Songguo Xue ◽  
Hongjuan Ye ◽  
Xue Xue ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Circadian Clock ◽  
Granulosa Cells ◽  
Clock Genes ◽  
Polycystic Ovary ◽  
Follicular Development ◽  
Ovary Syndrome ◽  
Circadian Clock Genes ◽  
Mitochondrial Biosynthesis

Polycystic ovary syndrome (PCOS) is an endocrinopathy with complex pathophysiology that is a common cause of anovulatory infertility in women. Although the disruption of circadian rhythms is indicated in PCOS, the role of the clock in the etiology of these pathologies has yet to be appreciated. The nuclear receptors REV-ERBα and REV-ERBβ are core modulators of the circadian clock and participate in the regulation of a diverse set of biological functions. However, in PCOS, the expression of REV-ERBs and their effects remain unclear. Here, we demonstrate that the levels of REV-ERBα and REV-ERBβ expression were lower in the granulosa cells of PCOS patients than in control subjects. In vitro, we found that the overexpression of REV-ERBα and REV-ERBβ, and their agonist SR9009, promoted the expression of mitochondrial biosynthesis genes PGC-1α, NRF1, and TFAM and inhibited autophagy in KGN cells. Our results also indicate that REV-ERBα and REV-ERBβ can inhibit apoptosis in granulosa cells and promote proliferation. Importantly, the REV-ERB agonist SR9009 ameliorates abnormal follicular development by promoting mitochondrial biosynthesis and inhibiting autophagy in a mouse PCOS model. This allows us to speculate that SR9009 has potential as a therapeutic agent for the treatment of PCOS.

CORTISOL CIRCADIAN RHYTHM AND INSULIN RESISTANCE IN MUSCLE: EFFECT OF DOSING AND TIMING OF HYDROCORTISONE EXPOSURE ON INSULIN SENSITIVITY IN SYNCHRONIZED MUSCLE CELLS.

2020 ◽  
Author(s):  
Mariarosaria Negri ◽  
Claudia Pivonello ◽  
Chiara Simeoli ◽  
Gilda Di Gennaro ◽  
Mary Anna Venneri ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Circadian Rhythm ◽  
Insulin Sensitivity ◽  
Circadian Clock ◽  
Insulin Signaling ◽  
Clock Genes ◽  
Muscle Cells ◽  
C2c12 Cells ◽  
Circadian Expression

Introduction/Aim: Circadian rhythm disruption is emerging as a risk factor for metabolic disorders and particularly, alterations in clock genes circadian expression have been shown to influence insulin sensitivity. Recently, the reciprocal interplay between the circadian clock machinery and HPA axis has been largely demonstrated: the circadian clock may control the physiological circadian endogenous glucocorticoids secretion and action; glucocorticoids, in turn, are potent regulator of the circadian clock and their inappropriate replacement has been associated with metabolic impairment. The aim of the current study was to investigate in vitro the interaction between the timing-of-the-day exposure to different hydrocortisone (HC) concentrations on muscle insulin sensitivity. Methods: Serum-shock synchronized mouse skeletal muscle C2C12 cells were exposed to different HC concentrations recapitulating the circulating daily physiological cortisol profile (standard cortisol profile), the circulating daily cortisol profile that reached in adrenal insufficient (AI) patients treated with once-daily MR-HC (flat cortisol profile) and treated with thrice-daily of conventional IR-HC (steep cortisol profile). The 24 hrs spontaneous oscillation of the clock genes in synchronized C2C12 cells was used to align the timing for in vitro HC exposure (Bmal1 acrophase, midphase and bathyphase) with the reference times of cortisol peaks in AI treated with IR-HC (8 am, 1 pm, 6 pm). A panel of 84 insulin sensitivity related genes and intracellular insulin signaling proteins were analyzed by RT-qPCR and western blot, respectively. Results: Only the steep profile, characterized by a higher HC exposure during Bmal1 bathyphase, produced significant downregulation in 21 insulin sensitivity-related genes. Among these, Insr, Irs1, Irs2, Pi3kca and Adipor2 were downregulated when compared the flat to the standard or steep profile. Reduced intracellular IRS1 Tyr608, AKT Ser473, AMPK Thr172 and ACC Ser79 phosphorylations were also observed. Conclusions: The current study demonstrated that is late-in-the-day cortisol exposure that modulates insulin sensitivity-related genes expression and intracellular insulin signaling in skeletal muscle cells.

scholarly journals Stimulation of Apoptosis in Human Granulosa Cells from in Vitro Fertilization Patients and Its Prevention by Dexamethasone: Involvement of Cell Contact and Bcl-2 Expression

2002 ◽  
Vol 87 (7) ◽  
pp. 3441-3451 ◽  
Author(s):  
Ravid Sasson ◽  
Abraham Amsterdam
Keyword(s):  
In Vitro Fertilization ◽  
Actin Cytoskeleton ◽  
Gap Junctions ◽  
Granulosa Cells ◽  
Connexin 43 ◽  
Pronounced Increase ◽  
Vitro Fertilization ◽  
Human Granulosa Cells ◽  
Progesterone Production

Human granulosa cells obtained from in vitro fertilization patients are highly luteinized, but can still be stimulated by LH/cAMP for production of progesterone. This stimulation involved enhancement of apoptosis. Incubation of the cells with dexamethasone (Dex) reduced the apoptotic incidence compared with nontreated cells and completely abolished the increase in apoptosis stimulated by LH or forskolin, concomitantly with a pronounced increase in progesterone production. Organization of the actin cytoskeleton was dramatically reduced after LH/forskolin stimulation. In contrast, Dex prevented disorganization of the actin filament networks. LH and forskolin also decreased the organization of gap junctions, which could be prevented by Dex. However, the intracellular level of connexin 43 was elevated in the presence of LH, forskolin, and Dex. Endogenous levels of the survival gene protein Bcl-2 were significantly elevated in all cultures treated with Dex compared with either nonstimulated cultures or cultures stimulated with LH and forskolin. Our data suggest that LH/cAMP can stimulate steroidogenesis even during the initial stage of apoptosis of human granulosa cells, whereas Dex, which blocks apoptosis, could further elevate progesterone production. Moreover, the integrity of gap junctions and the actin cytoskeleton as well as elevated levels of Bcl-2 may play an important role in the suppression of apoptosis of human granulosa cells.

Modulatory effects of 5-fluorouracil on the rhythmic expression of circadian clock genes: A possible mechanism of chemotherapy-induced circadian rhythm disturbances

2008 ◽  
Vol 75 (8) ◽  
pp. 1616-1622 ◽  
Author(s):  
Hideyuki Terazono ◽  
Ahmed Hamdan ◽  
Naoya Matsunaga ◽  
Naoto Hayasaka ◽  
Hiroaki Kaji ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Circadian Clock ◽  
Clock Genes ◽  
Rhythmic Expression ◽  
Circadian Clock Genes

Effect of noradrenaline and dopamine on progesterone and estradiol secretion of human granulosa cells

1993 ◽  
Vol 129 (2) ◽  
pp. 165-168 ◽  
Author(s):  
József Bódis ◽  
Hans R Tinneberg ◽  
Attila Török ◽  
Philippe Cledon ◽  
Volker Hanf ◽  
...  
Keyword(s):  
Granulosa Cells ◽  
Direct Action ◽  
Serum Free Medium ◽  
Free Medium ◽  
Vitro Fertilization ◽  
Serum Free ◽  
Human Granulosa Cells ◽  
Estradiol Secretion ◽  
Cells Cultured

The aim of this study was to explore the direct action of noradrenaline and dopamine on progesterone and estradiol secretion of human granulosa cells cultured in serum-free medium. Progesterone and estradiol production was measured in the presence and absence of noradrenaline, dopamine or propranolol using radioimmunoassays; statistical analysis was performed by analysis of variance and Newman-Keul's multiple range test. Twenty-six women aged 31±3 years undergoing in vitro fertilization and embryo transfer for infertility treatment at University Women's Hospital, University of Tübingen, Germany, took part in this study. Noradrenaline significantly inhibited progesterone production by human granulosa cells in a dose-related manner at a concentration of 10−4–10−6 mol/l. Dopamine significantly stimulated estradiol secretion by granulosa cells in an inverse dose-related manner. Both effects were blocked by propranolol. The results suggest that catecholaminergic actions switch over the steroid production of human granulosa cells cultured in serum-free medium from progesterone to estradiol.

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