scholarly journals Leptin Receptor Mediates Bmal1 Regulation of Estrogen Synthesis in Granulosa Cells

Animals ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 899 ◽  
Author(s):  
Chu ◽  
Ma ◽  
Sun ◽  
Zhu ◽  
Xiang ◽  
...  

Chronobiology affects female fertility in mammals. Lepr is required for leptin regulation of female reproduction. The presence of E-box elements in the Lepr promoter that are recognized and bound by clock genes to initiate gene transcription suggested that circadian systems might regulate fertility through Lepr. However, it is unclear whether Bmal1, a key oscillator controlling other clock genes, is involved in leptin regulation in hormone synthesis through Lepr. In this study, serum estradiol (E2) concentration and the expressions of Bmal1, Lepr, Cyp19a1, and Cyp11a1 genes were found to display well-synchronized circadian rhythms. Knockdown of Bmal1 significantly reduced expression levels of Lepr, Fshr, and Cyp19a1 genes; protein production of Bmal1, Lepr, and Cyp19a1; and the E2 concentration in granulosa cells. Knockdown of Lepr reduced the expression levels of Cyp19a1 and Cyp11a1 genes and Cyp19a1 protein, and also reduced E2 concentration. Addition of leptin affected the expression of Cyp19a1, Cyp11a1, and Fshr genes. Bmal1 deficiency counteracted leptin-stimulated upregulation of the genes encoding E2 synthesis in granulosa cells. These results demonstrated that Bmal1 participates in the process by which leptin acts on Lepr to regulate E2 synthesis.

1976 ◽  
Vol 54 (7) ◽  
pp. 1128-1139 ◽  
Author(s):  
Y. Nagahama ◽  
K. Chan ◽  
W. S. Hoar

Pre- and post-ovulatory follicles in the goldfish ovary were investigated histochemically and ultrastructurally. Special cells in the thecal layer of preovulatory follicles of yolk-laden oocytes showed 3β-hydroxy-Δ5-steroid dehydrogenase (3β-HSD; EC 1.1.1.145) activity typical of steroid hormone synthesis. Ultrastructurally, these thecal cells possess organelles characteristic of steroid-producing cells: mitochondria with tubular cristae and agranular endoplasmic reticulum. Unlike thecal ceils, the granulosa cells contain organelles typical of protein-secreting cells. These findings strongly suggest that only the special theca cells are sites of estrogen synthesis in the goldfish ovary.Postovulatory follicles, 6–10 h after ovulation, were characterized by a highly vascular thecal layer and hypertrophied granulosa cells. A weak but definite 3β-HSD activity occurs in both special theca cells and granulosa cells. Ultrastructurally, the granulosa cells contain many lipid droplets and numerous Golgi elements, suggesting the possible immediate transformation of granulosa cells to lutein cells during the ovulation. However, 30 h after ovulation, both granulosa cells and special theca cells showed advanced degenerative features and these data do not seem to support the hypothesis of an endocrine role for the older postovulatory follicles of the goldfish.


2021 ◽  
Vol 165 ◽  
pp. 92-98
Author(s):  
Lu Zhu ◽  
Jing Jing ◽  
Shuaiqi Qin ◽  
Qi Zheng ◽  
Jiani Lu ◽  
...  

2018 ◽  
Vol 11 (1) ◽  
Author(s):  
Amnon Brzezinski ◽  
A. Saada ◽  
H. Miller ◽  
NA Brzezinski-Sinai ◽  
A. Ben-Meir

2021 ◽  
Author(s):  
Jozsef Bodis ◽  
Endre Sulyok ◽  
Akos Varnagy ◽  
Viktória Prémusz ◽  
Krisztina Godony ◽  
...  

Abstract BackgroundThis observational clinical study evaluated the expression levels and predictive values of some apoptosis-related genes in granulosa cells (GCs) and follicular fluid (FF) of women undergoing in vitro fertilization (IVF).Methods GCs and FF were obtained at oocyte retrieval from 31 consecutive patients with heterogeneous infertility diagnosis (age: 34.3±5.8 years, body mass index: 24.02±3.12 kg/m2, duration of infertility: 4.2±2.1 years). mRNA expression of pro-apoptotic (BAX, CASP3, CASP8) and anti-apoptotic (BCL2, AMH, AMHR, FSHR, LHR, CYP19A1) factors was determined by quantitative RT-PCR using ROCHE LightCycler 480. Results No significant difference in GC or FF mRNA expression of pro- and anti-apoptotic factors could be demonstrated between IVF patients with (9 patients) or without (22 patients) clinical pregnancy. Each transcript investigated was detected in FF, but their levels were markedly reduced and independent of those in GCs. The number of retrieved oocytes was positively associated with GC AMHR (r=0.393, p=0.029), but the day of embryo transfer was negatively associated with GC LHR (r=-0.414, p=0.020) and GC FSHR transcripts (r=-0.535, p=0.002). When pregnancy positive group was analysed separately the impact of apoptosis- related gene expressions on some selected measures of IVF success could be observed. Strong positive relationship was found between gene expression levels of pro- and anti-apoptotic factors in GCs.ConclusionOur study provides only marginal evidences for the apoptosis dependence of IVF outcome and suggests that the apoptosis process induces adaptive increases of the anti-apoptotic gene expression to attenuate apoptosis and to protect cell survival.


2021 ◽  
Author(s):  
Qianzhun Huang ◽  
Xiaoyang Su ◽  
Ning Fang ◽  
Jian Huang

Abstract Background: Dysregulated circadian dynamic balance is strongly associated with cancer development. However, biological functions of circadian rhythms in lung adenocarcinoma (LUAD) have not been elucidated. This study aimed at valuating the modulatory effects of circadian rhythms in the LUAD tumor microenvironment.Methods: Multiple open-source bioinformatics research platforms are used to comprehensively elucidate the expression level, prognosis, potential biological function, drug sensitivity, and immune microenvironment of circadian clock genes in LUAD.Results: Most circadian clock genes in LUAD are dysregulated and are strongly correlated with patient prognosis, and missense mutations at splicing sites of these genes. Besides, these genes are closely associated with some well-known cancer-related marker pathways, which are mainly involved in the inhibition of the Apoptosis, Cell cycle, and DNA Damage Response Pathway. Furthermore, functional enrichment analysis revealedthat circadian clock genes regulate transcription factor activities and circadian rhythms in LUAD tissues. As for drug sensitivity, high expression of CLOCK, CRY1, and NR1D2 as well as suppressedPER2 and CRY2 expression levels are associated with drug resistance. The expression levels of circadian clock genes in LUAD correlate with immune infiltration and are involved in the regulation of immunosuppression.Conclusions: Our multi-omics analysis provides a more comprehensive understanding of the molecular mechanisms of the circadian clock genes in LUAD and provides new insights for a more precise screening of prognostic biomarkers and immunotherapy.


2021 ◽  
Author(s):  
Kaixuan Sun ◽  
Yinling Xiu ◽  
Jianbo Song ◽  
Yuexin Yu

Abstract ObjectiveThis study aims to investigate the expression of long noncoding RNA CTBP1-AS in patients with polycystic ovarian syndrome (PCOS) and its effects on the proliferation and autophagy of ovarian granulosa cells. MethodsReal-time polymerase chain reaction assay was used to analyze the expression levels of CTBP1-AS in peripheral blood leukocytes of 40 PCOS patients and 40 non-PCOS women and the CTBP1-AS expression in ovarian granulosa cells and transfect ovarian granulosa cells with pcDNA3.1-CTBP1-AS and si-CTBP1-AS, respectively. Consequently, the CCK-8 kit was used to analyze the effect of CTBP1-AS on the proliferation of ovarian granulosa cells. Moreover, Western blotting was used to detect the expression levels of autophagy-related proteins LC3II/I and P62. ResultThe CTBP1-AS expression in the peripheral blood of PCOS patients was higher compared with non-PCOS patients (P < 0.05). Furthermore, the CTBP1-AS expression of ovarian granulosa cells in PCOS patients was higher compared with non-PCOS patients (P < 0.05). Consequently, CTBP1-AS overexpression in ovarian granulosa cells promotes the proliferation of ovarian granulosa cells and autophagy levels (P < 0.05). The CTBP1-AS expression interference in ovarian granulosa cells can inhibit the proliferation of ovarian granulosa cells and autophagy levels (P < 0.05). ConclusionThe CTBP1-AS expression in peripheral blood and ovarian granulosa cells of PCOS patients significantly increased, and CTBP1-AS could promote the proliferation of ovarian granulosa cells and the level of autophagy.


2021 ◽  
Author(s):  
Tairen Chen ◽  
Mengjing Wu ◽  
Yuting Dong ◽  
Bin Kong ◽  
Yufang Cai ◽  
...  

Abstract Purpose: Whether FSH promotes follicle growth by inhibiting the Hippo signalling pathway.METHODS: Ovaries were cultured in vitro into a control group (no intervention), an FSH group (0.3 IU/mL FSH), and a VP group (10 µg/mL vetiporfin). HE staining and follicle counts were performed at each stage after 3 hours of in vitro culture. Immunohistochemistry was performed to study the expression levels of LATS2, YAP, PLATS2, and PYAP, and their expression levels in each group were also analysed by Western blot.The number of secondary follicles was significantly increased in the FSH group, the arrangement of granulosa cells was neater, the nuclear fixation was reduced, and the number of atretic follicles was decreased in the VP group. The number of secondary follicles was significantly increased, the number of atretic follicles was reduced, and granulosa cell nuclear consolidation was reduced in the VP+FSH group. Immunohistochemistry showed that LATS2 and YAP expression levels were significantly increased and PLATS2 and PYAP expression levels were relatively decreased in the FSH group, PYAP and PLATS2 expression levels were significantly increased and YAP expression was significantly decreased in the VP group, and YAP and LATS2 expression levels were significantly increased and PYAP and PLATS2 expression levels were significantly decreased in the VP+FSH group. By Western blot, LATS2 and YAP were elevated and PYAP and PLAT2 were decreased in the FSH group, LATS2 and YAP were decreased and PYAP and PLATS were significantly elevated in the VP group, and LATS2 and YAP were elevated and PYAP and PLATS2 were decreased in the VP+FSH group.CONCLUSION: FSH promotes follicle development by inhibiting the Hippo signalling pathway.


2008 ◽  
Vol 28 (12) ◽  
pp. 4080-4092 ◽  
Author(s):  
Ayumu Nakashima ◽  
Takeshi Kawamoto ◽  
Kiyomasa K. Honda ◽  
Taichi Ueshima ◽  
Mitsuhide Noshiro ◽  
...  

ABSTRACT DEC1 suppresses CLOCK/BMAL1-enhanced promoter activity, but its role in the circadian system of mammals remains unclear. Here we examined the effect of Dec1 overexpression or deficiency on circadian gene expression triggered with 50% serum. Overexpression of Dec1 delayed the phase of clock genes such as Dec1, Dec2, Per1, and Dbp that contain E boxes in their regulatory regions, whereas it had little effect on the circadian phase of Per2 and Cry1 carrying CACGTT E′ boxes. In contrast, Dec1 deficiency advanced the phase of the E-box-containing clock genes but not that of the E′-box-containing clock genes. Accordingly, DEC1 showed strong binding and transrepression on the E box, but not on the E′ box, in chromatin immunoprecipitation, electrophoretic mobility shift, and luciferase reporter assays. Dec1 −/− mice showed behavioral rhythms with slightly but significantly longer circadian periods under conditions of constant darkness and faster reentrainment to a 6-h phase-advanced shift of a light-dark cycle. Knockdown of Dec2 with small interfering RNA advanced the phase of Dec1 and Dbp expression, and double knockdown of Dec1 and Dec2 had much stronger effects on the expression of the E-box-containing clock genes. These findings suggest that DEC1, along with DEC2, plays a role in the finer regulation and robustness of the molecular clock.


Development ◽  
1997 ◽  
Vol 124 (17) ◽  
pp. 3263-3272 ◽  
Author(s):  
T. Roztocil ◽  
L. Matter-Sadzinski ◽  
C. Alliod ◽  
M. Ballivet ◽  
J.M. Matter

Genes encoding transcription factors of the helix-loop-helix family are essential for the development of the nervous system in Drosophila and vertebrates. Screens of an embryonic chick neural cDNA library have yielded NeuroM, a novel neural-specific helix-loop-helix transcription factor related to the Drosophila proneural gene atonal. The NeuroM protein most closely resembles the vertebrate NeuroD and Nex1/MATH2 factors, and is capable of transactivating an E-box promoter in vivo. In situ hybridization studies have been conducted, in conjunction with pulse-labeling of S-phase nuclei, to compare NeuroM to NeuroD expression in the developing nervous system. In spinal cord and optic tectum, NeuroM expression precedes that of NeuroD. It is transient and restricted to cells lining the ventricular zone that have ceased proliferating but have not yet begun to migrate into the outer layers. In retina, NeuroM is also transiently expressed in cells as they withdraw from the mitotic cycle, but persists in horizontal and bipolar neurons until full differentiation, assuming an expression pattern exactly complementary to NeuroD. In the peripheral nervous system, NeuroM expression closely follows cell proliferation, suggesting that it intervenes at a similar developmental juncture in all parts of the nervous system. We propose that availability of the NeuroM helix-loop-helix factor defines a new stage in neurogenesis, at the transition between undifferentiated, premigratory and differentiating, migratory neural precursors.


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