scholarly journals Role of angiotensin in ovarian follicular development and ovulation in mammals: a review of recent advances

Reproduction ◽  
2012 ◽  
Vol 143 (1) ◽  
pp. 11-20 ◽  
Author(s):  
Paulo Bayard Gonçalves ◽  
Rogério Ferreira ◽  
Bernardo Gasperin ◽  
João Francisco Oliveira
Keyword(s):  
Vascular Function ◽  
Ovarian Function ◽  
Ovarian Tissue ◽  
Follicle Development ◽  
Ang Ii ◽  
Paracrine Factor ◽  
Vascular Control

Angiotensin (Ang) II is widely known for its role in the control of systemic blood vessels. Moreover, Ang II acts on the vascular control of ovarian function, corpus luteum formation, and luteolysis. Over the past 10 years, our research group has been studying the new concept of the renin–angiotensin system (RAS) as an autocrine/paracrine factor regulating steroidogenesis and promoting different cellular responses in the ovary, beyond vascular function. We have developed and used differentin vivoandin vitroexperimental models to study the role of RAS in the ovary and a brief overview of our findings is presented here. It is widely accepted that there are marked species differences in RAS function in follicle development. Examples of species-specific functions of the RAS in the ovary include the involvement of Ang II in the regulation of follicle atresia in rats vs the requirement of this peptide for the dominant follicle development and ovulation in rabbits and cattle. More recently, Ang-(1–7), its receptor, and enzymes for its synthesis (ACE2, NEP, and PEP) were identified in bovine follicles, implying that Ang-(1–7) has an ovarian function. Other novel RAS components (e.g. (pro)renin receptor and renin-binding protein) recently identified in the bovine ovary show that ovarian RAS is poorly understood and more complex than previously thought. In the present review, we have highlighted the progress toward understanding the paracrine and autocrine control of ovarian antral follicle development and ovulation by ovarian tissue RAS, focusing onin vivostudies using cattle as a model.

scholarly journals HIF-1α contributes to Ang II-induced inflammatory cytokine production in podocytes

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Hao Huang ◽  
Yanqin Fan ◽  
Zhao Gao ◽  
Wei Wang ◽  
Ning Shao ◽  
...  
Keyword(s):  
Hypoxia Inducible Factor ◽  
Renin Angiotensin System ◽  
Inflammatory Factors ◽  
Ang Ii ◽  
Angiotensin System ◽  
Inflammatory Injury ◽  
Tnf Α

Abstract Background Studies have indicated that changed expression of hypoxia-inducible factor-1α (HIF-1α) in epithelial cells from the kidney could affect the renal function in chronic kidney disease (CKD). As Angiotensin II (Ang II) is a critical active effector in the renin-angiotensin system (RAS) and was proved to be closely related to the inflammatory injury. Meanwhile, researchers found that Ang II could alter the expression of HIF-1α in the kidney. However, whether HIF-1α is involved in mediating Ang II-induced inflammatory injury in podocytes is not clear. Methods Ang II perfusion animal model were established to assess the potential role of HIF-1α in renal injury in vivo. Ang II stimulated podocytes to observe the corresponding between HIF-1α and inflammatory factors in vitro. Results The expression of inflammatory cytokines such as MCP-1 and TNF-α was increased in the glomeruli from rats treated with Ang II infusion compared with control rats. Increased HIF-1α expression in the glomeruli was also observed in Ang II-infused rats. In vitro, Ang II upregulated the expression of HIF-1α in podocytes. Furthermore, knockdown of HIF-1α by siRNA decreased the expression of MCP-1 and TNF-α. Moreover, HIF-1α siRNA significantly diminished the Ang II-induced overexpression of HIF-1α. Conclusion Collectively, our results suggest that HIF-1α participates in the inflammatory response process caused by Ang II and that downregulation of HIF-1α may be able to partially protect or reverse inflammatory injury in podocytes.

scholarly journals Salt-inducible Kinases Are Critical Determinants of Female Fertility

Endocrinology ◽  
2020 ◽  
Vol 161 (7) ◽  
Author(s):  
Marah Armouti ◽  
Nicola Winston ◽  
Osamu Hatano ◽  
Elie Hobeika ◽  
Jennifer Hirshfeld-Cytron ◽  
...  
Keyword(s):  
Ovarian Function ◽  
Follicle Stimulating Hormone ◽  
Female Fertility ◽  
Camp Signaling ◽  
Follicle Development ◽  
Pharmacological Modulation ◽  
Ovarian Granulosa Cells ◽  
Different Levels

Abstract Follicle development is the most crucial step toward female fertility and is controlled mainly by follicle-stimulating hormone (FSH). In ovarian granulosa cells (GCs), FSH activates protein kinase A by increasing 3′,5′-cyclic adenosine 5′-monophosphate (cAMP). Since cAMP signaling is impinged in part by salt-inducible kinases (SIKs), we examined the role of SIKs on the regulation of FSH actions. Here, we report that SIKs are essential for normal ovarian function and female fertility. All SIK isoforms are expressed in human and rodent GCs at different levels (SIK3>SIK2>SIK1). Pharmacological inhibition of SIK activity potentiated the stimulatory effect of FSH on markers of GC differentiation in mouse, rat, and human GCs and estradiol production in rat GCs. In humans, SIK inhibition strongly enhanced FSH actions in GCs of patients with normal or abnormal ovarian function. The knockdown of SIK2, but not SIK1 or SIK3, synergized with FSH on the induction of markers of GC differentiation. SIK inhibition boosted gonadotropin-induced GC differentiation in vivo, while the genomic knockout of SIK2 led to a significant increase in the number of ovulated oocytes. Conversely, SIK3 knockout females were infertile, FSH insensitive, and had abnormal folliculogenesis. These findings reveal novel roles for SIKs in the regulation of GC differentiation and female fertility, and contribute to our understanding of the mechanisms regulated by FSH. Furthermore, these data suggest that specific pharmacological modulation of SIK2 activity could be of benefit to treat ovulatory defects in humans and to increase the propagation of endangered species and farm mammals.

Influence of hormone environment and donor age on cryopreserved common wombat (Vombatus ursinus) ovarian tissue xenografted into nude mice

2004 ◽  
Vol 16 (7) ◽  
pp. 699 ◽  
Author(s):  
M. Cleary ◽  
J. M. Shaw ◽  
G. Jenkin ◽  
A. O. Trounson
Keyword(s):  
Nude Mice ◽  
Ovarian Tissue ◽  
Follicle Development ◽  
Kidney Capsule ◽  
Oocyte Collection ◽  
Common Wombat ◽  
Tissue Grafts ◽  
Gonadal Status

Developmentally competent oocytes can be collected from xenografted ovarian tissues; however, optimal xenograft conditions need to be established for this technique to be of use in assisted reproduction. In the present study, common wombat ovarian tissue was xenografted under the kidney capsule of nude mice to clarify the role of recipient gonadal status and donor tissue age on graft establishment, follicle development and oocyte recovery. Eighty-nine per cent of all grafts were recovered; of these, 78% contained growing follicles. In female graft recipients, follicle development to the antral stage occurred earlier in ovariectomised recipients compared with intact graft recipients. Similarly, follicle development occurred earlier in recipients of pouch young ovarian tissue grafts when compared with subadult xenografts. Follicle development proceeded to the antral stage in subadult grafts placed under the kidney capsule of male recipient mice, albeit at a slower rate than subadult grafts placed in female recipients. Oocytes were collected from grafts placed in female and male recipients, but no mature oocytes were observed at the time of collection, nor could these oocytes be matured in vitro. The present study demonstrated that common wombat pouch young tissue xenografted to female recipient mice, and subadult ovarian tissue xenografted to male recipient mice, can develop to the antral stage and can therefore facilitate oocyte collection. However, mature oocytes were not obtained using the current protocol.

scholarly journals COX-2 mediates angiotensin II-induced (pro)renin receptor expression in the rat renal medulla

2014 ◽  
Vol 307 (1) ◽  
pp. F25-F32 ◽  
Author(s):  
Fei Wang ◽  
Xiaohan Lu ◽  
Kexin Peng ◽  
Li Zhou ◽  
Chunling Li ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Protein Expression ◽  
Renal Medulla ◽  
Receptor Expression ◽  
Ang Ii ◽  
Cox 2 ◽  
Renin Content

(Pro)renin receptor (PRR) is predominantly expressed in the distal nephron where it is activated by angiotensin II (ANG II), resulting in increased renin activity in the renal medulla thereby amplifying the de novo generation and action of local ANG II. The goal of the present study was to test the role of cycloxygenase-2 (COX-2) in meditating ANG II-induced PRR expression in the renal medulla in vitro and in vivo. Exposure of primary rat inner medullary collecting duct cells to ANG II induced sequential increases in COX-2 and PRR protein expression. When the cells were pretreated with a COX-2 inhibitor NS-398, ANG II-induced upregulation of PRR protein expression was almost completely abolished, in parallel with the changes in medium active renin content. The inhibitory effect of NS-398 on the PRR expression was reversed by adding exogenous PGE2. A 14-day ANG II infusion elevated renal medullary PRR expression and active and total renin content in parallel with increased urinary renin, all of which were remarkably suppressed by the COX-2 inhibitor celecoxib. In contrast, plasma and renal cortical active and total renin content were suppressed by ANG II treatment, an effect that was unaffected by COX-2 inhibition. Systolic blood pressure was elevated with ANG II infusion, which was attenuated by the COX-2 inhibition. Overall, the results obtained from in vitro and in vivo studies established a crucial role of COX-2 in mediating upregulation of renal medullary PRR expression and renin content during ANG II hypertension.

Abstract 376: Downregulation of Endogenous Apelinergic Axis Mediates Endothelial and Organismal Senescence

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Rahul Rai ◽  
Asish K Ghosh ◽  
Layton H Smith ◽  
Douglas E Vaughan
Keyword(s):  
Endothelial Cells ◽  
Replicative Senescence ◽  
Cell Types ◽  
Ang Ii ◽  
Systematic Assessment ◽  
Multiple Cell ◽  
Deficient Mice

Background: Apelinergic signaling is a recently discovered GPCR mediated pathway. Endothelial cells are the main source of endogenous apelin (apln) while apelin receptor (aplnr) is present on multiple cell types. Since the role of endogenous apelinergic pathway within the context of senescence is largely unknown, we ask if levels of apln- aplnr vary with aging. We also investigate the effects of downregulated apln- aplnr on cellular and organismal aging. Approach and Results: To assess variations in endogenous apln- aplnr with aging, we compared their levels in 1 month (young) and 1 year old (old) WT mice. We noticed significant downregulation of apln- aplnr with chronological senescence in multiple tissues. Expression of apelin was also reduced with replicative senescence of endothelial cells. L-NAME administration, a model of stress induced senescence, also repressed aortic and cardiac apln. To address the mechanism involved in downregulation of apln- aplnr, we administered young wild type mice with Ang II. After a week of Ang II, there was significant downregulation of aortic apln and aplnr. Ang II and TGF-β also repressed apln and aplnr in vitro . Next we investigated the effects of downregulated apln on endothelial cells. In response to shRNA mediated apelin knockdown, cells exhibited slower proliferation and upregulated senescence associated markers. We observed similar results when endothelial aplnr was blocked with an antagonist, ML221. In addition, apln and aplnr deficient mice also exhibited features of cardiovascular aging, including ventricular hypertrophy and lower EF. Importantly, aplnr deficient mice at eight months of age were also hypertensive. Conclusion: We provide a systematic assessment of senescence associated variation in levels of apln- aplnr. We demonstrate the role of Ang II- TGF-β axis in downregulating apln- aplnr during chronological and stress induced senescence in vivo and in vitro . We propose a novel model of Ang II- TGF-β induced senescence. Where in, with aging Ang II and TGF-β repress endogenous apln- aplnr. Downregulation of endogenous apln- aplnr axis decreases beneficial “youthful” effects of apelin, resulting in endothelial dysfunction and accelerated organismal aging.

Abstract 348: Inhibition Of Phosphodiesterase 5 Attenuates Angiotensin II-dependent Hypertension And Renal Vascular Dysfunction In C57bl/6 Mice But Not In Enos-Ko Mice

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Manuel Thieme ◽  
Sema Sivritas ◽  
Sebastian A Potthoff ◽  
Evanthia Mergia ◽  
Lars C Rump ◽  
...  
Keyword(s):  
Vascular Function ◽  
Vascular Tone ◽  
Vascular Dysfunction ◽  
Pivotal Role ◽  
Ang Ii ◽  
Cgmp Signaling ◽  
Renal Vascular ◽  
The Impact

The kidney plays an outstanding role in the blood pressure (BP) regulation. The renal vasoconstrictor response to angiotensin (Ang) II is balanced by the NO/cGMP-signalling cascade. Ang II causes hypertension and vascular dysfunction by reducing cGMP sensitivity. Ang II is able to increase cGMP degradation by activating phosphodiesterase (PDE)1 and PDE5. The aim of the present study was to identify the predominant PDE subunit regulating renal blood flow (RBF) and vascular tone during hypertension. Therefore, we tested in vivo effects of acute PDE1 (vinpocetine) and PDE5 (sildenafil) inhibition at baseline and during acute Ang II infusion (200ng/kg/min). Furthermore, we examined the impact of PDE-inhibition on Ang II dependent hypertension (500ng/kg/min; 14 days) and on renal vascular function in the isolated perfused kidney. Acute vinpocetine administration (0.8-800μg/kg BW) showed almost no effect on systemic BP and RBF at baseline and during acute Ang II infusion. In contrast, sildenafil (0.8-800μg/kg BW) significantly decreased BP under baseline conditions. During acute Ang II infusion, BP reduction and RBF increase induced by sildenafil was even more pronounced suggesting a pivotal role of the PDE5 in the regulation of renal vascular tone. Based on these results, we tested whether inhibition of the PDE5 protects from hypertension and vascular dysfunction. Indeed, chronic sildenafil treatment significantly attenuated Ang II dependent hypertension in C57BL/6 (vehicle vs. sil: 156±4 vs. 139±7; p<0.05). Moreover, Sildenafil treatment significantly improved NO-dependent vasorelaxation in kidneys of Ang II- treated C57BL/6. To confirm that PDE5 is activated by an increased NO/cGMP signaling, we used eNOS-KO mice, a model known for decreased NO dependent cGMP generation. In eNOS-KO mice, sildenafil failed to reduce Ang II dependent hypertension (172,4 ± 4,3 mmHg vs. 166,1 ± 3,8 mmHg, p=0,2753) and did not improve vascular dysfunction in Ang II treated kidneys. In summary, the PDE5 is the predominant PDE regulating RBF. Inhibition of PDE5 by sildenafil ameliorates chronic Ang II dependent hypertension and improves vascular dysfunction. This study reveals new evidence for the pivotal role of PDE5 in the pathogenesis of AngII-induced hypertension.

Abstract 16434: IL-6 Signaling is Crucial for Cardiomyocyte Hypertrophy and Left Ventricular Dysfunction Induced by Pressure Overload

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Lin Zhao ◽  
Guangming Cheng ◽  
Yanjuan Yang ◽  
Anweshan Samanta ◽  
Rizwan R Afzal ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Cardiomyocyte Hypertrophy ◽  
Lv Function ◽  
Ang Ii ◽  
Adult Cardiomyocytes

Introduction: Interleukin-6 (IL-6), a proinflammatory cytokine, has been implicated in ischemic cardiac pathologies. Very little is currently known regarding the role of IL-6 signaling in pathological cardiomyocyte hypertrophy and LV dysfunction. Hypothesis: We hypothesized that IL-6 signaling plays a central role in cardiomyocyte hypertrophy and exerts a deleterious impact on LV remodeling induced by pressure overload. Methods: In vitro, adult cardiomyocytes from C57BL/6 (WT, control) and IL-6 knockout (KO) mice were stimulated by IL-6 and pro-hypertrophic agent angiotensin II (Ang II). The expression of hypertrophy markers and related signaling molecules were examined by real-time quantitative RT-PCR. In vivo, weight-matched male WT and IL-6 KO mice underwent transverse aortic constriction (TAC) or a sham procedure. Serial echocardiograms and a terminal hemodynamic study were performed. Results: After exposure to IL-6 and hypertrophic agonists, the expression of hypertrophy related genes, BNP, GATA-4, αSK actin, and β-MHC increased significantly in WT cardiomyocytes (Fig). These effects were significantly attenuated in IL-6 knockout cardiomyocytes (Fig), indicating an essential role of IL-6 in cardiomyocyte hypertrophy. In vivo, the worsening in LV contraction as well as relaxation after TAC was significantly attenuated in IL-6 KO mice, indicating superior preservation of LV function in the setting of pressure overload in the absence of IL-6 signaling. Conclusions: The protection against Ang II-induced hypertrophy observed in IL-6 KO adult cardiomyocytes in vitro, and in hearts of IL-6 KO mice after TAC in vivo illustrates a crucial role played by IL-6 in pathogenesis of pressure overload-induced LV hypertrophy. Modulation of IL-6 signaling may have preventive therapeutic potential for countless hypertensive patients at risk for LV hypertrophy and failure.

Angiotensin II binding sites in aortic endothelium of domestic fowl

1990 ◽  
Vol 258 (3) ◽  
pp. R777-R782 ◽  
Author(s):  
J. N. Stallone ◽  
H. Nishimura ◽  
A. Nasjletti
Keyword(s):  
Angiotensin Ii ◽  
Domestic Fowl ◽  
Angiotensin Receptors ◽  
Ang Ii ◽  
Aortic Endothelium ◽  
Specific Receptors ◽  
Layer Chromatography

In domestic fowl, angiotensin II (ANG II) produces a unique vasodepressor response in vivo and endothelium-dependent relaxation of aortic rings in vitro that appear to be a direct effect on vascular smooth muscle mediated through vascular angiotensin receptors. To explore the possible role of the endothelium in ANG II-induced vasodilation, ANG II binding to aortic membrane fractions and intact endothelium and prostaglandin (PG) production were examined in fowl aortas. 125I-[Ile5]ANG II binding by endothelium-intact aortic membrane fractions was consistently higher than binding by identically prepared endothelium-deleted membrane fractions at virtually all concentrations of ligand (10 pM-0.20 microM). Incubation of intact aortic rings with 125I-[Ile5]ANG II (0.50 nM) resulted in specific endothelial binding that increased linearly with time from 5.5 +/- 1.7 (SE) fmol/mg protein at 5 min to 13.7 +/- 1.8 at 30 min. Endothelial ANG II binding increased linearly with the dose of ligand, from 2.7 +/- 0.3 fmol/mg protein at 0.1 nM to 21.0 +/- 2.2 at 1.0 nM. Specific ANG II binding to aortic endothelium was competitively displaced 73 +/- 11% by unlabeled ANG II (0.1 microM) but not by bradykinin (0.1 microM). Incubation of intact aortic rings with [14C]arachidonic acid resulted in the formation of radioactive metabolites that comigrated in thin-layer chromatography with authentic PGE2 but not with 6-keto-PGF1 alpha. PGE2 production by aortic rings (44.4 +/- 4.5 ng.mg dry tissue-1.h-1) was not stimulated by addition of ANG II. These results suggest that specific receptors for ANG II exist in fowl aortic endothelium and that PGs are not involved in ANG II-induced vasodilation of the fowl aorta.

scholarly journals Curcumin in Combination with Aerobic Exercise Improves Follicular Dysfunction via Inhibition of the Hyperandrogen-Induced IRE1α/XBP1 Endoplasmic Reticulum Stress Pathway in PCOS-Like Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-22
Author(s):  
Yaling Zhang ◽  
Yajing Weng ◽  
Daojuan Wang ◽  
Rong Wang ◽  
Lihui Wang ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Aerobic Exercise ◽  
Ovarian Function ◽  
Polycystic Ovary ◽  
Ovarian Tissue ◽  
Oral Intake ◽  
Follicle Development ◽  
Sprague Dawley

Combining diet with exercise can improve health and performance. Exercise can reduce androgen excess and insulin resistance (IR) in polycystic ovary syndrome (PCOS) patients. Curcumin is also presumed to improve the follicle development disorder. Here, we investigated the effects of a combination therapy of oral intake of curcumin and exercise on hyperandrogen-induced endoplasmic reticulum (ER) stress and ovarian granulosa cell (GC) apoptosis in rats with PCOS. We generated a PCOS model via continuous dehydroepiandrosterone subcutaneous injection into the necks of Sprague Dawley rats for 35 days. PCOS-like rats then received curcumin treatment combined with aerobic (treadmill) exercise for 8 weeks. We found that compared to control rats, the ovarian tissue and ovarian GCs of hyperandrogen-induced PCOS rats showed increased levels of ER stress-related genes and proteins. Hyperandrogen-induced ovarian GC apoptosis, which was mediated by excessive ER stress and unfolded protein response (UPR) activation, could cause follicle development disorders. Both curcumin gavage and aerobic exercise improved ovarian function via inhibiting the hyperandrogen-activated ER stress IRE1α-XBP1 pathway. Dihydrotestosterone- (DHT-) induced ER stress was mitigated by curcumin/irisin or 4μ8C (an ER stress inhibitor) in primary GC culture. In this in vitro model, the strongly expressed follicular development-related genes Ar, Cyp11α1, and Cyp19α1 were also downregulated.

scholarly journals The Role of Anti-Müllerian Hormone (AMH) During Follicle Development in a Monovulatory Species (Sheep)

Endocrinology ◽  
2012 ◽  
Vol 153 (9) ◽  
pp. 4533-4543 ◽  
Author(s):  
Bruce K. Campbell ◽  
M. Clinton ◽  
R. Webb
Keyword(s):  
Functional Relationship ◽  
Primordial Follicle ◽  
Active Immunization ◽  
Follicle Development ◽  
Antral Follicles ◽  
Therapeutic Value ◽  
Clinical Interest

Knockout studies in mice have suggested that anti-Müllerian hormone (AMH) modulates primordial follicle recruitment and the response of growing follicles to FSH. Little is known of the physiology of AMH in monovular species, despite intense clinical interest in this factor. Using sheep as a model, we sought to investigate the functional role of AMH in modulating follicle development in monovular species. In contrast to the rodent, the results indicate that AMH does not affect the rate of primordial follicle recruitment but appears to regulate the rate at which follicles progress through the gonadotropin-responsive phase, during which it is maximally expressed. Thus, knockdown of AMH bioactivity by active immunization lead to a decline in the population of gonadotropin-responsive preantral and small antral follicles (P &lt; 0.01) and increases in both the number of gonadotropin-dependent antral follicles (P &lt; 0.01) and ovulation rate (P &lt; 0.05). These in vivo findings were consistent with the results of other studies examining the pattern of expression of AMH, which was negatively correlated with aromatase (P &lt; 0.001), and in vitro supplementation experiments, which supported an inhibitory role for AMH in modulating the response of both theca and granulosa cells to LH and FSH, respectively. The elucidation of a functional relationship between AMH and LH-stimulated thecal androgen production may be significant in terms of the etiology of common forms of anovulatory infertility in women. Furthermore, the observed increase in both the number of recruitable antral follicles and ovulatory quota in response to AMH knockdown may have therapeutic value in women who respond poorly to ovarian stimulation.

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