scholarly journals Exposure of Female Macaques to Western-Style Diet With or Without Chronic T In Vivo Alters Secondary Follicle Function During Encapsulated 3-Dimensional Culture

Endocrinology ◽  
2015 ◽  
Vol 156 (3) ◽  
pp. 1133-1142 ◽  
Author(s):  
Jing Xu ◽  
Whitney K. McGee ◽  
Cecily V. Bishop ◽  
Byung S. Park ◽  
Judy L. Cameron ◽  
...  

Abstract Increased adiposity and hyperandrogenemia alter reproductive parameters in both animal models and women, but their effects on preantral follicles in the ovary remain unknown. We recently reported that Western-style diet (WSD) consumption over 1 year, with or without chronic exposure to elevated circulating T, increased the body fat percentage, elicited insulin resistance, suppressed estradiol and progesterone production, as well as altered the numbers, size, and dynamics of antral follicles in the ovary during the menstrual cycle in female macaques. Therefore, experiments were designed to compare the WSD and WSD+T effects to age-matched controls on the survival, growth, and function of isolated secondary follicles during 5 weeks of encapsulated 3-dimensional culture. Follicle survival significantly declined in the WSD and WSD+T groups compared with the control (CTRL) group. Although media progesterone levels were comparable among groups, androstenedione and estradiol levels were markedly reduced in the WSD and WSD+T groups compared with the CTRL group at week 5. Anti-Müllerian hormone levels peaked at week 3 and were lower in the WSD+T group compared with the WSD or CTRL group. Vascular endothelial growth factor levels also decreased at week 5 in the WSD+T group compared with the WSD or CTRL group. After human chorionic gonadotropin exposure, only antral follicles developed from the CTRL group yielded metaphase II oocytes. Thus, WSD with or without T exposure affects the cohort of secondary follicles in vivo, suppressing their subsequent survival, production of steroid hormones and local factors, as well as oocyte maturation in vitro.

Author(s):  
Walter Bonani ◽  
Claudio Migliaresi ◽  
Wei Tan

Essential to growing or regenerating 3-dimensional tissues is the formation of functional microcirculation that provides nutrients, oxygen and signal molecules for tissue survival and function regeneration. In the past decade, molecule-based microvascular formation has been achieved in vitro and in vivo. However, direct delivery of angiogenic molecules often results in malformed hyperpermeable microvessels, microvessels with low density. This can be attributed to the lack of effective molecule mechanisms that regulate vascular formation. More recent studies utilize biodegradable materials to control the delivery of biomolecules for vascularization of engineered or ischemic tissues, and exciting results have shown the importance of molecule kinetics to the vascular formation. Molecule delivery mechanisms that mimic precisely-regulated spatiotemporal signaling events during natural vascularization may be a possible way to improve or optimize the process. Hence, this study is designed to develop a new release system capable of degrading in the body and releasing biomolecules in a spatiotemporally controlled manner.


Author(s):  
Silvia Martin-Almedina ◽  
Peter Mortimer ◽  
Pia Ostergaard

Primary lymphedema is a long-term (chronic) condition characterized by tissue lymph retention and swelling that can affect any part of the body, although it usually develops in the arms or legs. Due to the relevant contribution of the lymphatic system to human physiology, while this review mainly focusses on the clinical and physiological aspects related to the regulation of fluid homeostasis and edema, clinicians need to know that the impact of lymphatic dysfunction with a genetic origin can be wide ranging. Lymphatic gene dysfunction can affect immune function so leading to infection; it can influence cancer development and spread; and it can determine fat transport so impacting on nutrition and obesity. Genetic studies and the development of imaging techniques for the assessment of lymphatic function have enabled the recognition of primary lymphedema as a heterogenic condition in terms of genetic causes and disease mechanisms. In this review, the known biological function of several genes crucial to the development and function of the lymphatic system are used as a basis for understanding normal lymphatic biology. The disease conditions originating from mutations in these genes are discussed together with a detailed clinical description of the phenotype and the up-to-date knowledge in terms of disease mechanisms acquired from in vitro and in vivo research models.


2019 ◽  
Vol 56 (6) ◽  
pp. 753-759
Author(s):  
N. M. Savushkina ◽  
E. A. Galushko ◽  
N. V. Demidova ◽  
A. V. Gordeev

At present, the role of the renin-angiotensin system (RAS) in regulating the cardiovascular system and maintaining water and electrolyte homeostasis has been well studied. However, over the past decades, new components of the RAS have been identified, suggesting a wider range of its potential effects on the body. It is of fundamentally importance for rheumatologists to affect inflammation, including rheumatoid inflammation, through blockade of angiotensin (AT) II formation via the effects of AT 1–7 and angiotensin-converting enzyme inhibitors, as well as through suppression of angiogenesis, primarily by reducing the production of endothelial growth factor. The organ-protective and antiinflammatory potential of drugs that reduce the production of AT, which has been proven in in vitro and in vivo experiments, allows us to consider them as first-line angiotropic agents in patients with rheumatoid arthritis, especially in the presence of concomitant hypertension and/or nephropathy.


Leonardo ◽  
2015 ◽  
Vol 48 (3) ◽  
pp. 270-271
Author(s):  
Miranda D. Grounds

The contraction of specialized skeletal muscle cells results in classic movements of bones and other parts of the body that are vital for life. There is exquisite control over the movement of diverse types of muscles. This paper indicates the way in which skeletal muscles (myofibres) are formed; then factors that contribute to generating the movement are outlined: these include the nerve, sarcomeres, cytoskeleton, cell membrane and the extracellular matrix. The factors controlling the movement of mature myofibres in 3-dimensional tissues in vivo are vastly more complex than for tissue cultured immature muscle cells in an artificial in vitro environment.


2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Wenjuan Li ◽  
Ruxing Zhao ◽  
Jidong Liu ◽  
Meng Tian ◽  
Yiran Lu ◽  
...  

Pancreatic islet transplantation is a promising therapy to regain glycemic control in diabetic patients. The selection of ideal grafts is the basis to guarantee short-term effectivity and longevity of the transplanted islets. Contradictory to the traditional notion, recent findings implied the superiority of small islets for better transplantation outcomes rather than the large and intact ones. However, the mechanisms remain to be elucidated. Recent evidences emphasized the major impact of microcirculation on isletβ-cell mass and function. And potentials in islet graft revascularization are crucial for their survival and preserved function in the recipient. In this study, we verified the distinct histological phenotype and functionality of small islets versus large ones both in vitro and in vivo. With efforts to exploring the differences in microcirculation and revascularization of islet grafts, we further evaluated local expressions of angiotensin and vascular endothelial growth factor A (VEGF-A) at different levels. Our findings reveal that, apart from the higher density of insulin-producingβ-cells, small islets express less angiotensin and more angiotrophic VEGF-A. We therefore hypothesized a logical explanation of the small islet superiority for transplantation outcome from the aspects of facilitated microcirculation and revascularization intrinsically in small islets.


Author(s):  
Hazel Y. Stevens ◽  
Annie C. Bowles ◽  
Carolyn Yeago ◽  
Krishnendu Roy

Mesenchymal stromal cells (MSCs) have been widely investigated for regenerative medicine applications, from treating various inflammatory diseases as a cell therapy to generating engineered tissue constructs. Numerous studies have evaluated the potential effects of MSCs following therapeutic administration. By responding to their surrounding microenvironment, MSCs may mediate immunomodulatory effects through various mechanisms that directly (i.e., contact-dependent) or indirectly (i.e., paracrine activity) alter the physiology of endogenous cells in various disease pathologies. More specifically, a pivotal crosstalk between MSCs and tissue-resident macrophages and monocytes (TMφ) has been elucidated using in vitro and in vivo preclinical studies. An improved understanding of this crosstalk could help elucidate potential mechanisms of action (MOAs) of therapeutically administered MSCs. TMφ, by nature of their remarkable functional plasticity and prevalence within the body, are uniquely positioned as critical modulators of the immune system – not only in maintaining homeostasis but also during pathogenesis. This has prompted further exploration into the cellular and molecular alterations to TMφ mediated by MSCs. In vitro assays and in vivo preclinical trials have identified key interactions mediated by MSCs that polarize the responses of TMφ from a pro-inflammatory (i.e., classical activation) to a more anti-inflammatory/reparative (i.e., alternative activation) phenotype and function. In this review, we describe physiological and pathological TMφ functions in response to various stimuli and discuss the evidence that suggest specific mechanisms through which MSCs may modulate TMφ phenotypes and functions, including paracrine interactions (e.g., secretome and extracellular vesicles), nanotube-mediated intercellular exchange, bioenergetics, and engulfment by macrophages. Continued efforts to elucidate this pivotal crosstalk may offer an improved understanding of the immunomodulatory capacity of MSCs and inform the development and testing of potential MOAs to support the therapeutic use of MSCs and MSC-derived products in various diseases.


Endocrinology ◽  
2010 ◽  
Vol 151 (12) ◽  
pp. 5905-5915 ◽  
Author(s):  
Samantha A. Garside ◽  
Jack Henkin ◽  
Keith D. Morris ◽  
Suzanne M. Norvell ◽  
Fiona H. Thomas ◽  
...  

Using a novel in vitro angiogenesis assay, we previously showed that thrombospondin (TSP)-1 has antiangiogenic effects on rat follicles and induces apoptosis in granulosa cells in vitro. ABT-898 is an octapeptide mimetic of TSP-1 closely related to ABT-510. Here, we demonstrate the inhibitory effects of ABT-898 on follicular angiogenesis and its proapoptotic effect on granulosa cells. To investigate the potential of this peptide to inhibit follicular angiogenesis in vivo, marmoset monkeys were treated with 2.5 mg/kg ABT-898 twice daily throughout the follicular phase of the cycle. Although treatment did not block emergence of dominant follicles, angiogenesis was reduced in preantral and early-antral follicles. Furthermore, the incidence of atresia at these follicle stages was increased. To investigate whether treatment with ABT-898 would interfere with the timing or duration of the normal ovulatory rise in plasma progesterone, marmosets were treated with a depot formulation containing 25 mg ABT-898 at the start of the follicular phase, with a second injection after 2 wk. Despite active concentrations of peptide being maintained in the circulation, no apparent effects on the ovulatory cycle were observed. Taken together, these results indicate that ABT-898 is capable of having a dual effect by inhibiting follicular angiogenesis and promoting atresia of antral follicles in vivo but does not prevent ovulation or induce luteolysis, as has been observed with direct vascular endothelial growth factor inhibitors. These results suggest that ABT-898 could be a novel therapeutic to inhibit abnormal angiogenesis and induce atresia of accumulated follicles in polycystic ovary syndrome.


2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.


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