ABSTRACT
The follicular ovarian reserve, constituted by primordial follicles (PMFs), is established early in life, then keeps declining regularly along reproductive life. The maintenance of a normal ...female reproductive function implies the presence of a vast amount of dormant PMFs. This process involves a continuous repression of PMF activation into early growing follicle through the balance between factors activating the initiation of follicular growth, mainly actors of the PI3K signaling pathway, and inhibiting factors such as anti‐Müllerian hormone (AMH). Any disruption of this balance may induce follicle depletion and subsequent infertility. It has been recently proposed that cyclophosphamide (Cy), an alkylating agent commonly used for treating breast cancer, triggers PMF activation, further leading to premature ovarian insufficiency. Preventing chemotherapy‐induced ovarian dysfunction might represent an interesting option for preserving optimal chances of natural or medically assisted conceptions after healing. The aim of the present study was to evaluate, in a model of Cy‐treated pubertal mice, whether AMH administration might restrain PMF depletion. The counting of the total PMF number within mouse ovaries showed that recombinant AMH prevented Cy‐induced PMF loss. Western blot analysis revealed activation of PI3K signaling pathway after Cy administration. After AMH injection, FOXO3A phosphorylation, a main actor of PMF activation, was significantly decreased. Taken together, these results support a protective role of AMH against Cy‐induced follicular loss. We also provide evidence for a possible role of autophagy in the preservation of follicular pool reserve. Therefore, concomitant recombinant AMH administration during chemotherapy might offer a new option for preserving young patients' fertility.—Sonigo, C., Beau, I., Grynberg, M., Binart, N. AMH prevents primordial ovarian follicle loss and fertility alteration in cyclophosphamide‐treated mice. FASEB J. 33, 1278–1287 (2019). www.fasebj.org
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Cancer treatment, such as chemotherapy, induces early ovarian follicular depletion and subsequent infertility. In order to protect gametes from the gonadotoxic effects of chemotherapy, several ...fertility preservation techniques-such as oocyte or embryo cryopreservation with or without ovarian stimulation, or cryopreservation of the ovarian cortex-should be considered. However, these methods may be difficult to perform, and the future use of cryopreserved germ cells remains uncertain. Therefore, improving the methods currently available and developing new strategies to preserve fertility represent major challenges in the area of oncofertility. Animal and ovarian culture models have been used to decipher the effects of different cytotoxic agents on ovarian function and several theories regarding chemotherapy gonadotoxicity have been raised. For example, cytotoxic agents might (i) have a direct detrimental effect on the DNA of primordial follicles constituting the ovarian reserve and induce apoptosis; (ii) induce a massive growth of dormant follicles, which are then destroyed; or (ii) induce vascular ovarian damage. Thanks to improvements in the understanding of the mechanisms involved, a large number of studies have been carried out to develop molecules limiting the negative impact of chemotherapy on the ovaries.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Purpose
Our aim was to elucidate the mechanisms involved in follicle activation of the ovarian reserve after human ovarian tissue transplantation, with specific focus on the role of the effectors of ...the PI3K (mTOR and FOXO1) and Hippo (YAP) signaling pathways and whether they are somehow altered.
Methods
Frozen-thawed ovarian tissue was collected from six women (age 25–35 years) undergoing surgery for non-ovarian pathologies and divided into 4 fragments in each case: one for non-grafted controls and three for grafting to immunodeficient mice for 3, 7 and 21 days. The tissue was processed for hematoxylin and eosin staining, immunohistochemistry and immunofluorescence at different timepoints before and after grafting. Activation of the PI3K and Hippo signaling pathways was investigated by analysis of mTOR phosphorylation, FOXO1 cytoplasmic localization and YAP nuclear localization.
Results
No change in mTOR levels was observed in primordial follicles post-transplantation, but a significant upturn was recorded in growing follicles compared with primordial follicles, irrespective of grafting time. A higher percentage of primordial follicles was also found with FOXO1 in the cytoplasm after 3 days of transplantation than in non-grafted controls. Finally, a greater proportion of primordial follicles was detected with YAP in the nucleus at all timepoints after grafting.
Conclusions
This study supports the hypothesis that follicle activation may occur as an early event after transplantation, with follicle growth and death both contributing to the burnout phenomenon. This is the first time that the effectors of the PI3K and Hippo pathways have been investigated in grafted human ovarian tissue and their role in burnout documented.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
This paper analyzes the influence of the microwave pulse repetition frequency on the thermal burnout effect of a PIN diode limiting-amplifying system. Based on the study of the single-shot microwave ...pulse thermal burnout effect and by introducing a new assumption that the heat dissipation of the electric field energy and the nonequilibrium carrier energy during the microwave pulse intervals can be neglected, the theoretical thermal burnout model in our previous study is extended to be suitable for repetitive microwave pulses. The theoretical relationship among the pulse number, the pulse repetition frequency, the pulse width and the thermal burnout power threshold is obtained by theoretical derivation. Because the assumptions are introduced, the theoretical relationship requires that both the whole length of a repetitive microwave pulse and the pulse width in a cycle of a repetitive microwave pulse should be between 10 ns and 10 μs. The results obtained by the theoretical relationship are in good agreement with the simulation results obtained by our self-designed device-circuit joint simulator, which verifies the correctness of the theoretical analyses, modeling and derivation. By fitting at least two sets of simulation or experimental data, the theoretical relationship can be used to predict the thermal burnout power thresholds of PIN diode limiting-amplifying systems under microwave pulse injections with different pulse parameters. It can greatly reduce the simulation or experimental costs and could be helpful for the design of a radio frequency receiver.
•The influence of microwave pulse repetition frequency on the thermal burnout effect is analyzed.•The theoretical relationship of microwave pulse parameters is extended suitable for repetitive microwave pulses.•The theoretical results obtained in this paper can greatly reduce the simulation or experimental costs.•The theoretical results obtained in this paper could be helpful for the design of a radio frequency receiver.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The influence of microwave pulse power on the burnout effect of the AlGaN/GaN high electron mobility transistor (HEMT) in a low noise amplifier (LNA) is studied. The LNA constructed by an AlGaN/GaN ...HEMT is modeled by using our independent-developed device-circuit joint simulator. The correctness of our simulator is verified by comparing the simulated DC characteristics of the studied HEMT by using our simulator and two kinds of commercial software. The simulated gains obtained by using our simulator and the commercial software ADS are in agreement with the measured results. The results show that the relationship between the injected power and the actual absorbed power satisfies a linear relationship, and the burnout time decreases with the increase of the injected power.
Increasing the gas temperature at the inlet to the high pressure turbine of gas turbine engines is known as a proven method to increase the efficiency of these engines. However, this will expose the ...blades’ surface to very high heat load and thermal damages. In the case of the un-shrouded turbine blades, the blade tip will be exposed to a significant thermal load due to the developed leakage flows in the tip gap, this leads to in-service burnout which degrades the blade tip and shortens its operational life. This paper studies the in-service burnout effect of the transonic tip flows over a cavity tip which is a configuration commonly used to reduce the tip leakage flows. This investigation is carried out experimentally within a transonic wind tunnel and computationally using steady and unsteady Reynolds Averaged Navier Stokes approaches. Various flow measurements are established and different flow behaviour including separation bubbles, shockwave development and distinct flow interactions are captured and discussed. It is found that when the tip is exposed to the in-service burnout, leakage flow behaves in a significantly different way. In addition, the effective tip gap becomes much larger and allows higher leakage mass flow rate in comparison to the sharp-edge tip (i.e. a tip at the beginning of its operational life). The tip leakage losses are found much higher for the round-edge cavity tip (i.e. a tip exposed to burn-out effect). Experimental and computational flow visualisations, surface pressure measurements and discharge coefficient variation are given and analysed for several pressure ratios across the tip gap.
In this paper, the influence of microwave pulse width on the thermal burnout effect of a low noise amplifier (LNA) constructed by a GaAs pseudomorphic high electron mobility transistor (PHEMT) is ...theoretically analyzed and further verified with simulation and experimental results. By analyzing the electrical procedure and the thermal procedure, a theoretical model of the thermal burnout effect of the studied LNA is established according to the properties of microwave pulses and the structure of the LNA and GaAs PHEMT. Based on the theoretical model, the analytical relationship between the microwave pulse width and the thermal burnout power threshold is further obtained. According to the limitations caused by the approximations in the process of modeling, the available microwave pulse width range for the proposed analytical relationship is more than a nanosecond level and less than a microsecond level. The coefficients of the proposed analytical relationship can be determined by fitting at least two sets of simulation or experimental results, which can greatly reduce the simulation or experimental costs. Finally, the analytical relationship is verified by simulation and experimental results. The results show that the proposed analytical relationship is suitable to estimate the thermal burnout power threshold for a given microwave pulse width within the limit of microwave pulse width range.
•The mechanism of the microwave pulse thermal burnout effect on an LNA constructed by a GaAs PHEMT is analyzed.•The analytical relationship between the microwave pulse width and the thermal burnout power threshold is obtained.•The available pulse width range is determined according to the limitations caused by the approximations.•Using the analytical relationship can save great simulation or experimental costs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
This paper analyzes the influence of the microwave pulse width on the thermal burnout effect of a PIN diode limiting-amplifying system. Based on theoretical analyses and simulation, the relationship ...of the burnout effect on a PIN diode limiter and a PIN diode limiting-amplifying system is obtained first. By adopting an absorption efficiency factor, the theoretical model of the relationship between the microwave pulse width and the burnout power threshold for the PIN diode limiting-amplifying system is obtained. The proposed theoretical formulas can be determined by using at least two sets of simulation or measurement results to fit the constant coefficients, which can greatly reduce the simulation or experimental costs. The results obtained by the theoretical formulas are in good agreement with the numerical simulation results obtained by our self-designed device–circuit joint simulator, which verifies the correction of the theoretical analyses and modeling. The available microwave pulse width range for the proposed theoretical formulas is from 10ns to 10μs. In consideration of the potential threat of microwave pulses, the system-level study results obtained in this paper will be helpful for the design of the radio frequency receivers.
•The relationship of the burnout effect on a PIN diode limiter and a PIN diode limiting-amplifying system is obtained.•An absorption efficiency factor is adopted to establish the theoretical model.•The relationship between the microwave pulse width and the burnout power threshold is obtained.•The system-level study results obtained in this paper will be helpful for the design of the radio frequency receivers.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
PurposeThe purpose of this study was to examine the antecedents and consequences of burnout among the Ethiopian Civil Service University and Kotebe Metropolitan University instructors in ...Ethiopia.Design/methodology/approachThe study employed purely quantitative research and then used a cross-sectional survey design. Therefore, questionnaires adopted from the Maslach Burnout Inventory were collected from 158 university instructors.FindingsThe antecedents of burnout were a job, organizational and individual characteristics, whereas the consequences of burnout were job satisfaction, affective commitment and turnover intention. Work experience, educational status, job characteristics, organizational support and reward and recognition were reported as primary sources of burnout among instructors. Therefore, all the identified antecedents were correlated with burnout. Besides, turnover intention and affective commitment were the major consequences of burnout. Burnout partially mediated the relationship between the antecedents and consequences. Therefore, the antecedents directly impact burnout, but they also indirectly affect the consequences through burnout.Research limitations/implicationsThis study has a narrow geographical scope and is limited to a cross-sectional design. Therefore, a longitudinal study representing a large number of universities using mixed research is required to generalize about instructors' burnout in Ethiopia.Practical implicationsThis study helps to familiarize scholars, universities and researchers with instructors' burnout in Ethiopia. More specifically, the results of this study help the Ethiopian Civil Service University and Kotebe Metropolitan University to recognize the antecedents and consequences of burnout among their instructors and help them take corrective measures to address the problems of their employees as well as to improve efficiency and quality of education to the community through eliminating the antecedents.Originality/valueThis study gives a better understanding of burnout and becomes good literature on the magnitude and relationship of the antecedents and consequences of burnout among university instructors in Ethiopia. Thus, it provides a conceptual basement for research on university instructors' burnout in Ethiopia.
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