scholarly journals The Impact of Chemotherapy on the Ovaries: Molecular Aspects and the Prevention of Ovarian Damage

2019 ◽  
Vol 20 (21) ◽  
pp. 5342 ◽  
Author(s):  
Charlotte Sonigo ◽  
Isabelle Beau ◽  
Nadine Binart ◽  
Michaël Grynberg

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.

2019 ◽  
Vol 13 ◽  
pp. 117955811985475 ◽  
Author(s):  
Charlotte Sonigo ◽  
Isabelle Beau ◽  
Nadine Binart ◽  
Michael Grynberg

Anti-Müllerian hormone (AMH) is a member of the transforming growth factor (TGF)-beta family and a key regulator of sexual differentiation and folliculogenesis. While the serum AMH level has been used in reproductive medicine as a biomarker of quantitative ovarian reserve for more than 20 years, new potential therapeutic applications of recombinant AMH are emerging, notably in the field of oncofertility. Indeed, it is well known that chemotherapy, used to treat cancer, induces ovarian follicular depletion and subsequent infertility. Animal models have been used widely to understand the effects of different cytotoxic agents on ovarian function, and several hypotheses regarding chemotherapy gonadotoxicity have been proposed, that is, it might have a direct detrimental effect on the primordial follicles constituting the ovarian reserve and/or on the pool of growing follicles secreting AMH. Recently, a new mechanism of chemotherapy-induced follicular depletion, called the “burn-out effect,” has been proposed. According to this theory, chemotherapeutic agents may lead to a massive growth of dormant follicles which are then destroyed. As AMH is one of the factors regulating the recruitment of primordial follicles from the ovarian reserve, recombinant AMH administration concomitant with chemotherapy might limit follicular depletion, therefore representing a promising option for preserving fertility in women suffering from cancer. This review reports on the potential usefulness of AMH measurement as well as AMH’s role as a therapeutic agent in the field of female fertility preservation.


2011 ◽  
Vol 23 (1) ◽  
pp. 1 ◽  
Author(s):  
J. J. Ireland ◽  
G. W. Smith ◽  
D. Scheetz ◽  
F. Jimenez-Krassel ◽  
J. K. Folger ◽  
...  

The mechanism whereby the inherently high variation in ovary size and the total number of high-quality oocytes in ovaries (ovarian reserve) impact on ovarian function and fertility, diagnostics to measure the size of the ovarian reserve and the factors that cause variation in the ovarian reserve are unknown. Our results show that cattle can be phenotyped reliably based on the number of antral follicles growing during follicular waves (antral follicle count, AFC). Young adult cattle with a consistently low v. a high AFC have smaller gonads, a markedly diminished ovarian reserve and many other phenotypic characteristics usually associated with ovarian aging and infertility. A powerful new approach based on a single measurement of serum concentration of anti-Müllerian hormone (AMH) is described to test the longstanding hypothesis that the size of the ovarian reserve is positively associated with fertility. Also, new evidence shows that maternal environment has a critical role in regulation of the high variation in the ovarian reserve and perhaps fertility in offspring. These results support the conclusion that the inherently high variation in the ovarian reserve, potentially caused by alterations in the maternal environment, has a negative impact on ovarian function that may result in suboptimal fertility in young adult cattle, and a single AMH measurement can be used reliably in future studies to determine if fertility is suboptimal in young adult cattle with low circulating AMH concentrations and a correspondingly diminished ovarian reserve.


2019 ◽  
Vol 20 (2) ◽  
pp. 148-153
Author(s):  
David Ledingham ◽  
Michael Plant ◽  
Fayez Mustafa ◽  
Bhimanagouda Patil

Cytotoxic agents such as cyclophosphamide are infrequently used in neurological practice. When they are, it is commonly in critically ill patients or in those with refractory inflammatory disorders. Cyclophosphamide in particular has a well-recognised negative impact on both female and male long-term fertility. This article summarises the data with regards the impact of cytotoxics on long-term fertility and describes the current options to preserve fertility in these patients. We hope this will provide neurologists with a useful aid for counselling patients for whom they are considering these treatments.


2018 ◽  
Vol 14 (4) ◽  
pp. 467-470
Author(s):  
Norrabiátul Adawiyah Aziz ◽  
Fathimah Mohamad ◽  
Teh Lay Kek ◽  
Nuraliza Abdul Satar

Ovarian aging has been associated with increased oxidative stress leading to loss of ovarian function and infertility. Tocotrienol, a potent antioxidant, has been proven to exert beneficial effects in the female reproductive system. Serum metabolites were analyzed to examine the biochemical changes and to identify biomarkers related to reproductive aging that could lead to poor embryo quality and development. Female Mus musculus mice were divided into four groups. Six-month-old mice were given tocopherol-stripped corn oil as a vehicle control while other groups were supplemented orally with tocotrienol-rich fraction (TRF) at doses of 90, 120, and 150 mg/kg bodyweight for two months, respectively. After two months, mice from all groups were super ovulated, and euthanized. Embryos were collected at the 2-cell stage and cultured to monitor their development while serum was used for metabolomic analysis. The percentage of normal embryos and development of embryos to blastocyst stage were significantly higher in groups supplemented with TRF. A total of 71 metabolites that are related to reproductive aging were identified in all groups and significant changes were detected in metabolic pathways that include fatty acids, amino acids metabolism and steroid hormone biosynthesis. These changes suggest that aging has a negative impact on cellular energy storage, energy metabolism and oxidative stress that subsequently affect female fertility. Supplementation with TRF prevented the impact of age related metabolic changes on the embryo. Thus, it appears that TRF exerts a protective mechanism towards female reproductive aging.


Reproduction ◽  
2008 ◽  
Vol 136 (6) ◽  
pp. 691-701 ◽  
Author(s):  
Marvin L Meistrich ◽  
Gunapala Shetty

Methods to restore fertility of men and women sterilized by medical treatments and environmental toxicant exposures are under investigation. Rendering spermatogenesis and ovarian follicular development kinetically quiescent by suppression of gonadotropins has been proposed to protect them from damage by cytotoxic therapy. Although the method fails to protect the fertility of male mice and monkeys, gonadotropin and testosterone suppression in rats before or after cytotoxic therapy do enhance the recovery of spermatogenesis. However, the mechanism involves not the induction of quiescence but rather the reversal, by suppression of testosterone, of a block in differentiation of surviving spermatogonia caused by damage to the somatic environment. In men, only one of eight clinical trials was successful in protecting or restoring spermatogenesis after cytotoxic therapy. In women, protection of primordial follicles in several species from damage by cytotoxic agents using GnRH analogs has been claimed; however, only two studies in mice appear convincing. The protection cannot involve the induction of quiescence in the already dormant primordial follicle but may involve direct effects of GnRH analogs or indirect effects of gonadotropin suppression on the whole ovary. Although numerous studies in female patients undergoing chemotherapy indicate that GnRH analogs might be protective of ovarian function, none of the studies showing protection were prospective randomized clinical trials and thus they are inconclusive. Considering interspecies differences and similarities in the gonadal sensitivity to cytotoxic agents and hormones, mechanistic studies are needed to identify the specific beneficial effects of hormonal suppression in select animal models that may be applicable to humans.


2020 ◽  
Vol 103 (6) ◽  
pp. 1209-1216
Author(s):  
Selva L Luna ◽  
Donald I Brown ◽  
Steven G Kohama ◽  
Henryk F Urbanski

Abstract Dehydroepiandrosterone (DHEA) hormonal supplementation can improve oocyte quality in women with diminished ovarian function. However, it is unclear whether DHEA supplementation can also enhance ovarian function during the perimenopause (i.e., when the number of follicles in the ovary has undergone a marked reduction). To address this question, we examined the impact of 2.5-months of daily 5-mg oral DHEA supplementation on the number of ovarian follicles and the concentration of anti-Müllerian hormone (AMH) in perimenopausal rhesus macaques. Like women, these long-lived nonhuman primates have ~ 28-day menstrual cycles and eventually undergo menopause. They also show similar age-related neuroendocrine changes, including a marked decrease in circulating concentrations of DHEA and DHEA sulfate (DHEAS). Our experimental design involved the following three groups of animals (N = 6 per group): Young adult (mean age = 11.6 years), Old control (mean age = 23.1 years), and Old DHEA-treated (mean age = 23.5 years). Histological examination of the ovaries revealed a significant age-related decrease in the mean number of primordial follicles despite DHEA supplementation. Moreover, AMH concentrations within the ovaries and circulation, assessed by Western analysis and ELISA, respectively, showed significant age-related decreases that were not attenuated by DHEA supplementation. Taken together, these results fail to show a clear effect of short-term physiological DHEA supplementation on the perimenopausal ovary. However, they do not exclude the possibility that alternative DHEA supplementation paradigms (e.g., involving an earlier start date, longer duration and using pharmacological doses) may extend reproductive potential during aging.


2015 ◽  
Vol 26 (3-4) ◽  
pp. 116-123
Author(s):  
A. P. Korzh ◽  
T. V. Zahovalko

Recently, the number of published works devoted to the processes of synanthropization of fauna, is growing like an avalanche, which indicates the extreme urgency of this theme. In our view, the process of forming devices to coexist with human and the results of his life reflects the general tandency of the modern nature evolution. Urbanization is characteristic for such a specific group of animals like amphibians, the evidence of which are numerous literature data. Many researchers use this group to assess the bioindicative quality of the environment. For this aim a variety of indicators are used: from the cellular level of life of organization up to the species composition of the group in different territories. At the same time, the interpretation of the results is not always comparable for different areas and often have significantly different interpretations by experts. Urban environment, primarily due to the contamination is extremely aggressive to amphibians. As a consequence, the urban populations of amphibians may be a change in the demographic structure, affecting the reproductive ability of the population, the disappearance of the most sensitive species or individuals, resizing animals, the appearance of abnormalities in the development, etc. At the same time play an important amphibians in the ecosystems of cities, and some species in these conditions even feel relatively comfortable. Therefore, it is interesting to understand the mechanisms of self-sustaining populations of amphibians in urban environments. To assess the impact of natural and anthropogenic factors on the development of amphibian populations were used cognitive modeling using the program Vensim PLE. Cognitive map of the model for urban and suburban habitat conditions were the same. The differences concerned the strength of connections between individual factors (migration, fertility, pollution) and their orientation. In general, factors like pollution, parasites, predators had negative impact on the population, reducing its number. The birth rate, food and migration contributed to raising number of individuals. Some of the factors affected on the strength to of each other as well: the majority of the factors affected the structure of the population, had an influence on the fertility. Thanks to it the model reflects the additive effect of complex of factors on the subsequent status of the population. Proposed and analyzed four scenarios differing strength and duration of exposure. In the first scenario, a one-time contamination occurs and not subsequently repeated. The second and third scenario assumes half board contamination, 1 year (2 scenario) and two years (scenario 3). In the fourth scenario, the pollution affected the population of amphibians constantly. In accordance with the results of simulation, much weaker than the natural populations respond to pollution - have them as an intensive population growth and its disappearance at constant pollution is slow. Changes to other parameters of the model showed that this pollution is the decisive factor -only the constant action leads to a lethal outcome for the populations. All other components of the model have a corrective effect on the population dynamics, without changing its underlying trand. In urban areas due to the heavy impact of pollution maintaining the population is only possible thanks to the migration process – the constant replenishment of diminishing micropopulations of natural reserves. This confirms the assumption that the form of existence metapopulations lake frog in the city. In order to maintain the number of amphibians in urban areas at a high level it is necessary to maintain existing migration routes and the creation of new ones. Insular nature of the placement of suitable habitats in urban areas causes the metapopulation structure of the types of urbanists. Therefore, the process of urbanization is much easier for those species whicht are capable of migration in conditions of city. In the initial stages of settling the city micropopulationis formed by selective mortality of the most susceptible individuals to adverse effects. In future, maintaining the categories of individuals is provided mainly due to migration processes metapopulisation form of the species of existence is supported). It should be noted that the changes in the previous levels are always saved in future. In the case of reorganizations of individuals we of morphology can assume the existence of extremely adverse environmental conditions that threaten the extinction of the micropopulations. 


2020 ◽  
Vol 8 (3) ◽  
pp. 3-17
Author(s):  
Elena Blagoeva

The impact of the last global economic crisis (2008) on the European economy put a strain on higher education (HE), yet it also pushed the sector towards intensive reforms and improvements. This paper focuses on the “Strategy for the Development of Higher Education in the Republic of Bulgaria 2014-2020”. With a case study methodology, we explore the strategic endeavours of the Bulgarian government to comply with the European directions and to secure sustainable growth for the HE sector. Our research question is ‘How capable is the Bulgarian HE Strategy to overcome the economic and systemic restraints of Bulgarian higher education?’. Because the development of strategies for HE within the EU is highly contextual, a single qualitative case study was chosen as the research approach. HE institutions are not ivory towers, but subjects to a variety of external and internal forces. Within the EU, this is obviated by the fact that Universities obtain their funds from institutions such as governments, students and their families, donors, as well as EU-level programmes. Therefore, to explore how these pressures interact to affect strategic action on national level, the case method is well suited as it enabled us to study the phenomena thoroughly and deeply. The paper suggests the actions proposed within the Strategy have the potential to overcome the delay, the regional isolation and the negative impact of the economic crisis on the country. Nevertheless, the key elements on which the success or failure of this Strategy hinges are the control mechanisms and the approach to implementation. Shortcomings in these two aspects of strategic actions in HE seem to mark the difference between gaining long-term benefits and merely saving face in front of international institutions.


1997 ◽  
Vol 36 (4II) ◽  
pp. 947-957 ◽  
Author(s):  
Shahrukh Rafi Khan

This paper has a two-fold objective: first, to examine the terms on which Pakistan receives aid and whether its debt situation is sustainable, and second, to examine the impact of aid and debt on economic growth. It is found that there is little encouraging that can be said about how the terms on which Pakistan has received aid over time have changed, and its current debt situation is not sustainable. Also reported is the analysis done elsewhere which shows that aid has a negative (Granger) causal impact on GDP, and aid has a robust negative impact on economic growth after controlling for supplyside shocks. We provide various reasons for this negative association.


Author(s):  
Ajeng Embri Legawati ◽  
Nur Azizah ◽  
Achmad Ramadhan

Green beans cultivation technology using mice pets control has been implemented in the Gluranploso village, Benjeng Gresik. The implementation of the technology performed for 2.5 months from August to October 2017. The purpose of the implementation is aimed to reduce the dependence of farmers on the use of chemical pesticides so that the farmers are aware of the negative impact of chemical pesticides. Assessing the impact of the utilization of Bintaro fruit and fruit extracts to explore ways of making Bintaro as a natural biopesticide to overcome rat attack on green bean plants in the Gluranploso village. Pest control mice can reduce the rate of loss of the crops more effectively and efficiently. Finally, with the use of those natural resources as a biopesticide material can also maintain the environmental balance


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