Synergistic effect of melatonin and ghrelin in preventing cisplatin-induced ovarian damage via regulation of FOXO3a phosphorylation and binding to thep27Kip1promoter in primordial follicles

2017 ◽  
Vol 63 (3) ◽  
pp. e12432 ◽  
Author(s):  
Hoon Jang ◽  
Younghwa Na ◽  
Kwonho Hong ◽  
Sangho Lee ◽  
Sohyeon Moon ◽  
...  
Keyword(s):  
Synergistic Effect ◽  
Primordial Follicles ◽  
Ovarian Damage

scholarly journals Ovarian Follicle Depletion Induced by Chemotherapy and the Investigational Stages of Potential Fertility-Protective Treatments—A Review

2019 ◽  
Vol 20 (19) ◽  
pp. 4720 ◽  
Author(s):  
Xia Hao ◽  
Amandine Anastácio ◽  
Kui Liu ◽  
Kenny A. Rodriguez-Wallberg
Keyword(s):  
Current Knowledge ◽  
Ovarian Follicle ◽  
Chemotherapeutic Agents ◽  
Premature Menopause ◽  
Primordial Follicles ◽  
Current Experimental Data ◽  
Vessel Network ◽  
Ovarian Damage ◽  
Experimental Stage

Ovarian follicle pool depletion, infertility, and premature menopause are all known sequelae of cancer treatment that negatively impact the quality of life of young cancer survivors. The mechanisms involved in this undesired iatrogenic ovarian damage have been intensively studied, but many of them remain unclear. Several chemotherapeutic drugs have been shown to induce direct and indirect DNA-damage and/or cellular stress, which are often followed by apoptosis and/or autophagy. Damage to the ovarian micro-vessel network induced by chemotherapeutic agents also seems to contribute to ovarian dysfunction. Another proposed mechanism behind ovarian follicle pool depletion is the overactivation of primordial follicles from the quiescent pool; however, current experimental data are inconsistent regarding these effects. There is great interest in characterizing the mechanisms involved in ovarian damage because this might lead to the identification of potentially protective substances as possible future therapeutics. Research in this field is still at an experimental stage, and further investigations are needed to develop effective and individualized treatments for clinical application. This review provides an overview of the current knowledge and the proposed hypothesis behind chemotherapy-induced ovarian damage, as well as current knowledge on possible co-treatments that might protect the ovary and the follicles from such damages.

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
Keyword(s):  
Ovarian Function ◽  
Negative Impact ◽  
Cytotoxic Agents ◽  
Embryo Cryopreservation ◽  
Primordial Follicles ◽  
Massive Growth ◽  
Culture Models ◽  
Ovarian Damage ◽  
Molecular Aspects ◽  
The Impact

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.

scholarly journals Differential sensitivity of inbred mouse strains to ovarian damage in response to low-dose total body irradiation†

2019 ◽  
Vol 102 (1) ◽  
pp. 133-144 ◽  
Author(s):  
Natalie Quan ◽  
Lacey R Harris ◽  
Ritika Halder ◽  
Camille V Trinidad ◽  
Brian W Johnson ◽  
...  
Keyword(s):  
Total Body Irradiation ◽  
Inbred Mouse ◽  
Differential Sensitivity ◽  
Mouse Strains ◽  
Inbred Mouse Strains ◽  
Primordial Follicles ◽  
Organ Systems ◽  
Ovarian Damage ◽  
Total Body ◽  
Strain Dependent

Abstract Radiation induces ovarian damage and accelerates reproductive aging. Inbred mouse strains exhibit differential sensitivity to lethality induced by total body irradiation (TBI), with the BALB/cAnNCrl (BALB/c) strain being more sensitive than the 129S2/SvPasCrl (129) strain. However, whether TBI-induced ovarian damage follows a similar pattern of strain sensitivity is unknown. To examine this possibility, female BALB/c and 129 mice were exposed to a single dose of 1 Gy (cesium-137 γ) TBI at 5 weeks of age, and ovarian tissue was harvested for histological and gene expression analyses 2 weeks post exposure. Sham-treated mice served as controls. 1 Gy radiation nearly eradicated the primordial follicles and dramatically decreased the primary follicles in both strains. In contrast, larger growing follicles were less affected in the 129 relative to BALB/c strain. Although this TBI paradigm did not induce detectable ovarian fibrosis in either of the strains, we did observe strain-dependent changes in osteopontin (Spp1) expression, a gene involved in wound healing, inflammation, and fibrosis. Ovaries from BALB/c mice exhibited higher baseline Spp1 expression that underwent a significant decrease in response to radiation relative to ovaries from the 129 strain. A correspondingly greater change in the ovarian matrix, as evidenced by reduced ovarian hyaluronan content, was also observed following TBI in BALB/c mice relative to 129 mice. These early changes in the ovary may predispose BALB/c mice to more pronounced late effects of TBI. Taken together, our results demonstrate that aspects of ovarian damage mirror other organ systems with respect to overall strain-dependent radiation sensitivity.

scholarly journals The Natural Carotenoid Crocetin and the Synthetic Tellurium Compound AS101 Protect the Ovary against Cyclophosphamide by Modulating SIRT1 and Mitochondrial Markers

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Giovanna Di Emidio ◽  
Giulia Rossi ◽  
Isabelle Bonomo ◽  
Gonzalo Luis Alonso ◽  
Roberta Sferra ◽  
...  
Keyword(s):  
Cell Fate ◽  
Redox Balance ◽  
Cancer Therapies ◽  
Protective Effects ◽  
Synthetic Compound ◽  
Primordial Follicles ◽  
Mitochondrial Markers ◽  
Cd1 Mice ◽  
Ovarian Damage ◽  
Cellular Defence

Cancer therapies are associated with increased infertility risk due to accelerated reproductive aging. Oxidative stress (OS) is a potential mechanism behind ovarian toxicity by cyclophosphamide (CPM), the most ovotoxic anticancer drug. An important sensor of OS is SIRT1, a NAD+-dependent deacetylase which regulates cellular defence and cell fate. This study investigated whether the natural carotenoid crocetin and the synthetic compound AS101 protect the ovary against CPM by modulating SIRT1 and mitochondrial markers. We found that the number of primordial follicles of female CD1 mice receiving crocetin plus CPM increased when compared with CPM alone and similar to AS101, whose protective effects are known. SIRT1 increased in CPM mouse ovaries revealing the occurrence of OS. Similarly, mitochondrial SIRT3 rose, whilst SOD2 and the mitochondrial biogenesis activator PGC1-α decreased, suggesting the occurrence of mitochondrial damage. Crocetin and AS101 administration prevented SIRT1 burst suggesting that preservation of redox balance can help the ovary to counteract ovarian damage by CPM. Decreased SIRT3 and increased SOD2 and PGC1-α in mice receiving crocetin or AS101 prior to CPM provide evidence for mitochondrial protection. Present results improve the knowledge of ovarian damage by CPM and may help to develop interventions for preserving fertility in cancer patients.

Serum AMH concentration has limited prognostic value for the density of primordial follicles questioning AMH as a parameter for the real ovarian reserve

2018 ◽  
Author(s):  
J Liebenthron ◽  
J Reinsberg ◽  
R Fimmers ◽  
N Sänger ◽  
K van der Ven ◽  
...  
Keyword(s):  
Ovarian Reserve ◽  
Prognostic Value ◽  
Primordial Follicles ◽  
The Real

Polymeric antibacterial systems based on passive targeting and synergistic effect

2020 ◽  
Author(s):  
◽  
Jielin Ma
Keyword(s):  
Synergistic Effect ◽  
Passive Targeting

Characteristics Of The Structure Formation Of Gypsum Binder Modified With Zinc Hydrosilicates

2020 ◽  
pp. 40-46
Keyword(s):  
Synergistic Effect ◽  
Physicochemical Properties ◽  
Structure Formation ◽  
Silicic Acid ◽  
Chemical Properties ◽  
Crystal Formation ◽  
Ability To Act ◽  
Chemical Factors ◽  
Sorption Characteristics

The authors' methodic for assessing the role of chemical and physic-chemical factors during the structure formation of gypsum stone is presented in the article. The methodic is also makes it possible to reveal the synergistic effect and to determine the ranges of variation of controls factors that ensure maximum values of such effect. The effect of a micro-sized modifier based on zinc hydro-silicates on the structure formation of building gypsum is analyzed and corresponding dependencies are found. It is shown that effects of influence of modifier on the properties of gypsum compositions are determined by chemical properties of modifier. Among the mentioned properties are sorption characteristics (which depend on the amount of silicic acid and its state) and physicochemical properties - the ability to act as a substrate during crystal formation. The proposed method can also be extended to other binding substances and materials. This article contributes to the understanding of the processes that occur during the structure formation of composites, which will make it possible to control the structure formation in the future, obtaining materials with a given set of properties.

Proceedings: Primordial follicles in the ovary of the neonatal ewe lamb

Reproduction ◽  
1976 ◽  
Vol 46 (2) ◽  
pp. 514-515 ◽  
Author(s):  
C Worthington
Keyword(s):  
Primordial Follicles ◽  
Ewe Lamb

Classification of small type B/C follicles as primordial follicles in mature rats

Reproduction ◽  
2000 ◽  
pp. 43-48 ◽  
Author(s):  
S Meredith ◽  
G Dudenhoeffer ◽  
K Jackson
Keyword(s):  
Dna Synthesis ◽  
Granulosa Cells ◽  
Single Layer ◽  
Reliable Indicator ◽  
Type B ◽  
Primordial Follicles ◽  
Type C

In the present study, follicles were classified according to the morphology of their granulosa cells. Type B follicles contained only flattened granulosa cells; type B/C follicles had a mixture of flattened and cuboidal granulosa cells in a single layer, and type C follicles had a single layer of cuboidal granulosa cells. The primary objectives of the study were to determine whether 5-bromo-2-deoxyuridine incorporation into type B/C follicles was a marker for initiation of growth and how long type B/C follicles could remain at the same stage before transformation to type C follicles. Female Holtzman rats received bromo-deoxyuridine for 7 days. After the infusion (day minipumps were removed = day 0), rats were ovariectomized on days 0 (n = 9), 30 (n = 8), 90 (n = 8) and 150 (n = 9). The numbers of type B, B/C and C follicles within one ovary were determined using modified fractionator counting. Analysis over all times demonstrated that there were more (P < 0.0001) type B/C (941 +/- 61 per ovary) than type C (140 +/- 18 per ovary) or type B (159 +/- 19 per ovary) follicles. The numbers of type B and type C follicles did not differ from each other at any time. Only one of 34 rats evaluated had bromo-deoxyuridine-labelled type B follicles. On day 150, 57% of the bromo-deoxyuridine-labelled type B/C follicles remained from day 0. It is concluded that (1) DNA synthesis in granulosa cells of type B/C follicles is not a reliable indicator of impending growth; and (2) type B and type B/C follicles are both components of the pool of primordial follicles.

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