scholarly journals Epigallocatechin gallate and theaflavins independently alleviate cyclophosphamide-induced ovarian damage by inhibiting the overactivation of primordial follicles and follicular atresia

Phytomedicine ◽  
2021 ◽  
pp. 153752
Author(s):  
Qian Chen ◽  
Zheyuan Xu ◽  
Xiang Li ◽  
Dingfu Du ◽  
Tong Wu ◽  
...  
Keyword(s):  
Epigallocatechin Gallate ◽  
Follicular Atresia ◽  
Primordial Follicles ◽  
Ovarian Damage

scholarly journals The Attenuating Effect of the Intraovarian Bone Morphogenetic Protein 4 on Age-Related Endoplasmic Reticulum Stress in Chicken Follicular Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-17 ◽  
Author(s):  
Jinwei Yao ◽  
Yanfen Ma ◽  
Xin Lin ◽  
Shuo Zhou ◽  
Yuling Mi ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Bone Morphogenetic Protein ◽  
Egg Production ◽  
Bone Morphogenetic Protein 4 ◽  
Follicular Atresia ◽  
Primordial Follicles ◽  
Age Related ◽  
Morphogenetic Protein ◽  
Laying Performance

In the poultry, only less than 5% primordial follicles in the ovary can develop into the prehierarchical follicles (PHFs) leading to progressive development, ovulation, and egg formation. This low rate of recruitment indicates a huge potential for improvement of the laying performance. A great reduction in egg production is caused by aging with extensive follicular atresia. In this study, age-related changes in the laying performance and ovarian status were compared between the peak-lay (D280) and aged (D580) chickens. Subsequently, a cross coculture of PHFs and granulosa cells (GCs) from D280 or D580 hens was adopted to reveal the mechanism of declined follicle development. Results showed that persistent endoplasmic reticulum (ER) stress in GCs of the aged hens was accompanied with intensified apoptosis. Bone morphogenetic protein 4 (BMP4) secreted by GCs of PHFs in D280 hens was capable of relieving ER stress and improving follicular dominance for selection in D580 hens. During this action, BMP4 reduced free calreticulin (CALR, an ER marker) content and attenuated cell apoptosis in PHFs of D580 hens via the PERK-CHOP-BCL2/caspase3 or CALR-Ca2+-BCL2-caspase12 pathway. Furthermore, BMP4 prevented follicular atresia by promoting production of steroid hormones to improve survival of GCs in PHFs from the aged hens. In conclusion, intensified ER stress and apoptosis occurred in GCs of PHFs in aged chickens, while BMP4 secreted by GCs was capable of improving follicular viability by alleviating ER stress to promote follicular development.

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.

Prenatally administered dexamethasone impairs folliculogenesis in spiny mouse offspring

2016 ◽  
Vol 28 (7) ◽  
pp. 1038 ◽  
Author(s):  
Monika Hułas-Stasiak ◽  
Piotr Dobrowolski ◽  
Ewa Tomaszewska
Keyword(s):  
Caspase 3 ◽  
Follicular Development ◽  
Treated Group ◽  
Spiny Mouse ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Follicular Atresia ◽  
Dexamethasone Treatment ◽  
Primordial Follicles ◽  
Acomys Cahirinus ◽  
Active Caspase

This study was designed to determine whether prenatal dexamethasone treatment has an effect on follicular development and atresia in the ovary of spiny mouse (Acomys cahirinus) offspring. Dexamethasone (125 µg kg–1 bodyweight per day) was administered to pregnant spiny mice from Day 20 of gestation to parturition. The processes of follicle loss were analysed using classical markers of apoptosis (terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling reaction, active caspase-3) and autophagy (Lamp1). The present study indicated that dexamethasone reduced the pool of healthy primordial follicles. Moreover, the oocytes from these follicles showed intensive caspase-3 and Lamp1 staining. Surprisingly, dexamethasone caused an increase in the number of secondary follicles; however, most of these follicles were characterised by extensive degeneration of the oocyte and caspase-3 and Lamp1 labelling. Western-blot analysis indicated that the glucocorticoid receptor as well as apoptosis and autophagy markers were more strongly expressed in the DEX-treated group than in the control. On the basis of these findings, we have concluded that dexamethasone impairs spiny mouse folliculogenesis and enhances follicular atresia through induction of autophagy or combined autophagy and apoptosis.

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 Increased Oocyte Degeneration and Follicular Atresia during the Estrous Cycle in Anti-Müllerian Hormone Null Mice

Endocrinology ◽  
2007 ◽  
Vol 148 (5) ◽  
pp. 2301-2308 ◽  
Author(s):  
Jenny A. Visser ◽  
Alexandra L. L. Durlinger ◽  
Isolde J. J. Peters ◽  
Edwin R. van den Heuvel ◽  
Ursula M. Rose ◽  
...  
Keyword(s):  
Estrous Cycle ◽  
Genetic Model ◽  
Follicular Atresia ◽  
Primordial Follicles ◽  
Normal Number ◽  
Preovulatory Follicles ◽  
Major Loss ◽  
Species Specific ◽  
Specific Number ◽  
Cyclic Recruitment

Anti-Müllerian hormone (AMH) plays an important role in folliculogenesis. AMH null mice display an increased recruitment of primordial follicles. Nevertheless, these mice do not have proportionally more preovulatory follicles. Therefore, AMH null mice provide an interesting genetic model to study the regulation of species-specific number of preovulatory follicles. We studied the follicle pool throughout the estrous cycle at 4 months of age. Analysis of the follicle pool revealed that AMH null mice have an increased and earlier cyclic recruitment of growing follicles despite a blunted FSH surge at estrus. However, FSH levels at estrus were apparently too low to support growth to the preovulatory stage because an increased level of atresia was observed, which neutralized the increased cyclic recruitment. When AMH null mice were subjected to a superovulation scheme, the rise in FSH levels resulted in the rescue of the recruited cohort of growing follicles. Analysis of the follicle pool also revealed that the increased recruitment of primordial follicles in AMH null mice was neutralized by an increased loss of follicles during the transition from small preantral to large preantral follicle. This major loss of follicles was not completely reflected by a corresponding augmentation of atresia but did correspond with an increased number of oocyte remnants observed in AMH null mice. We conclude that a combination of increased oocyte degeneration and increased follicular atresia neutralizes the increased initial and cyclic recruitment in AMH null mice to a normal number of preovulatory follicles.

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.

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