scholarly journals Ceramide and mitochondrial function in aging oocytes: joggling a new hypothesis and old players

Reproduction ◽  
2012 ◽  
Vol 143 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Loro L Kujjo ◽  
Gloria I Perez

Maternal aging adversely affects oocyte quality (function and developmental potential) and consequently lowers pregnancy rates while increasing spontaneous abortions. Substantial evidence, especially from egg donation studies, implicates the decreased quality of an aging oocyte as a major factor in the etiology of female infertility. Nevertheless, the cellular and molecular mechanisms responsible for the decreased oocyte quality with advanced maternal aging are not fully characterized. Herein we present information in the published literature and our own data to support the hypothesis that during aging induced decreases in mitochondrial ceramide levels and associated alterations in mitochondrial structure and function are prominent elements contributing to reduced oocyte quality. Hence, by examining the molecular determinants that underlie impairments in oocyte mitochondria, we expect to sieve to a better understanding of the mechanistic anatomy of oocyte aging.

Author(s):  
Eugene Matthew P. Almazan ◽  
Joseph F. Ryan ◽  
Labib Rouhana

Detection of chemical stimuli is crucial for living systems and also contributes to quality of life in humans. Since loss of olfaction becomes more prevalent with aging, longer life expectancies have fueled interest in understanding the molecular mechanisms behind the development and maintenance of chemical sensing. Planarian flatworms possess an unsurpassed ability for stem cell-driven regeneration that allows them to restore any damaged or removed part of their bodies. This includes anteriorly-positioned lateral flaps known as auricles, which have long been thought to play a central role in chemotaxis. The contribution of auricles to the detection of positive chemical stimuli was tested in this study using Girardia dorotocephala, a North American planarian species known for its morphologically prominent auricles. Behavioral experiments staged under laboratory conditions revealed that removal of auricles by amputation leads to a significant decrease in the ability of planarians to find food. However, full chemotactic capacity is observed as early as 2 days post-amputation, which is days prior from restoration of auricle morphology, but correlative with accumulation of ciliated cells in the position of auricle regeneration. Planarians subjected to x-ray irradiation prior to auricle amputation were unable to restore auricle morphology, but were still able to restore chemotactic capacity. These results indicate that although regeneration of auricle morphology requires stem cells, some restoration of chemotactic ability can still be achieved in the absence of normal auricle morphology, corroborating with the initial observation that chemotactic success is reestablished 2-days post-amputation in our assays. Transcriptome profiles of excised auricles were obtained to facilitate molecular characterization of these structures, as well as the identification of genes that contribute to chemotaxis and auricle development. A significant overlap was found between genes with preferential expression in auricles of G. dorotocephala and genes with reduced expression upon SoxB1 knockdown in Schmidtea mediterranea, suggesting that SoxB1 has a conserved role in regulating auricle development and function. Models that distinguish between possible contributions to chemotactic behavior obtained from cellular composition, as compared to anatomical morphology of the auricles, are discussed.


Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 273
Author(s):  
Mara Simopoulou ◽  
Anna Rapani ◽  
Sokratis Grigoriadis ◽  
Agni Pantou ◽  
Petroula Tsioulou ◽  
...  

Endometriosis-related infertility describes a case of deteriorated fecundity when endometriosis is diagnosed. Numerous mechanisms have been proposed in an effort to delineate the multifaceted pathophysiology that induces impairment of reproductive dynamics in patients with endometriosis. In this critical analysis, authors present the plethora of molecular events that are entailed and elaborate on how they potentially impair the oocyte’s and embryo’s competence in patients with endometriosis. Reactive oxygen species, dysregulation of the immune system and cellular architectural disruption constitute the crucial mechanisms that detrimentally affect oocyte and embryo developmental potential. The molecular level impairment of the reproductive tissue is discussed, since differentiation, proliferation and apoptosis constitute focal regulatory cellular functions that appear severely compromised in cases of endometriosis. Mapping the precise molecular mechanisms entailed in endometriosis-related infertility may help delineate the complex nature of the disorder and bring us a step closer to a more personalized approach in understanding, diagnosing and managing endometriosis-related infertility.


Reproduction ◽  
2018 ◽  
Vol 156 (1) ◽  
pp. 81-92 ◽  
Author(s):  
Qingling Yang ◽  
Shanjun Dai ◽  
Xiaoyan Luo ◽  
Jing Zhu ◽  
Fangyuan Li ◽  
...  

The quality of postovulatory metaphase II oocytes undergoes a time-dependent deterioration as a result of the aging process. Melatonin is considered to be an anti-aging agent. However, the underlying mechanisms of how melatonin improves the quality of postovulatory aged oocytes remain largely unclear. In this study, by using mouse model, we found that there were elevated reactive oxygen species levels and impaired mitochondrial function demonstrated by reduced mitochondrial membrane potential and increased mitochondrial aggregation in oocytes aged 24 h, accompanied by an increased number of meiotic errors, unregulated autophagy-related proteins and early apoptosis, which led to decreased oocyte quality and disrupted developmental competence. However, all of these events can be largely prevented by supplementing the oocyte culture medium with 10−3 M melatonin. Additionally, we found that the expression of sirtuin family members (SIRT1, 2 and 3) was dramatically reduced in aged oocytes. In addition,in vitrosupplementation with melatonin significantly upregulated the expression of SIRT1 and antioxidant enzyme MnSOD, but this action was not observed for SIRT2 and SIRT3. Furthermore, the protective effect of melatonin on the delay of oocyte aging vanished when the SIRT1 inhibitor EX527 was used to simultaneously treat the oocytes with melatonin. Consistent with this finding, we found that the postovulatory oocyte aging process was markedly attenuated when the oocytes were treated with the SIRT1 activator SRT1720. In conclusion, our data strongly indicate that melatonin delays postovulatory mouse oocyte aging via a SIRT1–MnSOD-dependent pathway, which may provide a molecular mechanism support for the further application of melatonin in the assisted reproductive technology field.


Author(s):  
Rachel T. Cox ◽  
Joanna Poulton ◽  
Suzannah Alice Williams

There is a worldwide trend for women to have their first pregnancy later in life. However, as oocyte quality declines with maternal aging, this trend leads to an increase in subfertility. The cellular mechanisms underlying this decline in oocyte competence are poorly understood. Oocyte mitochondria are the subcellular organelles that supply the energy that drives early embryogenesis, and thus their quality is critical for successful conception. Mitochondria contain their own DNA (mtDNA) and mutations in mtDNA cause mitochondrial diseases with severe symptoms, such as neurodegeneration and heart disease. Since mitochondrial function declines in tissues as humans age accompanied by an accumulation of mtDNA mutations, mtDNA is implicated as a cause of declining oocyte quality in older mothers. While this mutation load could be caused by declining accuracy of the mitochondrial replisome, age-related decline in mitochondrial quality control likely contributes however knowledge is lacking. Mitophagy, a cellular process which specifically targets and recycles damaged mitochondria, may be involved, but studies are scarce. And although assisted reproductive technologies (ART) can help older mothers, how these techniques affect the mechanisms that regulate mitochondrial and oocyte quality have not been studied. With the long-term goal of understanding the molecular mechanisms that control mitochondrial quality in the oocyte, model systems including Drosophila and mouse as well as human oocytes have been used. In this review we explore the contribution of mitophagy to oocyte quality and the need for further systematic investigation in oocytes during maternal aging using different systems.


2020 ◽  
Vol 32 (3) ◽  
pp. 292 ◽  
Author(s):  
Saeideh Hasani Azami ◽  
Hamid Nazarian ◽  
Mohammad Amin Abdollahifar ◽  
Fatemeh Eini ◽  
Mehdi Allahbakhshian Farsani ◽  
...  

Reproductive senescence is accompanied by a reduced number and quality of ovarian follicles in response to the accumulation of free radicals and the process of apoptosis. Having selected mice as models, we examined the hypothesis that curcumin as an antioxidant and anti-inflammatory agent might prevent or retard ovarian aging. Female NMRI 21-day-old mice were divided into control, vehicle and curcumin groups. In the treatment group the mice received curcumin at 100mgkg–1day–1 intraperitoneally. After 6, 12 and 33 weeks several parameters were examined including ovarian reserve, oocyte quality, oxidative status, invitro fertilisation and expression of ovulation-related (growth differentiation factor 9 (GDF-9) and bone morphogenetic protein 15 (BMP-15)) and anti-aging-related (sirtuin 1 (SIRT-1) and SIRT-3) genes. Curcumin treatment up to 12 and 33 weeks resulted in increased ovarian volume and number of follicles and was associated with elevated anti-Müllerian hormone and oestrogen and diminished FSH serum levels. Furthermore, enhanced oocyte maturation, fertilisation and embryo development plus reduced oxidative stress were seen in the curcumin group. Also, the expression of GDF-9, BMP-15, SIRT-1 and SIRT-3 genes was increased in the curcumin group. Concerning gestational age, the findings of the study suggested that administration of curcumin could delay the process of oocyte aging in a mouse model.


2017 ◽  
Vol 29 (4) ◽  
pp. 759 ◽  
Author(s):  
Shun Takeo ◽  
Koji Kimura ◽  
Koumei Shirasuna ◽  
Takehito Kuwayama ◽  
Hisataka Iwata

Maternal age affects the quality of oocytes. The present study examined whether follicular fluid (FF) is a casual factor for age-associated decline in oocyte quality. First, we measured the concentration of advanced glycation end-products (AGE) in FF derived from young (21–45 months; Young-FF) and aged (≥120 months; Aged-FF) cows and found significantly higher concentrations of AGE in Aged-FF than Young-FF. Second, oocytes were collected from ovaries of young or aged cows and cultured in maturation medium containing 10% FF derived from young or aged cows. Regardless of oocyte origin, Aged-FF accelerated nuclear maturation progression and gap junction closure between oocytes and cumulus cells, increased reactive oxygen species (ROS) content and the rate of abnormal fertilisation of oocytes and decreased blastulation rate compared with Young-FF. Furthermore, supplementation of maturation medium with AGE induced similar age-associated events in oocytes derived from young cows, in that AGE accelerated the progression of nuclear maturation, increased ROS content in oocytes, increased the rate of abnormal fertilisation and decreased blastulation rate. In conclusion, maternal aging increased the concentration of AGE in FF, and both AGE and Aged-FF accelerated nuclear maturation and reduced the developmental competence of oocytes.


2021 ◽  
Vol 14 ◽  
Author(s):  
Xupeng Xing ◽  
Jinjing Zhang ◽  
Jingcheng Zhang ◽  
Yongsheng Wang ◽  
Jingyi Wang ◽  
...  

Background: High-quality of the oocyte is crucial for embryo development and the success of human assisted reproduction. The postovulatory aged oocytes lose the developmental competence with mitochondrial dysfunction and oxidative stress. Coenzyme Q10 (CoQ10) is widely distributed in the membranes of cells, and has an important role in the mitochondrial respiration chain, against oxidative stress and modulation of gene expression. Objective: To investigate the functions and mechanisms of CoQ10 on delaying postovulatory oocyte aging. Methods: Quantitative real-time PCR and Immunofluorescence staining were used to determine the expression patterns of the biogenesis genes of CoQ10 in postovulatory aged oocytes compared with fresh oocytes. The mitochondrial function, apoptosis, reactive oxygen species (ROS) accumulation and spindle abnormalities were investigated after treatment with 10 μM CoQ10 in aged groups. SIRT4 siRNA or capped RNA was injected into oocytes to investigate the function of SIRT4 on postovulatory oocyte aging and the relationship between CoQ10 and SIRT4. Results: Multiple CoQ10 biosynthesis enzymes are insufficient, and supplement of CoQ10 can improve oocyte quality and elevate the development competency of postovulatory aged oocytes. CoQ10 can attenuate the aging-induced abnormalities including mitochondrial dysfunction, ROS accumulation, spindle abnormalities, and apoptosis in postovulatory aged oocytes. Furthermore, SIRT4, which was first found to be up-regulated in postovulatory aged oocytes, decreased following CoQ10 treatment. Finally, knockdown of SIRT4 can rescue aging-induced dysfunction of mitochondria, and the efficiency of CoQ10 rescuing dysfunction of mitochondria can be weakened by SIRT4 overexpression. Conclusion: Supplement of CoQ10 protects oocytes from postovulatory aging by inhibiting SIRT4increase.


2020 ◽  
Vol 5 (6) ◽  
pp. 1469-1481 ◽  
Author(s):  
Joseph A. Napoli ◽  
Carrie E. Zimmerman ◽  
Linda D. Vallino

Purpose Craniofacial anomalies (CFA) often result in growth abnormalities of the facial skeleton adversely affecting function and appearance. The functional problems caused by the structural anomalies include upper airway obstruction, speech abnormalities, feeding difficulty, hearing deficits, dental/occlusal defects, and cognitive and psychosocial impairment. Managing disorders of the craniofacial skeleton has been improved by the technique known as distraction osteogenesis (DO). In DO, new bone growth is stimulated allowing bones to be lengthened without need for bone graft. The purpose of this clinical focus article is to describe the technique and clinical applications and outcomes of DO in CFA. Conclusion Distraction can be applied to various regions of the craniofacial skeleton to correct structure and function. The benefits of this procedure include improved airway, feeding, occlusion, speech, and appearance, resulting in a better quality of life for patients with CFA.


2016 ◽  
Vol 1 (13) ◽  
pp. 162-168
Author(s):  
Pippa Hales ◽  
Corinne Mossey-Gaston

Lung cancer is one of the most commonly diagnosed cancers across Northern America and Europe. Treatment options offered are dependent on the type of cancer, the location of the tumor, the staging, and the overall health of the person. When surgery for lung cancer is offered, difficulty swallowing is a potential complication that can have several influencing factors. Surgical interaction with the recurrent laryngeal nerve (RLN) can lead to unilateral vocal cord palsy, altering swallow function and safety. Understanding whether the RLN has been preserved, damaged, or sacrificed is integral to understanding the effect on the swallow and the subsequent treatment options available. There is also the risk of post-surgical reduction of physiological reserve, which can reduce the strength and function of the swallow in addition to any surgery specific complications. As lung cancer has a limited prognosis, the clinician must also factor in the palliative phase, as this can further increase the burden of an already compromised swallow. By understanding the surgery and the implications this may have for the swallow, there is the potential to reduce the impact of post-surgical complications and so improve quality of life (QOL) for people with lung cancer.


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