scholarly journals Maternal mRNA deadenylation is defective in in vitro matured mouse and human oocytes

2021 ◽  
Author(s):  
Yusheng Liu ◽  
Wenrong Tao ◽  
Yiwei Zhang ◽  
Hu Nie ◽  
Zhenzhen Hou ◽  
...  

Oocyte in vitro maturation is a technique of assisted reproductive technology that was first introduced in patients with polycystic ovarian syndrome and is now used in most fertility clinics. Thousands of genes show abnormally high expression in in vitro maturated metaphase II (in vitro MII) oocytes compared with in vivo maturated metaphase II (in vivo MII) oocytes in bovines, mice, and humans. However, the underlying mechanisms of this abnormal expression are still poorly understood. In this study, we use PAIso-seq1 to reveal a transcriptome-wide expression profile of full-length transcripts containing entire poly(A) tails in in vivo and in vitro matured mouse and human oocytes. Our results indicate that more genes are up-regulated than down-regulated in in vitro MII oocytes in both mice and humans. Furthermore, we demonstrate that the observed increase in maternal mRNA abundance is caused by impaired deadenylation in in vitro MII oocytes in both mice and humans. We also found that the cytoplasmic polyadenylation of dormant Btg4 and Cnot7 mRNAs, which encode key components of deadenylation machinery, is impaired in in vitro MII oocytes in mice and humans respectively, likely contributing to reduced translation and impaired global maternal mRNA deadenylation. Our findings highlight that impaired maternal mRNA deadenylation is a definite molecular defect in in vitro MII oocytes in both mice and humans. The findings here offer a new criterion for evaluating the quality of in vitro MII oocytes and a potential direction for improving in vitro maturation by fixing the dysregulated maternal mRNA deadenylation.

2008 ◽  
Vol 23 (5) ◽  
pp. 1138-1144 ◽  
Author(s):  
Gayle M. Jones ◽  
David S. Cram ◽  
Bi Song ◽  
M. Cristina Magli ◽  
Luca Gianaroli ◽  
...  

Zygote ◽  
1996 ◽  
Vol 4 (04) ◽  
pp. 343-348 ◽  
Author(s):  
S. Ledda ◽  
L. Bogliolo ◽  
G. Leoni ◽  
P. Calvia ◽  
S. Naitana

Much effort has been focused on establishing optimal conditions for obtainingin vitromaturation of oocytes from different species with results comparable to those achieved afterin vivodevelopment (reviewed by Brackett, 1992). However, even though extraordinary progress has been made, thein vitrotechnology for oocyte maturation lags far behind thatin vivoand improvements are needed to increase the quantity and quality of the embryos produced from these matured oocytes.


2019 ◽  
Vol 48 (1) ◽  
pp. 190-201 ◽  
Author(s):  
Sandy Eldridge ◽  
Liang Guo ◽  
John Hamre

Chemotherapy-induced peripheral neuropathy (CIPN) is an adverse effect caused by several classes of widely used anticancer therapeutics. Chemotherapy-induced peripheral neuropathy frequently leads to dose reduction or discontinuation of chemotherapy regimens, and CIPN symptoms can persist long after completion of chemotherapy and severely diminish the quality of life of patients. Differences in the clinical presentation of CIPN by widely diverse classifications of anticancer agents have spawned multiple mechanistic hypotheses that seek to explain the pathogenesis of CIPN. Despite its clinical relevance, common occurrence, and extensive investigation, the pathophysiology of CIPN remains unclear. Furthermore, there is no unequivocal gold standard for the prevention and treatment of CIPN. Herein, we review in vivo and in vitro models of CIPN with a focus on histopathological changes and morphological features aimed at understanding the pathophysiology of CIPN and identify gaps requiring deeper exploration. An elucidation of the underlying mechanisms of CIPN is imperative to identify potential targets and approaches for prevention and treatment.


2016 ◽  
Vol 28 (2) ◽  
pp. 256
Author(s):  
M. A. Sirard

Making an oocyte with the capacity to form a Day-7 embryo that will implant and produce a live healthy calf is a long and complex process. Since the beginning of bovine IVF, it has been clear that the follicle from which an oocyte is obtained is the most important factor to predict outcome. The blastocyst rate is above 75% with in vivo-matured oocytes, but success varies greatly following in vitro maturation, depending more on follicular status than size. Indeed, aspirating oocytes from non-preovulatory follicles can result in 30% blastocyst development following fertilization but rarely more, unless the follicle is selected. Follicles leading to improved development are either early atretic or exposed to FSH withdrawal. If no exogenous FSH is given, natural early atresia will occur the day after the dominant follicle is selected, but will be limited to a few follicles per wave. If FSH is given to generate a wave of dominant follicles, and then withdrawn, most of the follicles will continue growth and differentiation under basal LH and a maximal oocyte quality will be reached between Day 2 and 3 after the last FSH injection. Under these conditions, the oocyte has the right cascade of signaling to condense its chromatin and to prepare for fertilization. Oocytes obtained from less-prepared follicles are of lower quality, as demonstrated by lower blastocyst rates, lower blastocyst quality, lower implantation rates, and higher abortion rates. Genomic analysis of embryos generated from slaughterhouse-derived oocytes indicates a progressive dysfunction in direct link with the in vitro exposure time. The best way to minimize in vitro-related stress is to begin with a competent oocyte and the best demonstration of that is when some animals (treated with FSH and then coasted) generate 100% blastocyst rate for a recovery of more than 5 oocytes, indicating that the initial quality of oocytes is not much affected by the in vitro culture. It is surprising that blastocyst rates following coasting and in vitro maturation can surpass that observed with Day-7 embryo collections based on the number of ovulations. Finally, new epigenetic analysis will progressively unravel differences of oocytes obtained from different sources and will become an important research tool to assess follicular conditions that will lead to minimal culture stress and optimal embryo quality. If epigenetic programming of the embryo depends on its capacity to deal with the stress created by culture, as has been shown in other species, the initial quality of the oocyte will potentially impact the health status of the newborn calf and resulting adult.


2005 ◽  
Vol 17 (9) ◽  
pp. 69
Author(s):  
M. Lane ◽  
C. Yeo ◽  
K. S. Cashman ◽  
H. M. Hamilton

Superovulation protocols used in IVF result in multiple eggs that can be fertilized and grown in the laboratory to allow for selection of the best embryo for return to the mother, thereby increasing the chances for a successful pregnancy. However, there are many side effects of these superovulation drug protocols, such as deep vein thrombosis and hyperstimulation. The latter is of particular concern for women with polycystic ovary syndrome. Furthermore, the use of gonadotrophins has been reported to compromise both oocyte quality and the uterine environment and may contribute to the low success rates of IVF. Therefore the ability to collect large numbers of oocytes from women and mature them in vitro is an attractive alternative. However, although there are reports in the literature on extended maturation/culture periods of human oocytes the pregnancy rates are significantly lower than that observed after in vivo maturation. The ability to offer such technology is currently limited by the lack of understanding of how the conditions for in vitro maturation affect the quality of the oocyte and the resulting embryo. Our research is concentrated on establishing the role of metabolic balance in the oocyte for the maintenance of subsequent viability. We have determined that disruptions to the balance between mitochondrial and cytoplasmic metabolism in animal oocytes have significant adverse consequences for the resultant embryo. Changing conditions for in vitro maturation were also found to alter the establishment of the metabolic settings of the oocyte. The ability to determine the role of such parameters in maturing human oocytes will be important for the prospect of adoption of this technology for routine clinical practice.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
D Nikiforov ◽  
S E Pors ◽  
J Cadena. Moreno ◽  
C Ydin. Andersen

Abstract Study question Based on published studies, how effective is in vitro maturation (IVM) in different patient groups, and how does the maturation rate correlate with culture conditions? Summary answer Clinical IVM is most effective when patients receive only hCG trigger prior to oocyte collection. Multiple additional parameters influencing the outcome were identified. What is known already Despite being used for more than fifty years, the overall efficacy of human IVM has not yet been determined, and results are often conflicting. Indeed, IVM is still perceived skeptically by many embryologists and doctors and not widely used in clinical practice. This review aims to collect all available data in the literature regarding the efficacy of IVM analyzing characteristics of patients, treatment, or laboratory conditions that may influence the MII-rate (MR). Study design, size, duration: A systematic search was performed in the PubMed database following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search was limited to studies in the English language published before October 2020 using the following keyword: “oocyte in vitro maturation». Participants/materials, setting, methods Inclusion criteria for studies were: reporting data obtained on immature human oocytes, which transitioned to the MII stage after IVM. The requirement was that the numbers of cultured and matured oocytes were reported. If available, additional data were collected including patients’ characteristics (for example PCOS), hormonal stimulation prior to the procedure (administration of some FSH or hCG trigger or both), oocyte freezing before or after IVM, type of culture medium and supplements, etc. Main results and the role of chance A total of 350 publications were selected from 6866 search results, 436 abstracts, and 422 full read articles. Selected studies cover 21153 patients and 157420 immature oocytes cultured. It has been demonstrated that oocytes collected in vivo from adult, non-PCOS patients, who received only hCG trigger prior to the procedure had a statistically higher MII rate (66%) than oocytes from patients who received no gonadotropins or some FSH, or a combination of some FSH and hCG trigger (59%, 60% and 58% respectively). The same was valid for PCOS patients: MR in the trigger only cohort (66%) was significantly different from other cohorts. MR for in vivo collected oocytes (61%) from adult non-PCOS patients was significantly different from ex vivo collected oocytes (33%). MI stage oocytes at the moment of collection matured with a statistically higher rate (N = 4322, 73%), than GV oocytes (N = 3328, 54%). When in vitro matured oocytes were vitrified, their average survival rate was 81% (data from 50 studies on 1701 oocytes). Additionally, immature oocytes survived vitrification with a 75% rate (data from 30 studies on 4457 oocytes). Overall, ICSI fertilization rate for IVM oocytes was 69% (N = 59914). A total of 747 babies born from IVM were reported. Limitations, reasons for caution Among selected publications only 2 were randomized controlled trials and therefore the main challenge of this review is striking differences in setups among included studies. However, despite not being a meta-analysis, this study calculated MR for the most frequent treatment modalities and additional individual factors, which might influence MR. Wider implications of the findings: This review provides data regarding IVM efficiency in different cohorts of patients, performed under different culture conditions. Additional laboratory parameters influencing MR have been identified. Based on this new data, target groups benefiting the most were identified, and prognosis regarding the success of their treatment with IVM might be estimated. Trial registration number n/a


2019 ◽  
Vol 24 (39) ◽  
pp. 4626-4638 ◽  
Author(s):  
Reyhaneh Moradi-Marjaneh ◽  
Seyed M. Hassanian ◽  
Farzad Rahmani ◽  
Seyed H. Aghaee-Bakhtiari ◽  
Amir Avan ◽  
...  

Background: Colorectal cancer (CRC) is one of the most common causes of cancer-associated mortality in the world. Anti-tumor effect of curcumin has been shown in different cancers; however, the therapeutic potential of novel phytosomal curcumin, as well as the underlying molecular mechanism in CRC, has not yet been explored. Methods: The anti-proliferative, anti-migratory and apoptotic activity of phytosomal curcumin in CT26 cells was assessed by MTT assay, wound healing assay and Flow cytometry, respectively. Phytosomal curcumin was also tested for its in-vivo activity in a xenograft mouse model of CRC. In addition, oxidant/antioxidant activity was examined by DCFH-DA assay in vitro, measurement of malondialdehyde (MDA), Thiol and superoxidedismutase (SOD) and catalase (CAT) activity and also evaluation of expression levels of Nrf2 and GCLM by qRT-PCR in tumor tissues. In addition, the effect of phytosomal curcumin on angiogenesis was assessed by the measurement of VEGF-A and VEGFR-1 and VEGF signaling regulatory microRNAs (miRNAs) in tumor tissue. Results: Phytosomal curcumin exerts anti-proliferative, anti-migratory and apoptotic activity in-vitro. It also decreases tumor growth and augmented 5-fluorouracil (5-FU) anti-tumor effect in-vivo. In addition, our data showed that induction of oxidative stress and inhibition of angiogenesis through modulation of VEGF signaling regulatory miRNAs might be underlying mechanisms by which phytosomal curcumin exerted its antitumor effect. Conclusion: Our data confirmed this notion that phytosomal curcumin administrates anticancer effects and can be used as a complementary treatment in clinical settings.


2018 ◽  
Vol 18 (2) ◽  
pp. 156-165 ◽  
Author(s):  
Jiaqiang Wang ◽  
Chien-shan Cheng ◽  
Yan Lu ◽  
Xiaowei Ding ◽  
Minmin Zhu ◽  
...  

Background: Propofol, a widely used intravenous anesthetic agent, is traditionally applied for sedation and general anesthesia. Explanation: Recent attention has been drawn to explore the effect and mechanisms of propofol against cancer progression in vitro and in vivo. Specifically, the proliferation-inhibiting and apoptosis-inducing properties of propofol in cancer have been studied. However, the underlying mechanisms remain unclear. Conclusion: This review focused on the findings within the past ten years and aimed to provide a general overview of propofol's malignance-modulating properties and the potential molecular mechanisms.


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