Role of the mitochondrial genome in preimplantation development and assisted reproductive technologies

2005 ◽  
Vol 17 (2) ◽  
pp. 15 ◽  
Author(s):  
Lawrence C. Smith ◽  
Jacob Thundathil ◽  
France Filion

Our fascination for mitochondria relates to their origin as symbiotic, semi-independent organisms on which we, as eukaryotic beings, rely nearly exclusively to produce energy for every cell function. Therefore, it is not surprising that these organelles play an essential role in many events during early development and in artificial reproductive technologies (ARTs) applied to humans and domestic animals. However, much needs to be learned about the interactions between the nucleus and the mitochondrial genome (mtDNA), particularly with respect to the control of transcription, replication and segregation during preimplantation. Nuclear-encoded factors that control transcription and replication are expressed during preimplantation development in mice and are followed by mtDNA transcription, but these result in no change in mtDNA copy number. However, in cattle, mtDNA copy number increases during blastocyst expansion and hatching. Nuclear genes influence the mtDNA segregation patterns in heteroplasmic animals. Because many ARTs markedly modify the mtDNA content in embryos, it is essential that their application is preceded by careful experimental scrutiny, using suitable animal models.

Zygote ◽  
2015 ◽  
Vol 24 (4) ◽  
pp. 617-623 ◽  
Author(s):  
Hanne Skovsgaard Pedersen ◽  
Peter Løvendahl ◽  
Knud Larsen ◽  
Lone Bruhn Madsen ◽  
Henrik Callesen

SummaryOocyte capacity is relevant in understanding decreasing female fertility and in the use of assisted reproductive technologies in human and farm animals. Mitochondria are important to the development of a functionally good oocyte and the oocyte mtDNA copy number has been introduced as a useful parameter for prediction of oocyte competence. The aim of this study was to investigate: (i) if the oocyte donor has an influence on its oocyte's mtDNA copy number; and (ii) the relation between oocyte size and mtDNA copy number using pre- and postpubertal pig oocytes. Cumulus–oocyte complexes were collected from individual donor pigs. The oocytes were allocated into different size-groups, snap-frozen and single-oocyte mtDNA copy number was estimated by quantitative real-time PCR using the genes ND1 and COX1. Results showed that mean mtDNA copy number in oocytes from any individual donor could be categorized as either ‘high’ (≥100,000) or ‘low’ (<100,000) with no difference in threshold between pre- and postpubertal oocytes. No linear correlation was detected between oocyte size and mtDNA copy number within pre- and postpubertal oocytes. This study demonstrates the importance of the oocyte donor in relation to oocyte mtDNA copy number, irrespectively of the donor's puberty status and the oocyte's growth stage. Observations from this study facilitate both further investigations of the importance of mtDNA copy number and the unravelling of relations between different mitochondrial parameters and oocyte competence.


2021 ◽  
Vol 22 (11) ◽  
pp. 5918
Author(s):  
Paweł Kordowitzki ◽  
Gabriela Sokołowska ◽  
Marta Wasielak-Politowska ◽  
Agnieszka Skowronska ◽  
Mariusz T. Skowronski

The oocyte is the major determinant of embryo developmental competence in all mammalian species. Although fundamental advances have been generated in the field of reproductive medicine and assisted reproductive technologies in the past three decades, researchers and clinicians are still trying to elucidate molecular factors and pathways, which could be pivotal for the oocyte’s developmental competence. The cell-to-cell and cell-to-matrix communications are crucial not only for oocytes but also for multicellular organisms in general. This latter mentioned communication is among others possibly due to the Connexin and Pannexin families of large-pore forming channels. Pannexins belong to a protein group of ATP-release channels, therefore of high importance for the oocyte due to its requirements of high energy supply. An increasing body of studies on Pannexins provided evidence that these channels not only play a role during physiological processes of an oocyte but also during pathological circumstances which could lead to the development of diseases or infertility. Connexins are proteins that form membrane channels and gap-junctions, and more precisely, these proteins enable the exchange of some ions and molecules, and therefore they do play a fundamental role in the communication between the oocyte and accompanying cells. Herein, the role of Pannexins and Connexins for the processes of oogenesis, folliculogenesis, oocyte maturation and fertilization will be discussed and, at the end of this review, Pannexin and Connexin related pathologies and their impact on the developmental competence of oocytes will be provided.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sandra Monfort ◽  
Carmen Orellana ◽  
Silvestre Oltra ◽  
Mónica Rosello ◽  
Alfonso Caro-Llopis ◽  
...  

AbstractDevelopment of assisted reproductive technologies to address infertility has favored the birth of many children in the last years. The majority of children born with these treatments are healthy, but some concerns remain on the safety of these medical procedures. We have retrospectively analyzed both the fertilization method and the microarray results in all those children born between 2010 and 2019 with multiple congenital anomalies, developmental delay and/or autistic spectrum disorder (n = 486) referred for array study in our center. This analysis showed a significant excess of pathogenic copy number variants among those patients conceived after in vitro fertilization with donor oocyte with respect to those patients conceived by natural fertilization (p = 0.0001). On the other hand, no significant excess of pathogenic copy number variants was observed among patients born by autologous oocyte in vitro fertilization. Further studies are necessary to confirm these results and in order to identify the factors that may contribute to an increased risk of genomic rearrangements, as well as consider the screening for genomic alterations after oocyte donation in prenatal diagnosis.


1999 ◽  
Vol 7 (1) ◽  
pp. 41-60 ◽  
Author(s):  
Mark A Damario ◽  
Owen K Davis ◽  
Zev Rosenwaks

Age is perhaps the most important single variable influencing outcome in the assisted reproductive technologies (ART). The effect of advancing age on clinical ART outcome is manifested not only in the pattern of ovarian response to stimulation regimens, but also in reduced implantation efficiency and an increased spontaneous abortion rate. The clinical importance of these factors is compounded by the fact that increasing numbers of older women are presenting for ART treatment. Delayed childbearing is becoming increasingly common in the western world. The availability of methods of birth control, educational and career priorities for women, and the increased rates of divorce and remarriage are some of the factors contributing to this phenomenon.


2021 ◽  
pp. 70-76
Author(s):  
Abuduwaili Ruziguli ◽  
Nikolai Nikolaevich Rukhliada ◽  
Anna Nikolaevna Taits ◽  
Tatyana Ivanovna Prohorovich ◽  
Tatyana Aleksandrovna Libova

This article is devoted to the assessment of the role of ALK5 in the profile of early reproductive losses in the use of assisted reproductive technologies, in particular, by using immunohistochemical study in the group of patients with early spontaneous abortion after the procedure of embryo transfer, a lower level of ALK5 expression in the decidual tissue was revealed (in comparison with control), which may be related to the occurrence of early reproductive losses caused by the imbalance in Th1 / Th2 and its effect on the increase in the concentration of natural killer cells.


2020 ◽  
Author(s):  
Zuriñe Antón ◽  
Grace Mullally ◽  
Holly Ford ◽  
Marc W. van der Kamp ◽  
Mark D. Szczelkun ◽  
...  

ABSTRACTCurrent methodologies for targeting the mitochondrial genome for basic research and/or therapeutic strategy development in mitochondrial diseases are restricted by practical limitations and technical inflexibility. The development of a functional molecular toolbox for CRISPR-mediated mitochondrial genome editing is therefore desirable, as this could enable precise targeting of mtDNA haplotypes using the precision and tuneability of CRISPR enzymes; however, published reports of “MitoCRISPR” systems have, to date, lacked reproducibility and independent corroboration. Here, we have explored the requirements for a functional MitoCRISPR system in human cells by engineering several versions of CRISPR nucleases, including the use of alternative mitochondrial protein targeting sequences and smaller paralogues, and the application of gRNA modifications that reportedly induce mitochondrial import. We demonstrate varied mitochondrial targeting efficiencies and influences on mitochondrial dynamics/function of different CRISPR nucleases, with Lachnospiraceae bacterium ND2006 (Lb) Cas12a being better targeted and tolerated than Cas9 variants. We also provide evidence of Cas9 gRNA association with mitochondria in HeLa cells and isolated yeast mitochondria, even in the absence of a targeting RNA aptamer. Finally, we present evidence linking mitochondrial-targeted LbCas12a/crRNA with increased mtDNA copy number dependent upon DNA binding and cleavage activity. We discuss reproducibility issues and the future steps necessary if MitoCRISPR is to be realised.


1998 ◽  
Vol 70 (2) ◽  
pp. 378-380 ◽  
Author(s):  
Giovanni B La Sala ◽  
Rossella Montanari ◽  
Luisella Dessanti ◽  
Corrado Cigarini ◽  
Fabrizio Sartori

Genes ◽  
2019 ◽  
Vol 10 (12) ◽  
pp. 1009 ◽  
Author(s):  
Saqib Umer ◽  
Shan Jiang Zhao ◽  
Abdul Sammad ◽  
Bahlibi Weldegebriall Sahlu ◽  
YunWei Pang ◽  
...  

Anti-Müllerian hormone (AMH) is a reliable and easily detectable reproductive marker for the fertility competence of many farm animal species. AMH is also a good predictor of superovulation in cattle, sheep, and mares. In this review, we have summarized the recent findings related to AMH and its predictive reliability related to fertility and superovulation in domestic animals, especially in cattle. We focused on: (1) the dynamics of AMH level from infancy to prepubescence as well as during puberty and adulthood; (2) AMH as a predictor of fertility; (3) the association between antral follicle count (AFC) and plasma AMH level; (4) AMH as a predictor of superovulation; and (5) factors affecting AMH levels in domestic animals, especially cattle. Many factors affect the circulatory levels of AMH when considering the plasma, like nutrition, activity of granulosa cells, disease state and endocrine disruptions during fetal life. Briefly, we concluded that AMH concentrations are static within individuals, and collection of a single dose of blood has become more popular in the field of assisted reproductive technologies (ART). It may act as a potential predictor of fertility, superovulation, and ovarian disorders in domestic animals. However, due to the limited research in domestic animals, this potential of AMH remains underutilized.


2020 ◽  
Vol 9 (2) ◽  
pp. 12 ◽  
Author(s):  
Rossella Tomaiuolo ◽  
Iolanda Veneruso ◽  
Federica Cariati ◽  
Valeria D’Argenio

During the last decade, the availability of next-generation sequencing-based approaches has revealed the presence of microbial communities in almost all the human body, including the reproductive tract. As for other body sites, this resident microbiota has been involved in the maintenance of a healthy status. As a consequence, alterations due to internal or external factors may lead to microbial dysbiosis and to the development of pathologies. Female reproductive microbiota has also been suggested to affect infertility, and it may play a key role in the success of assisted reproductive technologies, such as embryo implantation and pregnancy care. While the vaginal microbiota is well described, the uterine microbiota is underexplored. This could be due to technical issues, as the uterus is a low biomass environment. Here, we review the state of the art regarding the role of the female reproductive system microbiota in women’s health and human reproduction, highlighting its contribution to infertility.


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