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      The Relationship between Sperm Oxidative Stress Alterations and IVF/ICSI Outcomes: A Systematic Review from Nonhuman Mammals

      review-article
      1 , 2 , * , 1 , 2 , 3 , *
      Biology
      MDPI
      infertility, sperm, oxidative stress, ROS, DNA damage, IVF, ICSI

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          Abstract

          Achieving high embryo quality following IVF and ICSI procedures is a key factor in increasing fertility outcomes in human infertile couples. While the male factor is known to underlie infertility in about 50% of cases, studies performed in human infertile couples have not been able to define the precise effect of sperm affectations upon embryo development. This lack of consistency is, in most cases, due to the heterogeneity of the results caused by the multiple male and female factors that mask the concrete effect of a given sperm parameter. These biases can be reduced with the use of animal gametes, being a good approach for basic researchers to design more homogeneous studies analyzing the specific consequences of a certain affectation. Herein, we conducted a systematic review (March 2020) that assessed the relationship between sperm oxidative stress alterations and IVF/ICSI outcomes in nonhumans mammals. The review was conducted according to PRISMA guidelines and using the MEDLINE-PubMed and EMBASE databases. Thirty articles were included: 11 performed IVF, 17 conducted ICSI, and two carried out both fertilization methods. Most articles were conducted in mouse (43%), cattle (30%) and pig models (10%). After IVF treatments, 80% of studies observed a negative effect of sperm oxidative stress on fertilization rates, and 100% of studies observed a negative effect on blastocyst rates. After ICSI treatments, a positive relationship of sperm oxidative stress with fertilization rates (75% of studies) and with blastocyst rates (83% of studies) was found. In conclusion, the present systematic review shows that sperm oxidative stress is associated with a significant reduction in fertilization rates and in vitro embryo development.

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          Most cited references77

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          Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder.

          Increasing evidence indicates that metabolic disorders in offspring can result from the father's diet, but the mechanism remains unclear. In a paternal mouse model given a high-fat diet (HFD), we showed that a subset of sperm transfer RNA-derived small RNAs (tsRNAs), mainly from 5' transfer RNA halves and ranging in size from 30 to 34 nucleotides, exhibited changes in expression profiles and RNA modifications. Injection of sperm tsRNA fractions from HFD males into normal zygotes generated metabolic disorders in the F1 offspring and altered gene expression of metabolic pathways in early embryos and islets of F1 offspring, which was unrelated to DNA methylation at CpG-enriched regions. Hence, sperm tsRNAs represent a paternal epigenetic factor that may mediate intergenerational inheritance of diet-induced metabolic disorders.
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            The biology of infertility: research advances and clinical challenges.

            Reproduction is required for the survival of all mammalian species, and thousands of essential 'sex' genes are conserved through evolution. Basic research helps to define these genes and the mechanisms responsible for the development, function and regulation of the male and female reproductive systems. However, many infertile couples continue to be labeled with the diagnosis of idiopathic infertility or given descriptive diagnoses that do not provide a cause for their defect. For other individuals with a known etiology, effective cures are lacking, although their infertility is often bypassed with assisted reproductive technologies (ART), some accompanied by safety or ethical concerns. Certainly, progress in the field of reproduction has been realized in the twenty-first century with advances in the understanding of the regulation of fertility, with the production of over 400 mutant mouse models with a reproductive phenotype and with the promise of regenerative gonadal stem cells. Indeed, the past six years have witnessed a virtual explosion in the identification of gene mutations or polymorphisms that cause or are linked to human infertility. Translation of these findings to the clinic remains slow, however, as do new methods to diagnose and treat infertile couples. Additionally, new approaches to contraception remain elusive. Nevertheless, the basic and clinical advances in the understanding of the molecular controls of reproduction are impressive and will ultimately improve patient care.
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              Oocyte-secreted factors: regulators of cumulus cell function and oocyte quality.

              Oocyte quality is a key limiting factor in female fertility, yet we have a poor understanding of what constitutes oocyte quality or the mechanisms governing it. The ovarian follicular microenvironment and maternal signals, mediated primarily through granulosa cells (GCs) and cumulus cells (CCs), are responsible for nurturing oocyte growth, development and the gradual acquisition of oocyte developmental competence. However, oocyte-GC/CC communication is bidirectional with the oocyte secreting potent growth factors that act locally to direct the differentiation and function of CCs. Two important oocyte-secreted factors (OSFs) are growth-differentiation factor 9 and bone morphogenetic protein 15, which activate signaling pathways in CCs to regulate key genes and cellular processes required for CC differentiation and for CCs to maintain their distinctive phenotype. Hence, oocytes appear to tightly control their neighboring somatic cells, directing them to perform functions required for appropriate development of the oocyte. This oocyte-CC regulatory loop and the capacity of oocytes to regulate their own microenvironment by OSFs may constitute important components of oocyte quality. In support of this notion, it has recently been demonstrated that supplementing oocyte in vitro maturation (IVM) media with exogenous OSFs improves oocyte developmental potential, as evidenced by enhanced pre- and post-implantation embryo development. This new perspective on oocyte-CC interactions is improving our knowledge of the processes regulating oocyte quality, which is likely to have a number of applications, including improving the efficiency of clinical IVM and thereby providing new options for the treatment of infertility.
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                Author and article information

                Journal
                Biology (Basel)
                Biology (Basel)
                biology
                Biology
                MDPI
                2079-7737
                21 July 2020
                July 2020
                : 9
                : 7
                : 178
                Affiliations
                [1 ]Biotechnology of Animal and Human Reproduction (TechnoSperm), Institute of Food and Agricultural Technology, University of Girona, 17003 Girona, Spain; marc.yeste@ 123456udg.edu
                [2 ]Unit of Cell Biology, Department of Biology, Faculty of Sciences, University of Girona, 17003 Girona, Spain
                [3 ]Andrology and IVF Laboratory, Division of Urology, Department of Surgery, University of Utah School of Medicine, Salt Lake City, UT 84108, USA
                Author notes
                [* ]Correspondence: j.ribas87@ 123456gmail.com (J.R.-M.); albert.salas@ 123456utah.edu (A.S.-H.); Tel.: +34-972-419-514 (J.R.-M.); +1-(385)-210-5534 (A.S.-H.)
                Author information
                https://orcid.org/0000-0002-9101-2044
                https://orcid.org/0000-0002-2209-340X
                https://orcid.org/0000-0001-5914-6862
                Article
                biology-09-00178
                10.3390/biology9070178
                7408105
                32708086
                f54643eb-5a1d-4383-b402-317b5d1bda19
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 01 July 2020
                : 17 July 2020
                Categories
                Review

                infertility,sperm,oxidative stress,ros,dna damage,ivf,icsi
                infertility, sperm, oxidative stress, ros, dna damage, ivf, icsi

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