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      Basic and clinical genetic studies on male infertility in Iran during 2000-2016: A review

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          Abstract

          The male factor contributes to 50% of infertility. The cause of male infertility is idiopathic and could be congenital or acquired. Among different factors which are involved in idiopathic male infertility, genetic factors are the most prevalent causes of the disease. Considering, the high prevalence of male infertility in Iran and the importance of genetic factors in the accession of it, in this article we reviewed the various studies which have been published during the last 17 yr on the genetic basis of male infertility in Iran. To do this, the PubMed and Scientific information database (SID) were regarded for the most relevant papers published in the last 17 yr referring to the genetics of male factor infertility using the keywords ‘‘genetics’’, “cytogenetic”, ‘‘male infertility”, and “Iranian population”. Literatures showed that among the Iranian infertile men Yq microdeletion and chromosomal aberrations are two main factors that intervene in the genetics of male infertility. Also, protamine deficiency (especially P2) is shown to have an influence on fertilization rate and pregnancy outcomes. The highest rate of sperm DNA damages has been found among the asthenospermia patients. In several papers, the relation between other important factors such as single gene mutations and polymorphisms with male infertility has also been reported. Recognition of the genetic factors that influence the fertility of Iranian men will shed light on the creation of guidelines for the diagnosis, consultation, and treatment of the patients."

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          Most cited references122

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          On the possible origins of DNA damage in human spermatozoa.

          DNA damage in the male germ line has been linked with a variety of adverse clinical outcomes including impaired fertility, an increased incidence of miscarriage and an enhanced risk of disease in the offspring. The origins of this DNA damage could, in principle, involve: (i) abortive apoptosis initiated post meiotically when the ability to drive this process to completion is in decline (ii) unresolved strand breaks created during spermiogenesis to relieve the torsional stresses associated with chromatin remodelling and (iii) oxidative stress. In this article, we present a two-step hypothesis for the origins of DNA damage in human spermatozoa that highlights the significance of oxidative stress acting on vulnerable, poorly protaminated cells generated as a result of defective spermiogenesis. We further propose that these defective cells are characterized by several hallmarks of 'dysmaturity' including the retention of excess residual cytoplasm, persistent nuclear histones, poor zona binding and disrupted chaperone content. The oxidative stress experienced by these cells may originate from infiltrating leukocytes or, possibly, the entry of spermatozoa into an apoptosis-like cascade characterized by the mitochondrial generation of reactive oxygen species. This oxidative stress may be exacerbated by a decline in local antioxidant protection, particularly during epididymal maturation. Finally, if oxidative stress is a major cause of sperm DNA damage then antioxidants should have an important therapeutic role to play in the clinical management of male infertility. Carefully controlled studies are now needed to critically examine this possibility.
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            The genetic causes of male factor infertility: a review.

            To illustrate the necessity for an enhanced understanding of the genetic basis of male factor infertility, to present a comprehensive synopsis of these genetic elements, and to review techniques being utilized to produce new insights in fertility research. Male factor infertility is a complex disorder that affects a large sector of the population; however, many of its etiologies are unknown. By elucidating the underlying genetic basis of infertile phenotypes, it may be possible to discover the causes of infertility and determine effective treatments for patients. The PubMed database was consulted for the most relevant papers published in the last 3 years pertaining to male factor infertility using the keywords "genetics" and "male infertility." Advances have been made in the characterization of the roles of specific genes, but further research is necessary before these results can be used as guidelines for diagnosing and treating male factor infertility. The accurate transmission of epigenetic information also has considerable influence on fertility in males and on the fertility of their offspring. Analysis of the genetic factors that impact male factor infertility will provide valuable insights into the creation of targeted treatments for patients and the determination of the causes of idiopathic infertility. Novel technologies that analyze the influence of genetics from a global perspective may lead to further developments in the understanding of the etiology of male factor infertility through the identification of specific infertile phenotype signatures. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
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              Integration of the extranuclear and nuclear actions of estrogen.

              Estrogen receptors (ERs) are localized to many sites within the cell, potentially contributing to overall estrogen action. In the nucleus, estrogen mainly modulates gene transcription, and the resulting protein products determine the cell biological actions of the sex steroid. In addition, a small pool of ERs localize to the plasma membrane and signal mainly though coupling, directly or indirectly, to G proteins. In response to steroid, signal transduction modulates both nontranscriptional and transcriptional events and impacts both the rapid and more prolonged actions of estrogen. Cross-talk from membrane-localized ERs to nuclear ERs can be mediated through growth factor receptor tyrosine kinases, such as epidermal growth factor receptor and IGF-I receptor. Growth factor receptors enact signal transduction to kinases such as ERK and phosphatidylinositol 3-kinase that phosphorylate and activate nuclear ERs, and this can also occur in the absence of sex steroid. A complex relationship between the membrane and nuclear effects of estrogen also involves membrane-initiated phosphorylation of coactivators, recruiting these proteins to the nuclear transcriptosome. Finally, large pools of cytoplasmic ERs exist, and some are localized to mitochondria. The integration of sex steroid effects at distinct cellular locations of its receptor leads to important cellular physiological outcomes and are manifest in both reproductive and nonreproductive organs.
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                Author and article information

                Journal
                Int J Reprod Biomed (Yazd)
                Int J Reprod Biomed (Yazd)
                IJRB
                International Journal of Reproductive Biomedicine
                Yazd : Yazd Research & Clinical Center for Infertility in collaboration with Iranian Society for Reproductive Medicine (Yazd, Iran )
                2476-4108
                2476-3772
                March 2018
                : 16
                : 3
                : 131-148
                Affiliations
                [1 ] Department of Genetics, School of Sciences, Qazvin University of Medical Sciences, Qazvin, Iran.
                [2 ] Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
                [3 ] Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran.
                [4 ] Cellular and Molecular Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
                Author notes
                [* ]Corresponding Author: Hossein Mozdarani, Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Jalal Al Ahmad Expressway, Tehran, Iran. P.O. Box: 14115-116, Email: Mozdarah@modares.ac.ir, Tel: (+98) 9121374831
                Article
                ijrb-16-131
                5944436
                4879c8fe-7da8-4c9b-a02d-95b7bb256f13

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, ( http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 31 December 2016
                : 9 October 2017
                : 13 December 2017
                Categories
                Review Article

                iran,male infertility,genetics,cytogenetic,peripheral blood,sperm

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