Esterilidad Masculina 2015
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ORAL PRESENTATION Open Access Genetics of male infertility: status and prospects Eberhard Nieschlag 1,3* , Frank Tüttelmann 2 , Mohammed A. Beg 3 From 2nd International Genomic Medical Conference (IGMC 2013) Jeddah, Kingdom of Saudi Arabia. 24-27 November 2013 The incidence of infertility is about 15% in couples of childbearing age. In half of these couples a fertility pro- blem exists on the male side. However, causes of male infertility are still to a large extent unknown. Today, in about 20% of patients with azoospermia or severe oligo- zoospermia genetic causes have been identified and further progress is expected from genetic investigations. The Klinefelter syndrome represents the most frequent form of human aneuploidies and male infertility. The high incidence of 1:500 in the general male population increases to 1:50 in infertility centres. Ninety percent of the affected men show azoospermia. In recent years it became possible to obtain viable sperm by testicular biopsy, followed by TESE/ICSI, resulting in pregnancies. Since these sperm may derive from isolated spermatogonia with a regular karyotype, most of the children have normal karyotypes. AZF a, b, and c deletions of the Y chromosome are found in men with severe infertility. The incidence among patients with very low sperm counts or azoosper- mia varies between 2.5 and 10 %. From patients with AZFc deletions sperm may be retrieved from testicular biopsies and induction of pregnancy with these sperm is possible by applying TESE/ICSI. Patients with AZF a and b deletions mostly have complete Sertoli-cell-only-syn- drome (SCOS) and have no chances for paternity. Male children of men with microdeletions in the AZF region have the same deletions as their fathers and are likely to be infertile themselves. Mutations of the CFTR gene affect functioning of the chloride ion channels in the epithelial cell membranes leading to cystic fibrosis and congenital bilateral absence of the vas deferens (CBAVD). CBAVD may occur as a minimal form of cystic fibrosis (CF). Before TESE/ICSI is applied, the status of the female partner needs to be determined in order to avoid offspring suffering from CF. A number of genes mutated in isolated hypogonadotro- pic hypogonadism (IHH) and Kallmann syndrome have been identified Oligozoospermic men with combined sin- gle nucleotide polymorphism of FSHR 2039A>G and FSHB-211G>T may benefit from FSH therapy. Although men may remain fertile lifelong, a slow decline of reproductive capacities occurs beyond the age of 45 and specific gene mutations e.g. of the FGFR2 and FGRF3 genes causing Apert syndrome and achondroplasia may increase, affecting offspring. Investigations into epigenetics such as methylation abnormalities, transcriptome analysis as well as single and combined single-nucleotide polymorphism genotypes and whole genome analysis in individual sperm may lead to the identification of further genetic associations with infertility. Authors’ details 1 Center of Reproductive Medicine and Andrology, University of Münster, 48129 Münster, Germany. 2 Institute of Human Genetics, University of Münster, 48129 Münster Germany. 3 Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia. Published: 2 April 2014 doi:10.1186/1471-2164-15-S2-O25 Cite this article as: Nieschlag et al.: Genetics of male infertility: status and prospects. BMC Genomics 2014 15(Suppl 2):O25. * Correspondence: [email protected] 1 Center of Reproductive Medicine and Andrology, University of Münster, 48129 Münster, Germany Full list of author information is available at the end of the article Nieschlag et al. BMC Genomics 2014, 15(Suppl 2):O25 http://www.biomedcentral.com/1471-2164/15/S2/O25 © 2014 Nieschlag et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Esterilidad Masculina
Transcript of Esterilidad Masculina 2015
ORAL PRESENTATION Open Access
Genetics of male infertility: status and prospectsEberhard Nieschlag1,3*, Frank Tüttelmann2, Mohammed A. Beg3
From 2nd International Genomic Medical Conference (IGMC 2013)Jeddah, Kingdom of Saudi Arabia. 24-27 November 2013
The incidence of infertility is about 15% in couples ofchildbearing age. In half of these couples a fertility pro-blem exists on the male side. However, causes of maleinfertility are still to a large extent unknown. Today, inabout 20% of patients with azoospermia or severe oligo-zoospermia genetic causes have been identified andfurther progress is expected from genetic investigations.The Klinefelter syndrome represents the most frequent
form of human aneuploidies and male infertility. The highincidence of 1:500 in the general male populationincreases to 1:50 in infertility centres. Ninety percent ofthe affected men show azoospermia. In recent years itbecame possible to obtain viable sperm by testicularbiopsy, followed by TESE/ICSI, resulting in pregnancies.Since these sperm may derive from isolated spermatogoniawith a regular karyotype, most of the children have normalkaryotypes.AZF a, b, and c deletions of the Y chromosome are
found in men with severe infertility. The incidenceamong patients with very low sperm counts or azoosper-mia varies between 2.5 and 10 %. From patients withAZFc deletions sperm may be retrieved from testicularbiopsies and induction of pregnancy with these sperm ispossible by applying TESE/ICSI. Patients with AZF a andb deletions mostly have complete Sertoli-cell-only-syn-drome (SCOS) and have no chances for paternity. Malechildren of men with microdeletions in the AZF regionhave the same deletions as their fathers and are likely tobe infertile themselves.Mutations of the CFTR gene affect functioning of the
chloride ion channels in the epithelial cell membranesleading to cystic fibrosis and congenital bilateral absenceof the vas deferens (CBAVD). CBAVD may occur as aminimal form of cystic fibrosis (CF). Before TESE/ICSI is
applied, the status of the female partner needs to bedetermined in order to avoid offspring suffering from CF.A number of genes mutated in isolated hypogonadotro-
pic hypogonadism (IHH) and Kallmann syndrome havebeen identified Oligozoospermic men with combined sin-gle nucleotide polymorphism of FSHR 2039A>G andFSHB-211G>T may benefit from FSH therapy.Although men may remain fertile lifelong, a slow decline
of reproductive capacities occurs beyond the age of 45 andspecific gene mutations e.g. of the FGFR2 and FGRF3genes causing Apert syndrome and achondroplasia mayincrease, affecting offspring.Investigations into epigenetics such as methylation
abnormalities, transcriptome analysis as well as single andcombined single-nucleotide polymorphism genotypes andwhole genome analysis in individual sperm may lead tothe identification of further genetic associations withinfertility.
Authors’ details1Center of Reproductive Medicine and Andrology, University of Münster,48129 Münster, Germany. 2Institute of Human Genetics, University ofMünster, 48129 Münster Germany. 3Center of Excellence in GenomicMedicine Research, King Abdulaziz University, Jeddah, Kingdom of SaudiArabia.
Published: 2 April 2014
doi:10.1186/1471-2164-15-S2-O25Cite this article as: Nieschlag et al.: Genetics of male infertility: statusand prospects. BMC Genomics 2014 15(Suppl 2):O25.
* Correspondence: [email protected] of Reproductive Medicine and Andrology, University of Münster,48129 Münster, GermanyFull list of author information is available at the end of the article
Nieschlag et al. BMC Genomics 2014, 15(Suppl 2):O25http://www.biomedcentral.com/1471-2164/15/S2/O25
© 2014 Nieschlag et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the CreativeCommons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, andreproduction in any medium, provided the original work is properly cited.
