Genetic testing and counselling for male infertility

Krausz, Csilla; Chianese, Chiara

doi:10.1097/med.0000000000000058

Cited by 39 publications

(21 citation statements)

References 33 publications

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“…Infertility is a complex problem and associated with several factors such as hormonal, biological, genetic and lifestyle factors (Krausz & Chianese, 2014;Yassin, Lubbad, Taha, Laqqan, & Jamiea, 2017). About 15% of couples worldwide suffer from infertility problem (Inhorn & Patrizio, 2015), in addition, male infertility problems considered as a major cause of infertility in human couples (Anawalt, 2013).…”

Section: Introductionmentioning

confidence: 99%

Alterations in DNA methylation patterns and gene expression in spermatozoa of subfertile males

Laqqan

Hammadeh

2017

Andrologia

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This study was designed to evaluate the DNA methylation patterns and gene expression in spermatozoa from subfertile males. Thirty samples were subjected to 450K arrays as a screening study to evaluate the variation in sperm DNA methylation levels between cases and controls groups, and then three CpG sites (cg07227024, cg05813498 and cg23081194) have the highest difference in methylation levels and located within ALS2CR12, GAA and UBE2G2 genes respectively; these were selected for further analysis using deep bisulphite sequencing and qPCR in 136 samples (64 proven fertile males "controls" and 72 subfertile males "cases"). A significant difference in the methylation level was found between cases and controls at two CpGs, six CpGs and three CpGs in ALS2CR12, GAA and UBE2G2 gene-related amplicon respectively. Besides, the qPCR results showed a significant change in the expression levels of GAA, UBE2G2 and ALS2CR12 gene in cases compared to the controls (p ≤ .00001). In conclusion, the methylation levels at CpGs in GAA, UBE2G2 and ALS2CR12 gene amplicons were significantly different in subfertile compared to proven fertile males. In addition, a significantly different was showed in the expression levels of GAA, UBE2G2 and ALS2CR12 genes in subfertile males compared to proven fertile males.

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Section: Introductionmentioning

confidence: 99%

Alterations in DNA methylation patterns and gene expression in spermatozoa of subfertile males

Laqqan

Hammadeh

2017

Andrologia

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“…This is particularly interesting because only microdeletions on the Y chromosome causative of spermatogenic failure are well described. Still, in about 40% of male factor infertility the etiology remains unknown (Krausz & Chianese, ).…”

Section: Discussionmentioning

confidence: 99%

Ocular albinism with infertility and late‐onset sensorineural hearing loss

Fabian‐Jessing

Vestergaard

Plomp

et al. 2018

American J of Med Genetics Pt A

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Ocular albinism type 1 (OA1) is caused by mutations in the GPR143 gene located at Xp22.2. The manifestations, which are due to hypopigmentation, are confined to the eyes and optic pathway. OA1 associated with late-onset sensorineural hearing loss was previously reported in a single family and hypothesized to be caused by a contiguous gene deletion syndrome involving GPR143 and the adjacent gene, TBL1X. Here, we report on a family with OA1, infertility, late-onset sensorineural hearing loss, and a small interstitial Xp microdeletion including the GPR143, TBL1X, and SHROOM2 genes. In addition, we re-examined a patient previously described with OA1, infertility and a similar Xp deletion with audiologic follow-up showing a late-onset sensorineural hearing loss. Our results raise an intriguing question about the possibility for TBL1X (absence) involvement in this type of hearing loss. However, our study cannot claim a causative relationship and more convincing evidence is needed before the hypothesis can be accepted that TBL1X could be involved in late-onset sensorineural hearing loss and that ocular albinism with late-onset sensorineural hearing loss can present itself as a contiguous gene deletion/microdeletion syndrome. The finding of infertility in all affected male patients demonstrates that this deletion, including the SHROOM2 gene, may be a potentially causative X-linked genetic factor of male infertility.

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“…Unfortunately, the genetic etiology remains elusive in many cases. More research on the identification of genomic mutations that cause subfertility is necessary in this respect (Visser and Repping, 2010; Tuttelmann et al , 2011; Krausz and Chianese, 2014). A recent article describes that CRISPR-Cas9 was exploited to successfully eradicate porcine endogenous retroviruses with the copy number as high as 62 in a porcine cell line (Yang et al , 2015), showing the robustness and versatility of CRISPR.…”

Section: Clinical and Technical Hurdles And Drawbacksmentioning

confidence: 99%

“…While the etiology of a severe male factor remains largely unknown, a few genetic defects (Visser and Repping, 2010; Tuttelmann et al , 2011; Krausz and Chianese, 2014), including structural and numerical chromosomal abnormalities (de Kretser, 1997; Oates, 2008) and Y-chromosome deletions (Kuroda-Kawaguchi et al , 2001; Noordam and Repping, 2006), have been identified to associate with a severe male factor-induced subfertility. In addition, male subfertility can be attributed to previous gonadotoxic treatment (Meistrich, 2013).…”

Section: Introductionmentioning

confidence: 99%

Spermatogonial stem cell autotransplantation and germline genomic editing: a future cure for spermatogenic failure and prevention of transmission of genomic diseases

Mulder

Zheng

Jan

et al. 2016

Hum. Reprod. Update

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BACKGROUNDSubfertility affects approximately 15% of all couples, and a severe male factor is identified in 17% of these couples. While the etiology of a severe male factor remains largely unknown, prior gonadotoxic treatment and genomic aberrations have been associated with this type of subfertility. Couples with a severe male factor can resort to ICSI, with either ejaculated spermatozoa (in case of oligozoospermia) or surgically retrieved testicular spermatozoa (in case of azoospermia) to generate their own biological children. Currently there is no direct treatment for azoospermia or oligozoospermia. Spermatogonial stem cell (SSC) autotransplantation (SSCT) is a promising novel clinical application currently under development to restore fertility in sterile childhood cancer survivors. Meanwhile, recent advances in genomic editing, especially the clustered regulatory interspaced short palindromic repeats-associated protein 9 (CRISPR-Cas9) system, are likely to enable genomic rectification of human SSCs in the near future.OBJECTIVE AND RATIONALEThe objective of this review is to provide insights into the prospects of the potential clinical application of SSCT with or without genomic editing to cure spermatogenic failure and to prevent transmission of genetic diseases.SEARCH METHODSWe performed a narrative review using the literature available on PubMed not restricted to any publishing year on topics of subfertility, fertility treatments, (molecular regulation of) spermatogenesis and SSCT, inherited (genetic) disorders, prenatal screening methods, genomic editing and germline editing. For germline editing, we focussed on the novel CRISPR-Cas9 system. We included papers written in English only.OUTCOMESCurrent techniques allow propagation of human SSCs in vitro, which is indispensable to successful transplantation. This technique is currently being developed in a preclinical setting for childhood cancer survivors who have stored a testis biopsy prior to cancer treatment. Similarly, SSCT could be used to restore fertility in sterile adult cancer survivors. In vitro propagation of SSCs might also be employed to enhance spermatogenesis in oligozoospermic men and in azoospermic men who still have functional SSCs albeit in insufficient numbers. The combination of SSCT with genomic editing techniques could potentially rectify defects in spermatogenesis caused by genomic mutations or, more broadly, prevent transmission of genomic diseases to the offspring. In spite of the promising prospects, SSCT and germline genomic editing are not yet clinically applicable and both techniques require optimization at various levels.WIDER IMPLICATIONSSSCT with or without genomic editing could potentially be used to restore fertility in cancer survivors to treat couples with a severe male factor and to prevent the paternal transmission of diseases. This will potentially allow these couples to have their own biological children. Technical development is progressing rapidly, and ethical reflection and societal debate on the use of SSCT with ...

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Genetic testing and counselling for male infertility

Cited by 39 publications

References 33 publications

Alterations in DNA methylation patterns and gene expression in spermatozoa of subfertile males

Alterations in DNA methylation patterns and gene expression in spermatozoa of subfertile males

Ocular albinism with infertility and late‐onset sensorineural hearing loss

Spermatogonial stem cell autotransplantation and germline genomic editing: a future cure for spermatogenic failure and prevention of transmission of genomic diseases

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