Assisted reproductive therapies and imprinting disorders—a preliminary British survey

Sutcliffe, Alastair; Peters, Catherine; Bowdin, Sarah; Temple, I. Karen; Reardon, William; Wilson, Lisa M; Clayton‐Smith, Jill; Brueton, Louise; Bannister, Wendy; Maher, Eamonn R.

doi:10.1093/humrep/dei405

Cited by 241 publications

(205 citation statements)

References 7 publications

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“…It is well know that BWS is more common among patients conceived by artificial reproduction technique; [36][37][38] we encountered a 4.4% prevalence of this phenomenon, confirming data from previous reports and showing a higher prevalence than that reported in the Italian population (1.7%). 39 As concerns tumor risk, the overall prevalence of cancer approximates 8%, consistent with other studies.…”

Section: Phenotypes In Beckwith-wiedemann Syndromesupporting

confidence: 90%

(Epi)genotype–phenotype correlations in Beckwith–Wiedemann syndrome

et al. 2015

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Beckwith-Wiedemann syndrome (BWS) is characterized by cancer predisposition, overgrowth and highly variable association of macroglossia, abdominal wall defects, nephrourological anomalies, nevus flammeus, ear malformations, hypoglycemia, hemihyperplasia, and organomegaly. BWS molecular defects, causing alteration of expression or activity of the genes regulated by two imprinting centres (IC) in the 11p15 chromosomal region, are also heterogeneous. In this paper we define (epi)genotype-phenotype correlations in molecularly confirmed BWS patients. The characteristics of 318 BWS patients with proven molecular defect were compared among the main four molecular subclasses: IC2 loss of methylation (IC2-LoM, n = 190), IC1 gain of methylation (IC1-GoM, n = 31), chromosome 11p15 paternal uniparental disomy (UPD, n = 87), and cyclin-dependent kinase inhibitor 1C gene (CDKN1C) variants (n = 10). A characteristic growth pattern was found in each group; neonatal macrosomia was almost constant in IC1-GoM, postnatal overgrowth in IC2-LoM, and hemihyperplasia more common in UPD (Po0.001). Exomphalos was more common in IC2/CDKN1C patients (Po0.001). Renal defects were typical of UPD/IC1 patients, uretheral malformations of IC1-GoM cases (Po0.001). Ear anomalies and nevus flammeus were associated with IC2/CDKN1C genotype (Po0.001). Macroglossia was less common among UPD patients (Po0.001). Wilms' tumor was associated with IC1-GoM or UPD and never observed in IC2-LoM patients (Po0.001). Hepatoblastoma occurred only in UPD cases. Cancer risk was lower in IC2/CDKN1C, intermediate in UPD, and very high in IC1 cases (P = 0.009).In conclusion, (epi)genotype-phenotype correlations define four different phenotypic BWS profiles with some degree of clinical overlap. These observations impact clinical care allowing to move toward (epi) genotype-based follow-up and cancer screening.

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Section: Phenotypes In Beckwith-wiedemann Syndromesupporting

confidence: 90%

(Epi)genotype–phenotype correlations in Beckwith–Wiedemann syndrome

et al. 2015

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“…46 It is clear that, in the presence of IVF and ICSI, there is an increased risk of the ones caused primarily by epigenetic errors rather than chromosomal problems, such as the case with Beckwith-Weideman syndrome. 47,48 The risk, albeit small, is important because it demonstrates the possibility of other, as yet unidentified, adverse outcomes due to epigenetic errors. Importantly in the context of this review, it does not appear to be an ICSI specific, and therefore, potentially male infertility-related, problem.…”

Section: Overall Defectsmentioning

confidence: 99%

Outcomes for offspring of men having ICSI for male factor infertility

Halliday¹

2011

Asian J Androl

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Since the introduction of intracytoplasmic sperm injection (ICSI) using single sperm isolated from testicular tissue in men with obstructive and non-obstructive azoospermia, or using ejaculated sperm in those with poor semen quality, there have been concerns that this might have adverse effects on the offspring compared to conventional in vitro fertilisation (IVF) and natural conceptions. ICSI is done for reasons other than male factor infertility, and on the whole has not been shown to have any more negative effects than those seen with IVF. There have however, been very few studies of ICSI with a focus on, or large enough numbers to examine, the specific outcomes associated with male factor infertility. From the limited information available in relation to the source of the sperm and aetiology of infertility in the presence of ICSI, there appears to be no increased risk of congenital malformations. There is, however, a small increase in both de novo and inherited chromosome abnormalities. In terms of growth and neurodevelopment, there are very few studies, and so far, no adverse outcomes have been found in young children whose fathers have a sperm defect. The origin of the sperm used in ICSI does not have a major influence on the early life outcomes for the offspring, but transgenerational and epigenetic effects remain unknown. When the male factor infertility is known or thought to be due to a Y-chromosome deletion, this information should be given to the young male offspring at a time that will ensure his own reproductive health and plans are optimized.

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“…Environmental perturbations such as manipulation and culture of embryos in vitro during IVF are expected to influence the epigenetic programming of the developing embryos during this critical period, often leading to nonrandom epigenetic errors such as aberrant DNA methylation and histone modifications (10,11). Indeed, aberrant DNA methylation of some genes has been linked to certain complications, including vascular dysfunction and imprinting disorders, in IVF offspring (12,13).…”

mentioning

confidence: 99%

Impaired imprinted X chromosome inactivation is responsible for the skewed sex ratio following in vitro fertilization

Tan

Kai

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Dynamic epigenetic reprogramming occurs during normal embryonic development at the preimplantation stage. Erroneous epigenetic modifications due to environmental perturbations such as manipulation and culture of embryos during in vitro fertilization (IVF) are linked to various short-or long-term consequences. Among these, the skewed sex ratio, an indicator of reproductive hazards, was reported in bovine and porcine embryos and even human IVF newborns. However, since the first case of sex skewing reported in 1991, the underlying mechanisms remain unclear. We reported herein that sex ratio is skewed in mouse IVF offspring, and this was a result of female-biased peri-implantation developmental defects that were originated from impaired imprinted X chromosome inactivation (iXCI) through reduced ring finger protein 12 (Rnf12)/X-inactive specific transcript (Xist) expression. Compensation of impaired iXCI by overexpression of Rnf12 to up-regulate Xist significantly rescued femalebiased developmental defects and corrected sex ratio in IVF offspring. Moreover, supplementation of an epigenetic modulator retinoic acid in embryo culture medium up-regulated Rnf12/Xist expression, improved iXCI, and successfully redeemed the skewed sex ratio to nearly 50% in mouse IVF offspring. Thus, our data show that iXCI is one of the major epigenetic barriers for the developmental competence of female embryos during preimplantation stage, and targeting erroneous epigenetic modifications may provide a potential approach for preventing IVF-associated complications.in vitro fertilization | sex ratio | X chromosome inactivation | Xist | Rnf12

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Assisted reproductive therapies and imprinting disorders—a preliminary British survey

Abstract: These differences may relate to variations in (i) the molecular mechanisms for disordered imprinting in the different disorders and (ii) the susceptibility of specific imprinting control regions to ART-associated methylation alterations (epimutations).

Cited by 241 publications

References 7 publications

(Epi)genotype–phenotype correlations in Beckwith–Wiedemann syndrome

(Epi)genotype–phenotype correlations in Beckwith–Wiedemann syndrome

Outcomes for offspring of men having ICSI for male factor infertility

Impaired imprinted X chromosome inactivation is responsible for the skewed sex ratio following in vitro fertilization

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