Fetal abnormalities produced after preimplantation exposure of mouse embryos to ammonium chloride

Sinawat, Supat; Hsaio, Wei‐Chih; Flockhart, Jean H.; Kaufman, M. H.; John, Keith; West, John D.

doi:10.1093/humrep/deg429

Cited by 34 publications

(17 citation statements)

References 56 publications

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“…Since the report of ammonium build-up in a culture medium due to L-glutamine [7], several reports have shown that the presence of ammonium ion in a culture medium decreases the cell numbers of the blastocyst and inner cell mass, increases apoptosis, perturbs development after implantation of murine embryos [11,12] and causes fetal abnormalities [10]. These data suggest that EA and BA, in which ammonium build-up has not been detected, do not impair the developmental competence of human embryos compared with BASI and II, in which ammonium build-up has been detected.…”

Section: Discussionmentioning

confidence: 99%

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Medium without Ammonium Accumulation Supports the Developmental Competence of Human Embryos

Hashimoto¹,

Nishihara²,

Murata³

et al. 2008

J. Reprod. Dev.

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Abstract. L-Glutamine has been shown to play an important role during in vitro culture of mammalian embryos. However, it is easily decomposed into ammonium, which is believed to have deleterious effects on preimplantation embryos. In this study, we assessed prospectively the developmental competence of human embryos cultured in medium containing L-glutamine or a novel stable glutamine derivative and vitamins. The subjects of this study were 41 women who underwent IVF/ET treatment from September to November 2006 and from whom 6 or more oocytes were retrieved. Sibling oocytes were randomly divided into EA/BA (EmbryoAssyst ® and BlastAssyst ® containing a novel stable glutamine derivative and vitamins), and BAS groups (BlastAssyst ® system containing L-glutamine). There was no difference in pronuclear formation rate between EA/BA and BAS (74 vs. 69%). The blastulation rates of embryos based on the number of zygotes cultured in EA/BA on Days 5 (Day 0=insemination, 54%) and 6 (63%) were significantly higher (P<0.05) than those cultured in BAS (Day 5: 33% and Day 6: 45%, respectively). The present data indicate that a medium containing a novel stable glutamine derivative and vitamins supports the developmental competence of human embryos.

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Section: Discussionmentioning

confidence: 99%

“…The build-up of ammonium is principally derived from the spontaneous breakdown of glutamine under conditions used for the culture of preimplantation embryos [9]. Several groups of researchers have also suggested that ammonium in media has a deleterious effect on the mouse fetus after embryo transfer [10][11][12].…”

mentioning

confidence: 99%

Medium without Ammonium Accumulation Supports the Developmental Competence of Human Embryos

Hashimoto¹,

Nishihara²,

Murata³

et al. 2008

J. Reprod. Dev.

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“…The supply of high levels of protein or urea periconception increases reproductive tract ammonium levels [17,18], allowing inferences to be drawn from studies investigating ammonium exposure during embryo development that show reduced blastocyst cell numbers and increased apoptosis [19]. The developing fetus and placenta also are influenced by periconception dietary protein supply, including a reduction in pregnancy rates [15], altered fetal development and abnormalities [15,20,21], reduced placental weight and size [7,22], and altered imprinted gene expression in fetal tissue [15,23]. Although evidence to date implicates a lowprotein diet (LPD) in rodents with perturbed embryo, fetal, and offspring development, comparatively less work has focused on the consequences of a high-protein diet (HPD) similar to that consumed in popular weight-loss programs [24].…”

Section: Introductionmentioning

confidence: 99%

Metabolic and Mitochondrial Dysfunction in Early Mouse Embryos Following Maternal Dietary Protein Intervention1

Mitchell

Schulz

Armstrong

et al. 2009

Biology of Reproduction

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Dietary supply of nutrients, both periconception and during pregnancy, influence the growth and development of the fetus and offspring and their health into adult life. Despite the importance of research efforts surrounding the developmental origins of health and disease hypothesis, the biological mechanisms involved remain elusive. Mitochondria are of major importance in the oocyte and early embryo, particularly as a source of ATP generation, and perturbations in their function have been related to reduced embryo quality. The present study examined embryo development following periconception exposure of females to a high-protein diet (HPD) or a low-protein diet (LPD) relative to a medium-protein diet (MPD; control), and we hypothesized that perturbed mitochondrial metabolism in the mouse embryo may be responsible for the impaired embryo and fetal development reported by others. Although the rate of development to the blastocyst stage did not differ between diets, both the HPD and LPD reduced the number of inner cell mass cells in the blastocyst-stage embryo. Furthermore, mitochondrial membrane potential was reduced and mitochondrial calcium levels increased in the 2-cell embryo. Embryos from HPD females had elevated levels of reactive oxygen species and ADP concentrations, indicative of metabolic stress and, potentially, the uncoupling of oxidative phosphorylation, whereas embryos from LPD females had reduced mitochondrial clustering around the nucleus, suggestive of an overall quietening of metabolism. Thus, although periconception dietary supply of different levels of protein is permissive of development, mitochondrial metabolism is altered in the early embryo, and the nature of the perturbation differs between HPD and LPD exposure.

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“…USP14 deficiency in mice has been linked to neuronal dysfunction, and a reduction in levels of the protein following gene knockout in transgenic mice subsequently leads to male sterility (Crimmins et al 2009). Given that one of the gross manifestations of ammonium toxicity after transfer in the mouse is the development of exencephaly (Lane & Gardner 1994, Sinawat et al 2003, the altered gene expression profile reported herein may indicate a possible aetiology of this neural tube defect. In the human blastocyst, increased expression of nicotinamide N-methyltransferase (NNMT), which catalyses the N-methylation of nicotinamide and structurally related pyridines, was also observed.…”

Section: Discussionmentioning

confidence: 88%

“…The activity of this shuttle is essential for the regulation of metabolism during the preimplantation period (Lane & Gardner 2005a), and if its activity is compromised in the blastocyst, then subsequent implantation and fetal development are significantly reduced (Mitchell et al 2009). The alterations in the gene expression of Got1 observed in the presence of ammonium could, therefore, be associated with compromised metabolic activity and regulation and may well be a causative factor for the reduced viability of mouse embryos exposed to ammonium (Lane & Gardner 1994, Sinawat et al 2003. Across the two species studied, both revealed a decrease in the expression of ubiquitin-specific proteases (USPs).…”

Section: Discussionmentioning

confidence: 99%

Human and mouse embryonic development, metabolism and gene expression are altered by an ammonium gradient in vitro

et al. 2013

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Ammonium is generated in culture media by the spontaneous deamination of amino acids at 37 8C and through the metabolism of amino acids by human embryos. The appearance of ammonium is a time-dependent phenomenon and can compromise embryo physiology, development and viability. In this study, the effects of a gradient of ammonium on the development, metabolism and transcriptome of human and mouse embryos were investigated. Pronucleate oocytes were cultured in the presence of an ammonium gradient that mimicked the spontaneous deamination of Eagle's amino acids together with 1 mM glutamine. All embryos were cultured in sequential media G1/G2 at 5% O 2 , 6% CO 2 and 89% N 2 . Human embryo metabolism was assessed through a non-invasive fluorometric analysis of pyruvate consumption. Transcriptome analysis was performed on the resultant blastocysts from both species using a microarray technology. Embryo development prior to compaction was negatively affected by the presence of low levels of ammonium in both species. Human embryo metabolism was significantly inhibited after just 24 and 48 h of culture. Transcriptome analysis of blastocysts from both species revealed significantly altered gene expression profiles, both decreased and increased. Functional annotation of the altered genes revealed the following over represented biological processes: metabolism, cell growth and/or maintenance, transcription, cell communication, transport, development and transcription regulation. These data emphasize the enhanced sensitivity of the cleavage-stage embryo to its environment and highlight the requirement to renew culture media at frequent intervals in order to alleviate the in vitro induced effects of ammonium build-up in the environment surrounding the embryo.

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Fetal abnormalities produced after preimplantation exposure of mouse embryos to ammonium chloride

Cited by 34 publications

References 56 publications

Medium without Ammonium Accumulation Supports the Developmental Competence of Human Embryos

Medium without Ammonium Accumulation Supports the Developmental Competence of Human Embryos

Metabolic and Mitochondrial Dysfunction in Early Mouse Embryos Following Maternal Dietary Protein Intervention1

Human and mouse embryonic development, metabolism and gene expression are altered by an ammonium gradient in vitro

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