Cryopreservation of Mouse Oocytes: Mutagenic Effects in the Embryo?1

Bouquet, M.; Selva, J.; Auroux, M

doi:10.1095/biolreprod49.4.764

Cited by 42 publications

(11 citation statements)

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“…A much larger number of studies have looked for indirect evidence of genetic damage, such as chromosomal anomalies. Enough of these studies have found evidence of such damage to be a cause for concern (Rudd et al, 1989 ;Schmidt-Preuss et al, 1990 ;Casati et al, 1992 ;Bouquet et al, 1993). The advent of cryopreservation in D. melanogaster offers a good opportunity to perform large-scale genetic analyses of the effects of such techniques in a complex metazoan.…”

Section: Introductionmentioning

confidence: 99%

The effect of cryopreservation on the lethal mutation rate in Drosophila melanogaster

et al. 1997

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Although cryopreservation is routinely used for the storage of a range of biological organisms, few studies have been conducted to determine whether cryopreservation increases the frequency of mutation. A procedure for the cryopreservation of Drosophila melanogaster embryos has recently been developed. Cryopreservation of D. melanogaster is of special interest to geneticists and evolutionary biologists because it would make it possible to assay control and experimental populations simultaneously during long-term studies. Before cryopreserved embryos can be used for such studies, it is first necessary to show that cryopreservation is not mutagenic. We tested for mutagenic effects or cryopreservation in D. melanogaster embryos with an X-linked, recessive lethal assay. The mutation rates of cryopreserved and control flies were not significantly different. We can be 95% certain that cryopreservation does not increase mutation by a factor greater than 2.39. This is the first quantitative estimate of the mutagenic effect of cryopreservation on the germ line of a metazoan. The results are reassuring when considering the genetic impact of cryopreservation on mammalian gametes and embryos.

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Section: Introductionmentioning

confidence: 99%

The effect of cryopreservation on the lethal mutation rate in Drosophila melanogaster

et al. 1997

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“…The current opinion-that embryo freezing has no late consequencesrelies on the negative results of previous experimental studies (10)(11)(12)(13)(14)(15) and on common experience in cattle and humans. More recently, however, damage to the genetic material from freezing has been reported (16)(17)(18). Furthermore, in domestic species as in humans, investigations have mainly focused on patent defects at birth or in early life.…”

mentioning

confidence: 99%

Long-term effects of embryo freezing in mice.

Dulioust

Toyama

Busnel

et al. 1995

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

107

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Embryo cryopreservation does not induce clear-cut anomalies at detectable rates, but several mechanisms exist for nonlethal damage during the freeze-thaw process, and the risk of moderate or delayed consequences has not been extensively investigated. In a long-term study including senescence, we compared cryopreserved and control mice for several quantitative traits. Significant differences were seen in morphophysiological and behavioral features, some of them appearing in elderly subjects. Thus, apart from its immediate toxicity, embryo cryopreservation, without being severely detrimental, may have delayed effects. These results, consistent with other findings, question the neutrality of artificial reproductive technologies and draw attention to the preimplantation stages in developmental toxicology.Embryo freezing is common practice in several species including humans. This technique can be lethal to some embryos but is not considered to have any delayed effect. However, several arguments question such a viewpoint. Several targets of major importance to further development and life are present in the early mammalian embryo: the nuclear DNA, of course, and also the mitochondrial genome (1) and early processes such as those related to imprinting (2, 3), which are completed after fertilization. Freezing-thawing involves dramatic cellular and biochemical changes, such as enzyme inactivation (4-6), ionic disturbances, or attack by free radicals (7-9), that through various pathways could damage these critical components or processes. The current opinion-that embryo freezing has no late consequencesrelies on the negative results of previous experimental studies (10-15) and on common experience in cattle and humans. More recently, however, damage to the genetic material from freezing has been reported (16-18). Furthermore, in domestic species as in humans, investigations have mainly focused on patent defects at birth or in early life. However, for complex organisms in which many genetic changes, especially mitochondrial, may have only mild or delayed effects, such indicators provide only a limited assessment of the broad spectrum of anomalies that could result from mutagenic or toxic action on the early embryo.More detailed investigation and long-term follow-up are necessary to comprehensively assess embryo-freezing consequences in mammals. We report here the results of a study comparing mice derived from cryopreserved and control embryos in several morphophysiological, sensorimotor, and behavioral traits, from birth to senescence. The experiment was done on two different hybrid genotypes: C57BL6/CBA F1 (B6CBA) and C3H/DBA2 F1(C3D2). MATERIALS AND METHODSEmbryo Collection. After superovulation (pregnant mare serum gonadotropin, 5 international units, and human chorionic gonadotropin, 5 international units, 48 hr later), 8-weekold C57BL/6JIco (B6) and C3H/OuJIco (C3) females were mated with CBA/JIco (CBA) and DBA/2JIco (D2) males, respectively. B6CBA and C3D2 embryos were collected in M2 medium (19), at the two...

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“…Some of these effects vary as a function of strain and sex. Regarding these results, it is interesting, on the one hand, that other teams [62] as well as ourselves [63,64] have ob served, in situations with known genetic risks, similar abnormalities in systems where the genetic determination is very polygenicsuch as the CNS -and on the other hand, that, as we have shown, oocyte cryopreservation seems to lead to mutations in derived em bryos [81], Therefore, the cryopreservation of em bryos does not appear to be neutral in terms of effect. Moreover, the variations in effects from one genotype to another correspond to what is known about the forms of action of teratogenic factors [82].…”

Section: The Particular Case Of a Ssiste D Procreationsmentioning

confidence: 59%

Behavioral Teratogenesis: An Extension to the Teratogenesis of Functions

Auroux

1997

Neonatology

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Major malformations correspond to pathology during the first 2 months of gestation. Thereafter, histological and biochemical abnormalities can result from different negative maternal incidents and, without obvious malformations, change the phenotype of the conceptus. These abnormalities lead to essentially functional disorders often compatible with life and to more or less serious handicaps. All systems, when they arrive at such a stage of development, can be theoretically involved. The central nervous system (CNS) offers a very clear example of such weaknesses because its maturation is particularly long and susceptible to changes even after birth. The steps of this maturation overlap and form a continuum reflected in the pathology. Mental retardation occurring in children born of mothers who were subjected to atomic radiation, or ingested methylmercury from industrial waste, or who suffered the effects of lead, alcohol or tobacco constitutes a clear clinical example. Animal experiments confirm these data, adding pathogenic explanations. These experiments also explore the possible consequences that some medical techniques such as modern reproductive technology, for example embryo freezing, can have on the development of the conceptus. Toxic substances or drugs can also be responsible for such abnormalities through a genetic attack on spermatogenesis. Behavioral teratogenesis also opens a larger persepective related to the optimal quality of the conceptus and the determining factors, from stress or dietary factors during apparently normal pregnancy to paternal age at the moment of conception. Finally, given that other systems than the CNS can be involved in histological or biochemical abnormalities, such as the reproductive system, we must ask what other types of functional pathology can be induced by interventions on gametes, the embryo and the fetus. Thus, behavioral teratogenesis leads to the teratogenesis of functions.

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Cryopreservation of Mouse Oocytes: Mutagenic Effects in the Embryo?1

Cited by 42 publications

References 0 publications

The effect of cryopreservation on the lethal mutation rate in Drosophila melanogaster

The effect of cryopreservation on the lethal mutation rate in Drosophila melanogaster

Long-term effects of embryo freezing in mice.

Behavioral Teratogenesis: An Extension to the Teratogenesis of Functions

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