Aneuploidy In Oocytes Research Articles

Aneuploidy in mouse oocytes and 1-cell zygotes after oral dosages of griseofulvin

Aneuploidy in mouse oocytes and 1-cell zygotes after oral dosages of griseofulvin

Are clinical and biological IVF parameters correlated with chromosomal disorders in early life: a multicentric study.

A multicentric study was carried out to analyse in a large series: (i) the chromosomal status of unfertilized oocytes, (ii) errors at fertilization and (iii) the chromosomal complement of cleaved embryos. Parameters such as type of sterility, maternal age, stimulation treatment, doses of gonadotrophins administered and oocyte preincubation time before insemination were studied in relation to the incidence of chromosome abnormalities. Twenty-six per cent of the unfertilized oocytes and 29.2% of the embryos had chromosome anomalies. Maternal age significantly increased the rate of aneuploidy in oocytes: 38% in patients over 35 years (versus 24% in younger patients). Fertilization-related abnormalities were significant, i.e. 1.6% parthenogenesis and 6.4% polyploidy. Unexplained infertility was correlated with an increase in the rate of parthenogenesis (4.2%) when compared with tubal infertility (1.2%). Triploidy was found to be correlated with three parameters. A lower rate of triploidy was observed in the group of couples referred because of male sterility (1.9% versus 6.3% for tubal sterility), in HMG-treated patients (2.4% versus 7% with analogues of LHRH/HMG) and with a short 2-h preincubation time before insemination (3% versus 7.2% for greater than 2 h). A general model for natural selection against embryos carrying a chromosome imbalance was proposed.

The CBA mouse as a model for age-related aneuploidy in man: studies of oocyte maturation, spindle formation and chromosome alignment during meiosis

To elucidate the possible mechanism of disturbances in chromosome segregation leading to the increase in aneuploidy in oocytes of aged females we examined the meiotic spindles of CBA/Ca mice. Employing immunofluorescence with an anti-tubulin antibody, and human scleroderma serum, as well as 4'-6-diamidino-2-phenylindole (DAPI) staining of chromosomes the microtubular cytoskeleton could be visualized, and the behaviour of chromosomes and centromeres of oocytes spontaneously maturing in vitro could be studied. The morphology of spindles during the first meiotic division was not conspicuously different in oocytes from young and aged mice as far as the cytoskeletal elements were concerned. Neither multipolar spindles nor pronounced cytoplasmic asters appeared in oocytes of mice approaching the end of their reproductive life (9 months and older). Oocytes of aged females also did not exhibit any sign of premature separation of parental chromosomes at prophase, obvious malorientations of bivalents, or significant lagging of chromosomes during ana- and telophase. Metaphase I with all bivalents aligned at the spindle equator appeared to be a relatively brief stage in oocyte development compared with pro- and prometaphase. Therefore, already slight disturbances occurring in the timing of the developmental programme which leads to a premature anaphase transition may be responsible for the high incidence of chromosomally unbalanced gametes in aged females, rather than non-separation and lagging of chromosomes during late ana- and telophase. In a second set of experiments we compared the metaphase II spindles of spontaneously ovulated oocytes obtained from animals at different ages. Previous studies have shown that spindle length and chromosome alignment may be altered in cells predisposed to aneuploidy.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromosome studies in oocytes and zygotes from an IVF programme.

Chromosome studies have been carried out in 117 oocytes, 17 one-cell zygotes and four, two- to four-cell zygotes in our IVF programme. Three apparently unfertilized oocytes were, in fact, diploid zygotes. Two of 14 apparently polyspermic zygotes were also diploid. One zygote with four pronuclei was pentaploid. This indicates that pronuclei can either be confused with other cytoplasmic structures, like vacuoles, or be eliminated. Endoreduplication was observed in one tetraploid, apparently polyspermic zygote, and in one two-cell degenerated zygote. The incidence of aneuploidy in unfertilized oocytes, taken as twice the level of hyperhaploidy, was 15.4%. Five oocytes showed fragmented metaphase II chromosomes (4.3%). The incidence of unreduced oocytes, due to a lack of extrusion of the first polar body, was 6.8%. Thus the total number of potentially aneuploid, polyploid or non-viable zygotes due to chromosome aberrations in the oocyte was 26.5%.

Aging and aneuploidy in human oocytes and follicular cells.

The incidence of chromosomal aneuploidy in the oocyte and surrounding follicular cells in women of different ages was investigated. Oocytes and granulosa cells derived from ovarian specimens from a random population of 289 adult patients ages 16 to 76 years undergoing gynecologic surgery for nonovarian pathology were cultured for short periods, and cytogenetic preparations were scored for chromosome number and morphology. Of 91 oocytes harvested at second meiotic metaphase, five oocytes revealed a chromosomal abnormality. Cytogenetic analysis of the granulosa cells revealed aneuploid cells as well as complements with structural changes. A significant difference between the percentage of granulosa cell aneuploidy in the 25 to 34 years group and all other age groups was found, suggesting a decrease of the tendency for granulosa cells to exhibit aneuploidy in older age groups. Previous reports of aneuploidy in human ovary and other somatic cell types suggest that follicular cells behave differently in their response to aging. There also would appear to be a difference between the chromosomal response of oocytes and granulosa cells to aging.

Aneuploidy induced by bleomycin in oocytes of Drosophila melanogaster: studies with the aneuploidy pattern method.

The induction of aneuploidy (numerical chromosome aberrations) in oocytes of Drosophila melanogaster by the antitumor drug bleomycin (BLM) was studied with the "aneuploidy pattern method." The aneuploidy pattern obtained after feeding BLM at a concentration of 50 micrograms/ml to Drosophila females resembles the pattern obtained after X-irradiation (3,000 R). This emphasizes the radiomimetic nature of BLM. In addition, new control material is presented. The new control pattern agrees well with that obtained earlier.

The solvent dimethylsulfoxide (DMSO) does not induce aneuploidy in oocytes of Drosophila melanogaster.

Both with a conventional method and with the "aneuploidy pattern method" we tested whether the solvent dimethylsulfoxide (DMSO) is able to induce aneuploidy (numerical chromosome aberrations) in oocytes of Drosophila melanogaster. DMSO was fed as a 2% solution to Drosophila females. No evidence for a mutagenic activity was obtained. This finding and the negative results reported by other authors for other types of mutation in Drosophila show that DMSO can be used as a solvent for chemical agents in mutagenicity screening in Drosophila melanogaster.

Detection of nondisjunction in mammals.

Methods have been developed in the past to assess spontaneous and induced chromosomal aneuploidy in germ cells and in early pre- and postimplantation mammalian embryos. Some of these methods yield still more information when combined with chromosome banding techniques. Various chemicals and x-rays have been tested in mammalian oogenesis and x-rays in spermatogenesis. The inference may be drawn from these studies that spontaneous nondisjunction is considered to occur only rarely in mouse and hamster oogenesis and spermatogenesis. X-rays induce nondisjunction during male and femlae meiosis, thus giving rise to significantly more aneuploid oocytes and F1 embryos. The alkylating agents trenimone and cyclophosphamide induce chromosomal missegregation in oocytes; the incidence depends on the dose injected. Hormones used as oral contraceptives did cause aneuploidy in oocytes, but only after daily treatment with high doses. Hormones used for stimulated ovulation did not interfere with chromosome segregation in the mouse and Chinese and Syrian hamsters. The following problems may be considered in futre studies: the problem of a species-specificity for induced nondisjunction; the question of a stage sensitivity (transplacental treatment); what happens after chronic exposure, also at low doses; the presence of a threshold; the existence of a dose-effect relation; the nature of cellular target(s) responsible for induced nondisjunction (spindle, regulatory proteins for polymerization of microtubules and ther depolymerization, centrioles, centromeres, RNA, or gene expression); whether DNA is involved and whether repair capacity plays a role.

Detection of Nondisjunction in Mammals

Methods have been developed in the past to assess spontaneous and induced chromosomal aneuploidy in germ cells and in early pre- and postimplantation mammalian embryos. Some of these methods yield still more information when combined with chromosome banding techniques. Various chemicals and x-rays have been tested in mammalian oogenesis and x-rays in spermatogenesis. The inference may be drawn from these studies that spontaneous nondisjunction is considered to occur only rarely in mouse and hamster oogenesis and spermatogenesis. X-rays induce nondisjunction during male and femlae meiosis, thus giving rise to significantly more aneuploid oocytes and F1 embryos. The alkylating agents trenimone and cyclophosphamide induce chromosomal missegregation in oocytes; the incidence depends on the dose injected. Hormones used as oral contraceptives did cause aneuploidy in oocytes, but only after daily treatment with high doses. Hormones used for stimulated ovulation did not interfere with chromosome segregation in the mouse and Chinese and Syrian hamsters. The following problems may be considered in futre studies: the problem of a species-specificity for induced nondisjunction; the question of a stage sensitivity (transplacental treatment); what happens after chronic exposure, also at low doses; the presence of a threshold; the existence of a dose-effect relation; the nature of cellular target(s) responsible for induced nondisjunction (spindle, regulatory proteins for polymerization of microtubules and ther depolymerization, centrioles, centromeres, RNA, or gene expression); whether DNA is involved and whether repair capacity plays a role.

Experimental production of aneuploidy in mouse oocytes.

The normal course of meiosis can be interrupted in cultured mouse oocytes by exposre to low temperature (23 degrees C). Re-transfer of the oocytes to a 37 degrees C environment will permit the meiotic process to resume and progress as usual to second metaphase. However, a significant number of oocytes treated in this manner prove to contain abnormal numbers of chromosomes.