[Treatment of sterility in couples: is there an age limit for men?].
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Adult↗
Biomedical subjects
M Auroux
Publications and source records attributed to M Auroux.
Long-term effects of embryo freezing in mice.
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.
Age Factors↗
Effects of cooling and equilibration in DMSO, and cryopreservation of mouse oocytes, on the rates of in vitro fertilization, development, and chromosomal abnormalities.
In a previous study, we have shown that the cryopreservation of mouse oocytes caused increases in the rates of degeneration and of digynic polyploid embryos, while the fertility of frozen-thawed oocytes was decreased. In this study, we have attempted to determine the different stages in the complete freezing-thawing process which are deleterious for the oocytes and the subsequent zygotes. IVF assays showed that DMSO decreased the fertility of oocytes, whereas cooling to 0 degrees C had no effect. DMSO, used at 0 degrees C, was less deleterious for oocytes. Thus, the prefreezing manipulations seem to be important for the quality and fertility of oocytes. However, neither DMSO nor cooling increased the incidence of chromosomal abnormalities in embryos obtained from inseminated exposed oocytes. Therefore, the increased frequency of polyploidy observed in embryos after the cryopreservation of mouse oocytes must correspond to disruption occurring during the freezing-thawing process.
Aneuploidy↗
Chromosome 18 analysis by fluorescence in situ hybridization (FISH) in human blastomeres of abnormal embryos after in vitro fertilization (IVF) attempt.
We performed fluorescence in situ hybridization (FISH) with a chromosome 18-specific probe on human abnormal cleaved embryos, fertilized either by two spermatozoa and exhibiting three pronuclei (3 PN) or normally fertilized and exhibiting two pronuclei (2 PN) with subsequent severe fragmentation and/or blocking. The aim of the study was to evaluate the incidence of chromosome 18 anomalies among these embryos in order to evaluate the FISH efficiency on such material and to obtain more precise and complete data than those obtained with classical cytogenetic analysis. For the 3 PN cleaved embryos, FISH confirmed the frequent regulation towards diploidy (25 per cent) and the high frequency of mosaics (53 per cent). For the 2 PN blocked or damaged embryos, FISH permitted chromosome evaluation, which was otherwise impossible with classical cytogenetic techniques: we also found a high mosaic frequency (45 per cent) with these embryos. If this frequency were the same for normally developing embryos, it would be a major obstacle to the reliability of either chromosomal or genetic preimplantation diagnosis.
Blastomeres↗
[Capabilities and limitations of research].
Assisted human reproduction (AHR) currently solves numerous difficulties caused by sterility in couples. However, it poses some problems whose solutions involve three main directions in research. Fundamental research explores spontaneously occuring phenomena. It shows that over and above common general points of sexual reproduction, mechanisms can differ from one to another. Technical research perfects artificial empirical methods which lead to fertilization, implantation and pregnancy. It shows that success varies from one species to another. Concerning some technologies such as intracytoplasmic sperm injection, successful results began with humans where they seem to be easier to obtain. Research of risks cheks, in animals, the absence of adverse effects of the above techniques for conceptus. It has confirmed the harmfulness of some environmental factors for gametes and zygotes. Moreover, it shows that these negative effects vary between species and within them for strains and sex. For instance, the cryopreservation of mouse embryos leads to changes in the offspring concerning morphophysiological and behavioral features, some of them appearing in elderly subjects. Indeed, these changes vary as a function of strain and sex. These results as a whole show that experimentation on animals can indicate research areas and also give rise to the need for caution. However, if we want to act on human reproduction, they also show, because of the variations in reactivity from one species to another, that the animal model is insufficient and that research in man is essential. From this point of view, a long term follow up of AHR children seems necessary, as well as the need for reflexion concerning the possibility and conditions of research on human embryos.
Animals↗
Cryopreservation of mouse oocytes: mutagenic effects in the embryo?
We have shown in previous studies that the complete cycle of cryopreservation and prefreezing manipulations increases the degeneration and decreases the fecundability of mouse oocytes. The present study confirms these results. Moreover, we show that the increase of polyploidy previously observed in one-cell zygotes derived from frozen-thawed oocytes persists during the early stages of embryonic development. Furthermore, embryos obtained from frozen oocytes or oocytes exposed to prefreezing manipulations show an increase in the frequency of sister chromatid exchanges. Since the estimation of sister chromatid exchange is a sensitive test of mutagenicity, this suggests that the complete cycle of cryopreservation might alter the oocyte and, more particularly, induce DNA damage.
Animals↗
[Age of the father and development].
Testicular ageing affects at the same time the individual and his lineage. In the individual, vascular, endocrine, blood testis barrier and Sertoli cells changes because of age lead a decrease of spermatozoa number and an alteration in their form and motility. These changes lead a gradual decrease of fertility. In the progeny, paternal ageing is responsible for new dominant autosomic mutations which themselves cause different malformations, as achondroplasia, Apert or Recklinghausen disease, Marfan Syndrome etc. and perhaps for certain chromosome X linked recessive mutations as Duchenne myopathy or hemophily A. Moreover, in animal and man, paternal ageing seems responsible for a gradual lowering in the level of progeny cerebral functions. In man, very youthful age is also related to these effects. Thus, the curve corresponding to this phenomenon presents an inverted U-Shape, of which the top corresponds to about thirty years of paternal age. Maternal age does not appear to play a part in this event. On the whole, these results pose the problem of the optimum age for fatherhood.
Adult↗
[The quality of conceptus as a function of father's age].
Testicular ageing affects at the same time the individual and his lineage. In the individual, vascular, endocrine, blood testis barrier and Sertoli cells changes because of age lead a decrease of spermatozoa number and an alteration in their form and motility. These changes lead a gradual decrease of fertility. In the progeny, paternal ageing is responsible for new dominant autosomic mutations which themselves cause different malformations and perhaps for certain chromosome X linked recessive mutations. Moreover, in animal and man, paternal ageing seems responsible for a gradual lowering in the level of progeny cerebral functions. In man, very youthful age was also related to these effects. Maternal age did not appear to play a part in this event. On the whole, these results pose the problem of the optimum age for fatherhood.
Adult↗
The incidence of chromosomal abnormalities in frozen-thawed mouse oocytes after in-vitro fertilization.
Cryopreservation of mouse oocytes induced a high rate of atresia. Frozen oocytes observed immediately after thawing did not exhibit any alteration in the frequency of chromosomal abnormalities, aneuploidy or polyploidy. After in-vitro fertilization attempts, the cleavage rate of frozen-thawed mouse oocytes was decreased. Cytogenetical observations of inseminated eggs also confirmed this decrease in fertilization rate. First and second cleavages were delayed compared to fresh controls but subsequent development to the 4-cell stage was not altered. Freeze-thawing increased the incidence of chromosomal abnormalities in inseminated oocytes but this only concerned the frequency of triploidy and not monosomic or trisomic aneuploidy. The increase in triploidy seemed to be largely due to the presence of digynic embryos. Second polar body retention seemed to be mainly responsible for this high rate of polyploidy.
Aneuploidy↗
Cyclophosphamide in the F0 male rat: physical and behavioral changes in three successive adult generations.
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Abnormalities, Drug-Induced↗
Effect of urogenital infections on sperm parameters and hypofertility in man.
Urogenital infections can notably reduce the sperm's capacity of fecundation by affecting the spermatozoa directly. The aim of this study was to compare the main parameters of the spermogram of 2 groups of hypofertile subjects, the first group presenting negative semen cultures, the second one positive semen cultures. The only significantly different parameter between these 2 groups of hypofertile patients studied was motility. This anomaly alone could explain some states of hypofertility.
Adult↗
[Cytostatic treatment of the male rat: effects on offspring and protection by initial hormonal treatment].
Cytostatic drugs induce the risk of anomalies in progeny. An arrest of spermatogenesis before the onset of such treatment in the male might protect the germ cells against genotoxic effects. In this study we investigate this possibility in rats by giving a hormonal treatment (medroxyprogesterone acetate plus testosterone, MPAT) which reversibly inhibits the spermatogenic process before the cytostatic treatment (cyclophosphamide, CP). Changes in body weight and behavior were found in the progeny of males treated only with CP. These anomalies were partially corrected in the group where the progenitors had received MPAT. These results agree with the hypothesis that quiescent cells are more resistant to cytostatic drugs and justify further research in this area.
Abnormalities, Drug-Induced↗
[Urogenital infection and male fertility].
There is disagreement as to the influence of urogenital infections on male fertility. The causative organisms are not the same according to different authors and ways in which the sperm are examined do not always seem to have the necessary bacteriological precision. A recent study carried out by us has however shown that Ureaplasma urealyticum and E. coli appear to be the bacteria that are most frequently met in cultures from the semen of infertile men. Changes that these bacteria can bring about are: --direct effects, in that the numbers of spermatozoa themselves are diminished as well as their motility, their morphology and their ability to fertilize. From this point of view the connection between the concentration of bacteria in relationship to the concentration of gametes could be important; --indirect effects, in so far as that infection should change the constituent qualities of the seminal fluid and thus have a secondary effect on spermatozoa, as for example the presence of large numbers of polynuclear cells or the formation of antisperm antibodies. Therapeutic trials, which could have helped solve the problem, do not yet seem to have been decisive. But considerable variations in sperm parameters, which by themselves can perhaps affect the antibacterial potency of seminal fluid, could explain why there are variations in success and failure. Finally, emphasis is placed on the need to stick to rigorous bacteriological protocols and to undertake at the same time well codified clinical, biological, epidemiological and experimental studies.
Genital Diseases, Male↗
Within-subject variability of the percentage of morphologically abnormal spermatozoa among fertile men: biological and measurement components.
Two groups of men were studied to determine how much an individual's spermatozoal morphology varies and which part of the variability is due to biological and to measurement variation. A first group of ten subjects each provided five ejaculates; the other group of four subjects each provided one ejaculate, from each of which five smears were prepared, and evaluated twice. The slides were examined in random order and blindly by the same experienced technician. The total within-subject variability of the percentage of abnormal forms was large (SD = 8.8%), as was the component of this variability due to biologic fluctuation (SD = 5.8%). The distribution of the various abnormalities also varied greatly from one ejaculate to another. The results indicate that more work is needed to determine why biological variation exists, and that several ejaculates (three if possible, two at minimum) are needed for an accurate evaluation of spermatozoal morphology, whereas the examination of greater than 100 spermatozoa/ejaculate is not advantageous.
Fertility↗
Cyclophosphamide in the male rat: behavioral effects in the adult offspring.
Cyclophosphamide in a daily dose of 10 mg/kg was injected intraperitoneally in male Wistar rats for 15 days. Two rats each time were killed for testis examination at regular intervals within 100 days following treatment (over 2 spermatogenetic cycles). One hundred days after the end of the treatment, the other rats, whose spermatogenesis had recovered in the meantime, were mated with 3-month-old females. Offspring were evaluated in regard to the mean number per litter, sex ratio, frequency of gross external malformations, growth pattern, mortality in the first 4 months of life and reproductive ability at 6 months of age. Offspring behavior was also examined between 10 and 14 weeks of age. They were evaluated for spontaneous activity and emotionality with an open field test and for learning ability with an avoidance conditioning test. Cyclophosphamide induced a significant decrease in the number of primary spermatocytes and spermatozoa. Only learning ability was altered in the offspring from the treated males, for the animals which succeeded in the avoidance conditioning test did not learn as rapidly as the controls. However, the difference was significant only in the males. Behavioral abnormalities and the possible genetic factors involved are related to the particular concept of 'physioteratogenesis'.
Animals↗
Do non-spermatozoal cells mainly stem from spermiogenesis? Study of 106 fertile and 102 subfertile men.
The various non-spermatozoal cell types in the semen of 106 fertile (F) and 102 subfertile (SF) men were described and their relative proportions estimated. About 94% (F) and 90% (SF) were found to be germinal elements, among which, respectively, about 27% and 51% were spermatids, 48% and 36% residual bodies, 19.4% and 2.6% primary spermatocytes, 0.03% and 0.61% spermatogonia. The epithelial cells and blood cells represented about 6% (F) and 10% (SF) of the non-spermatozoal cells; in F men 5.3% and in SF men 9.5% were found to be polymorphonuclear leucocytes. In SF men the predominance of spermatids might be due to a particular fragility of spermiogenesis. To the three stages of spermatogenesis-the gonial multiplication, meiosis, and spermiogenesis-might correspond three specific pathologies. A pathology of the very germ cell production was thus suggested, as well as a pathology of the means by which the final product would be controlled. The Sertoli cell was supposed to be mainly involved in the latter process.
Cell Count↗
Testicular aging: vascularization and gametogenesis modifications in the Wistar rat.
A light microscopic study was carried out on testicular aging in the Wistar rat at the ages of 7, 12, 24, 40, 56, 72, 104, and 124 weeks. The following tissular modifications were observed: a progressive decrease in capillary density, a gradually reduced spermatogenic production, and a progressive increase of degenerating tubular areas. The following two questions were raised: (1) Are the vascular modifications responsible for the other alterations? (2) Do the anomalies inducing a decreased number of spermatozoa simultaneously lead to genetic alterations in the morphologically normal spermatozoa with fertilizing ability? This question is particularly interesting owing to our current knowledge of the consequences of the father's age on offspring.
Aging↗