More and more “in vitro” children appear every year – in developed countries such children share about 1-3% of all newborns. Are assisted reproductive technologies (ART) safe? After summarizing world scientific data Russian medical genetics have tried their best in studying risks of genomic imprinting diseases.

What is genomic imprinting? Normal development of mammals requires functional differences in gene sets of mother and father. Some certain genes activate only mother’s copy, others use only father’s information. Mechanism, regulating functional differences of parent genomes, is called genomic imprinting. This process is complex and has many stages, starting in parental gametes, where special enzymes mark and deactivate necessary genes, and continuing after fertilization. Failure during marking causes serious pathologies, and human beings are known to suffer from several diseases of genomic imprinting.

Genomic imprinting depends on external factors, and researchers expect ART to have some effect on this process. Proof of this effect was detected in experiments with artificial fertilization of animals. Cultured embryos of sheep and cattle sometimes show “large offspring syndrome” – baby animals sometimes exceed normal weight more than two times. Another important fact is that fetuses often die during pregnancy and delivery, moreover, pregnancy lasts too long and confinement is difficult. Studies show that dead fetuses and little animals have internal pathologies. Animal “large offspring syndrome”, caused by failures in genomic imprinting, looks similar to human Beckwith-Wiedemann syndrome, caused by same reasons. This disease usually results in large newborn children with multiple pathologies. The syndrome happens once in 12-15 thousand deliveries, however, children, conceived by means of assisted reproductive technologies, suffer from this disease much more often.

Scientists suggest several hypotheses, explaining why genomic imprinting diseases happen much oftener in case, when assisted reproductive technologies are used. First explanation can lie in methodical features of artificial fertilization. Extracorporal fertilization implies hormone injections, which stimulate ovulation. Gonadotropins possibly accelerate maturation of ovules, which are still during genomic imprinting process. Sometimes ovules are cultivated in a nutrient medium before fertilization, and after fertilization fetuses grow in a nutrient medium before transplantation into organism of a mother. Medium’s composition and no signals from mother’s organism, which normally control fetus development, can also affect genomic imprinting, which takes place in both maturing ovule and developing fetus. Gamete and fetus cryopreservation can be another factor to affect genome marking process.

Second hypothesis says that during assisted reproduction events, which would never happen in nature, can take place. For instance, hormonal stimulation causes maturation of “irregular” ovules, which would have never appeared under normal conditions. Sperm cells can also have defects of genomic imprinting – such sperm shows reduced fertility and is not recommended for extracorporal fertilization. The last, but not the least important factor is delivery of sick children in sterile couples, predisposed to genomic imprinting diseases.

Today scientists and medics cannot boast an undivided opinion on ART and genomic imprinting diseases. Some think that sick “in vitro” children are born very rarely and cannot be the reason to avoid artificial fertilization. Their opponents consider known facts of genomic imprinting failures to be a drop in the ocean. Mankind knows too little, and risks of genomic imprinting faults are significant. The problem of safe extracorporal fertilization requires complex approach.

Source:
    Russian Science News

Kizilova Anna