Genetic association of the xenobiotic biotransformation system with the risk of death of the gestational sac in primigravida women living in an industrial city

Introduction. Every second conception in the population ends in failure, in 20% of the cases the cause is a non-developing pregnancy. In the overall structure of early reproductive losses, missed miscarriage accounts for 80%. The development of this pathology is influenced by both endogenous and exogenous factors. Exogenous factors with a teratogenic effect lead to the occurrence of mutations and the formation of an abnormal embryo, which is poorly predicted. The peculiarities of the biotransformation system of xenobiotics of the maternal organism directly affect the severity of the impact of these factors on the embryo.

Materials and methods. A survey of eighty six young primigravida women living in Novokuznetsk was conducted. 33 of them were diagnosed with the gestational sac death, 53 women had a standard developed pregnancy. Variants of the GSTM1 and GSTT1 genes of the second phase of the xenobiotic biotransformation system were determined in these groups by polymerase chain reaction.

Results. Novokuznetsk, a city with a critically high level of environmental pollution, has recorded a 20–fold increase in the number of missed miscarriages over the past 25 years. A statistically reliable association of deletion polymorphisms of the genes of the second phase of the xenobiotic biotransformation system with the death of the gestational sac — GSTM1 (χ² — 5.37; OR — 3.18) and GSTT1 (χ² — 10.85; OR — 16.64) was revealed, while the normal alleles were associated with a successful outcome of pregnancy — GSTM1 (χ² — 5.37; OR — 0.13) and GSTT1 (χ² — 10.85; OR — 0.06).

Limitations. The study was of a pilot nature, so it is advisable to increase the sample in the future.

Conclusion. The dependence between the activity of enzymes of the second phase of the xenobiotic biotransformation system and the increased risk of miscarriage of the first pregnancy in young women living in the conditions of ecological distress was revealed. The results of the study make it possible to predict possible pregnancy complications and elaborate algorithms for full-fledged pregravid preparation.

Compliance with ethical standards. The examination of patients corresponded to the ethical standards of the Bioethical Committee of the Research Institute for Complex Problems of Hygiene and Occupational Diseases, elaborated in accordance with the Declaration of Helsinki of the World Medical “Ethical Principles for Medical Research Involving Human Subjects” as amended 2013 and the “Rules of Proper Clinical Practice” approved by Order of the Ministry of Health of the Russian Federation dated April 1, 2016 N 200n. Each participant of the study gave informed voluntary written consent to take part in the study and publish personal medical information in anonymized form in the journal “Hygiene and Sanitation”.

Contribution:
Gulyaeva O.N. — concept and design of research, collection and processing of material, statistical processing, editing;
Kazitskaya A.S. — collection and processing of material;
Ulanova E.V. — collection and processing of material, editing;
Matoshin S.V. — collection and processing of material;
Shramko S.V. — the concept and design of the study;
Zhukova A.G. — editing.
All authors are responsible for the integrity of all parts of the manuscript and approval of the manuscript final version.

Conflict of interest. The authors declare no conflict of interest.

Acknowledgement. The study had no sponsorship.

Received: December 15, 2024 / Revised: February 5, 2024 / Accepted: April 9 / Published: May 8, 2024