Molecular genetic predictors and ovarian reserve in women with deep infiltrating endometriosis


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Abstract

Objective: To investigate molecular genetic predictors and ovarian reserve in patients with infiltrating extragenital endometriosis. Materials and methods: This is a case-control study including 70 patients of reproductive age with deep infiltrating endometriosis (study group) and 50 fertile women (control group). All patients underwent testing for ovarian reserve. The molecular genetic analysis included testing for polymorphic variants of genes encoding proteins involved in the regulation of apoptosis [C-KIT: 2600 G>A, KITLG: 80441 C>T, TP53: Ex4+119 G>C (Arg72Pro)] and angiogenesis ((VEGF-A: +12143 C>A, VEGF-A: -2578 C>A, VEGF-A: -634 G>C, VEGF-A: +936 C>T). Results: The AMH level was significantly lower in patients with deep infiltrating endometriosis [2.4 (2.0) ng/ ml] than in the control group [3.8 (3.2) ng/ml], p<0.05. Antral follicle counts were also significantly lower in women in the study group [8.3 (4.5)] than in the control group [11.8 (4.1)], p<0.001. Women in the study group had a statistically significantly higher frequency of the polymorphic allele Ex4+119 G>C of the TP53 gene [OR 2.43 (95% CI1.12; 5.27)], p<0.03. Carriage of the polymorphic allele +12143 C>A of the VEGF-A gene in a homo- or heterozygous state increases the risk of deep infiltrating endometriosis [OR 2.18 (95% CI 1.03; 4.61)], p<0.05. Trilocus model constructed by multivariate analysis suggested the involvement of a combination of single nucleotide polymorphisms of genes regulating apoptosis (C-KIT: 2600 G>A, TP53: Ex4+119 G>C) and angiogenesis (VEGF-A: -2578 C>A) in the pathogenesis of endometriosis. Conclusion: Deep infiltrating endometriosis without visible affection of the ovaries may be associated with a significant decline in ovarian reserve. Dysregulation of apoptosis and angiogenesis in deep infiltrating endometriosis may be a critical mechanism undelaying diminished ovarian reserve due to the premature activation of primordial follicles and their early depletion.

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About the authors

Oxana A. Melkozerova

Ural Research Institute of Maternity and Child Care, Ministry of Health of Russia

Email: abolmedi@mail.ru
Dr. Med. Sci., Deputy of Director for Science

Ekaterina O. Okulova

Ural Research Institute of Maternity and Child Care, Ministry of Health of Russia

Email: cat93_07@mail.ru
PhD. Student of the Department of Reproductive Functions Preservation

Anna A. Mikhelson

Ural Research Institute of Maternity and Child Care, Ministry of Health of Russia

Email: annjukach@list.ru
Dr. Med. Sci., Head of the Department of Reproductive Functions Preservation, Head of the Department of Gynecology

Tatyana B. Tretyakova

Ural Research Institute of Maternity and Child Care, Ministry of Health of Russia

Email: tbtretyakova@yandex.ru
Ph.D., Senior Researcher at the Department of Biochemical Research with Genetics Group, Head of the Genetics Laboratory

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