Doctoral defence: Marina Loid "Molecular and cellular determinants of healthy receptive and aged endometrium"

On November 27th 2024 Marina Loid will defend her thesis "Molecular and cellular determinants of healthy receptive and aged endometrium".

Supervisors:
Professor Andres Salumets, University of Tartu
Associate professor Kaarel Krjutškov, University of Tartu
Associate professor Masoud Zamani Esteki, University of Maastricht (Netherlands)

Opponent:
dr Patricia Diaz-Gimeno, IVI Foundation-IIS la Fe (Spain)

Summary:
Infertility affects 15% of all couples, having a significant impact on their quality of life. In the modern world of aging mankind, where the maternal age is constantly increasing, age-related infertility is an important medical problem. The development of in vitro fertilisation (IVF) together with rapid development of gamete and embryo freezing technologies has made it possible to have children even in the 50s. To assess the response to hormone therapy and predict the optimal day for embryo transfer, receptivity testing of uterine lining (endometrium) using ultrasonic, histological and molecular markers, is applied. Previous studies have conflicting results on the clinical efficacy of transcriptomic endometrial receptivity tests. In addition, IVF success rate is lower among women over 40, even with the use of donor oocytes from younger women or following pre-implantation genetic testing of embryos.

The aims of this work were to 1) test how the cellular composition of endometrium changes during the menstrual cycle and affects the gene expression profile of the whole endometrial tissue sample; 2) identify the endometrial markers from the woman's blood and investigate the effect of advanced age on the endometrial gene expression, and 3) assess the effect of woman’s age on the gene expression profile of endometrial tissue.

A novel deconvolution analysis of the tissue unravelled cellular changes in the mid-secretory phase and allowed us to tailor the gene expression profile of transcriptomic endometrial test. While no miRNA markers were found in the blood sample, we identified new endometrial regulating RNA molecules associated with endometrial receptivity. Deconvolution of the gene expression profile of the endometrium of advanced maternal age women revealed a higher proportion of a rare epithelial cell population, the multiciliated cells, and the higher expression of cell senescence marker p16 in the endometrial epithelium in the advanced age group, which may be related to the chronic changes in endometrium concurrent with woman’s age.

In conclusion, the results of this work point that transcriptomic tests for endometrial testing must account for the cellular composition in the endometrium during transition to the receptive state, and the success of infertility treatment in older women could be substantially improved and made safer using the molecular and cellular markers of the aging endometrium.

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