Cenomorphics for IVF
Scientists have found out how to increase the chances of successful in vitro fertilization
Alexandra Borodkin, Indicator
Russian scientists have determined that aging of endometrial stromal cells — lining of the uterine cavity — can prevent the embryo from attaching to the organ wall during pregnancy, which can lead to infertility. The reason is that these cells stop responding to hormonal signals and produce prolactin and other factors necessary for implantation. However, the authors proved that such an effect can be avoided by using special preparations — cenomorphics, small molecules that, unlike senolytics, do not destroy, but suppress aging phenotypes and, when used in clinical practice, will help increase the chances of successful in vitro fertilization. The results of the study, supported by a grant from the Russian Science Foundation (RNF), are published in the journal Human Reproduction (Deryabin, Borodkina, Stromal cell senescence contributes to enhanced endometrial decidualization and defective interaction with trophoblast cells).
The cells of the endometrium — the tissue lining the uterine cavity — undergo significant changes during the menstrual cycle. Actively dividing stromal (stem) cells turn into mature decidual cells, which ensure the proper attachment of the embryo to the uterine wall and secrete substances necessary for its subsequent development, including the female sex hormone prolactin. This process is called decidualization, and its violation leads to infertility.
Scientists from the Institute of Cytology of the Russian Academy of Sciences (St. Petersburg) have confirmed that in the process of aging of endometrial stromal cells (SCE), the process of their transformation into decidual cells is disrupted. This, in turn, prevents the implantation of the embryo and the further course of pregnancy. With aging, cells lose their ability to divide, increase in size, they are characterized by damage to DNA, disorders in the work of genes, an increase in the level of reactive oxygen species. Biologists compared the properties of young and old CSE obtained from donors in vitro, that is, outside the body. First of all, the authors were interested in how these cells react to treatment with the hormones progesterone and estrogen, since they are the ones that give the signal to stromal cells to decidualization.
It turned out that the old stromal cells reacted much worse to the sex hormones acting on them, which reduced their ability to differentiate into decidual ones. They also had less active marker genes for this transformation. As a result, such cells secreted about 1.5 times less prolactin than young ones, which created unfavorable conditions for implantation. By conducting an experiment with model blastocysts simulating an embryo at an early stage of development, scientists were able to demonstrate that aging CES can indeed prevent the embryo from fully immersing into the endometrial stroma.
In addition, aging SCES interfered with the decidualization of neighboring young cells in direct contact with them, as well as due to the release of special substances into the medium. However, additional treatment with cenomorphics — drugs that reduce the signs of aging — helped restore the ability of cells to perceive hormonal signals. With the help of metformin, it was possible to stop the negative effects of aging SCES on neighboring young cells. Like this drug, rapamycin increased the penetration of blastocyst-like structures into the layer formed by the line with aging cells, thus improving implantation by about 1.4 times.
"Exposure to aging endometrial stromal cells with the help of special compounds — cenomorphs — contributed to the restoration of the receptive properties of the endometrium. With subsequent clinical adaptation, the approach based on the use of cenomorphs can be used to increase the efficiency of in vitro fertilization (IVF) cycles and reduce the percentage of women suffering from multiple unsuccessful implantations, as well as to solve a number of other problems of female reproduction," says Alexandra Borodkina, PhD, Senior Researcher, Head of the RNF grant project. Researcher, Head of the scientific group of mechanisms of cellular aging of the Laboratory of Intracellular Signaling of the Institute of Cytology of the Russian Academy of Sciences.
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