Number Of Ribosomes Research Articles

Single-cell heterogeneity in ribosome content and the consequences for the growth laws.

Across species and environments, the ribosome content of cell populations correlates with population growth rate. The robustness and universality of this correlation have led to its classification as a "growth law." This law has fueled theories about how evolution selects for microbial organisms that maximize their growth rate based on nutrient availability, and it has informed models about how individual cells regulate their growth rates and ribosomal content. However, due to methodological limitations, this growth law has rarely been studied at the level of individual cells. While populations of fast-growing cells tend to have more ribosomes than populations of slow-growing cells, it is unclear whether individual cells tightly regulate their ribosome content to match their environment. Here, we employ recent groundbreaking single-cell RNA sequencing techniques to study this growth law at the single-cell level in two different microbes, S. cerevisiae (a single-celled yeast and eukaryote) and B. subtilis (a bacterium and prokaryote). In both species, we observe significant variation in the ribosomal content of single cells that is not predictive of growth rate. Fast-growing populations include cells exhibiting transcriptional signatures of slow growth and stress, as do cells with the highest ribosome content we survey. Broadening our focus to non-ribosomal transcripts reveals subpopulations of cells in unique transcriptional states suggestive that they have evolved to do things other than maximize their rate of growth. Overall, these results indicate that single-cell ribosome levels are not finely tuned to match population growth rates or nutrient availability and cannot be predicted by a Gaussian process model that assumes measurements are sampled from a normal distribution centered on the population average. This work encourages the expansion of growth law and other models that predict how growth rates are regulated or how they evolve to consider single-cell heterogeneity. To this end, we provide extensive data and analysis of ribosomal and transcriptomic variation across thousands of single cells from multiple conditions, replicates, and species.

Ribosome Assembly and Repair.

Ribosomes synthesize protein in all cells. Maintaining both the correct number and composition of ribosomes is critical for protein homeostasis. To address this challenge, cells have evolved intricate quality control mechanisms during assembly to ensure that only correctly matured ribosomes are released into the translating pool. However, these assembly-associated quality control mechanisms do not deal with damage that arises during the ribosomes' exceptionally long lifetimes and might equally compromise their function or lead to reduced ribosome numbers. Recent research has revealed that ribosomes with damaged ribosomal proteins can be repaired by the release of the damaged protein, thereby ensuring ribosome integrity at a fraction of the energetic cost of producing new ribosomes, appropriate for stress conditions. In this article, we cover the types of ribosome damage known so far, and then we review the known repair mechanisms before surveying the literature for possible additional instances of repair.

Quantitative proteomics reveals the mechanism of endoplasmic reticulum stress-mediated pulmonary fibrosis in mice

Pulmonary fibrosis is a progressive disease that can lead to respiratory failure. Many types of cells are involved in the progression of pulmonary fibrosis. This study utilized quantitative proteomics to investigate the mechanism of TGF-β-induced fibrosis-like changes in mouse epithelial cells. Our findings revealed that TGF-β significantly impacted biological processes related to the endoplasmic reticulum, mitochondrion, and ribonucleoprotein complex. Pull-down assay coupled with proteomics identified 114 proteins that may directly interact with TGF-β, and their functions were related to mitochondria, translation, ubiquitin ligase conjugation, mRNA processing, and actin binding. Among them, 17 molecules were also found in different expression proteins (DEPs) of quantitative proteomic, such as H1F0, MED21, SDF2L1, DAD1, and TMX1. Additionally, TGF-β decreased the folded structure and the number of ribosomes in the endoplasmic reticulum and increased the expression of key proteins in the unfolded protein response, including HRD1, PERK, and ERN1. Overall, our study suggested that TGF-β induced fibrotic changes in mouse lung epithelial cells by ER stress and initiated the unfolded protein response through the PRKCSH/IRE1 and PERK/GADD34/CHOP signaling pathways.

Conservative deep neural networks for modeling competition of ribosomes with extended length

We develop a network model that combines several ribosome flow models with extended objects (RFMEO) competing for the finite pool of ribosomes. This alleviates the need to systematically coarse-grain the mRNA molecules. The dynamics of the network is described by a system of non-linear ordinary differential equations. It is shown that the network always converges to a steady state for a fixed number of ribosomes. Our analysis shows that increasing any of the transition rates along an RFMEO increases its output rate and either the output rates of the other RFMEOs all increase or all decrease. Simulations also demonstrate a counterintuitive result that increasing the ribosomal footprint may sometimes lead to an increase in the network production rate. Next, we propose a conservative deep neural network (CDNN) framework to approximate the solution of the network. The proposed loss function also incorporates the term satisfying the first integral property of the network. Point-wise comparison of the solutions by CDNN is in good agreement with the Runge–Kutta based numerical solution. Also, the CDNN framework offers a closed-form solution of the RFMEONP as a function of free parameters, thus allowing evaluation of the solution at any parameter value without again simulating the system.

Understanding the regulation of protein synthesis under stress conditions

Protein synthesis regulation primarily occurs at translation initiation, the first step of gene translation. However, the regulation of translation initiation under various conditions is not fully understood. Specifically, the reason why protein production from certain mRNAs remains resistant to stress while others do not show such resilience. Moreover, why is protein production enhanced from a few transcripts under stress conditions, whereas it is decreased in the majority of transcripts? We address them by developing a Monte Carlo simulation model of protein synthesis and ribosome scanning. We find that mRNAs with strong Kozak contexts exhibit minimal reduction in translation initiation rate under stress conditions. Moreover, these transcripts exhibit even greater resilience to stress when the scanning speed of 43S ribosome subunit is slow, albeit at the cost of reduced initiation rate. This implies a trade-off between initiation rate and the ability of mRNA to withstand stress. We also show that mRNAs featuring an upstream ORF can act as a regulatory switch. This switch elevates protein production from the main ORF under stress conditions; however, minimal to no proteins are produced under the normal condition. Because, in stress, a larger fraction of 43S ribosomes bypasses the upstream ORF due to its weak Kozak context. This, in turn, increases the number of scanning ribosomes reaching the main ORF, whose strong Kozak context can convert them into 80S ribosomes, even under stress conditions. This switching allows an efficient use of cellular resources by producing proteins when they are required. Thus, our computational study provides valuable insights into our understanding of stress-responsive translation-initiation.

Calibrated ribosome profiling assesses the dynamics of ribosomal flux on transcripts

Ribosome profiling, which is based on deep sequencing of ribosome footprints, has served as a powerful tool for elucidating the regulatory mechanism of protein synthesis. However, the current method has substantial issues: contamination by rRNAs and the lack of appropriate methods to measure ribosome numbers in transcripts. Here, we overcome these hurdles through the development of “Ribo-FilterOut”, which is based on the separation of footprints from ribosome subunits by ultrafiltration, and “Ribo-Calibration”, which relies on external spike-ins of stoichiometrically defined mRNA-ribosome complexes. A combination of these approaches estimates the number of ribosomes on a transcript, the translation initiation rate, and the overall number of translation events before its decay, all in a genome-wide manner. Moreover, our method reveals the allocation of ribosomes under heat shock stress, during aging, and across cell types. Our strategy of modified ribosome profiling measures kinetic and stoichiometric parameters of cellular translation across the transcriptome.

Physiological, biochemical, and global transcriptomic and metabolomic analyses of the effect of the antifungal compound isobavachalcone on Botrytis cinerea on cherry tomatoes

Botrytis cinerea is a major postharvest pathogen on cherry tomato (Solanum lycopersicum). In this study, isobavachalcone (IBC) exhibited inhibitory activity against fungus B. cinerea in vitro and in vivo. Morphological and ultrastructural observations were conducted revealing that IBC caused significant changes in B. cinerea, including rupturing of the cell membrane, loosening of the cell wall, swelling of mitochondria, and massive reductions in the number of ribosomes. Physiological and biochemical analyses confirmed that IBC increased the permeability of the cell wall and membrane which had led to decrease in mitochondrial membrane potential (MMP), while significant increase in reactive oxygen species (ROS) level. According to transcriptomic and metabolomic analysis, IBC inhibited the expression of chitin deacetylase (CDA), glucan 1,3-beta-glucosidase (EXG), and squalene monooxygenase (ERG1) genes, which may result in the degradation of cell wall and membrane components, ultimately increasing cell permeability. IBC also interfered with the expression of cytochrome P450 (CYP102A) and cytochrome-b5 reductase (CYB5R) genes, which had a negative impact on mitochondrial energy metabolism. Additionally, the structure of the ribosomal large subunit and small subunit were altered by IBC, thus, interfering with translation initiation and polypeptide extension. These results provide an effective alternative approach against B. cinerea on cherry tomato.

Removal of the large inverted repeat from the plastid genome reveals gene dosage effects and leads to increased genome copy number

The chloroplast genomes of most plants and algae contain a large inverted repeat (IR) region that separates two single-copy regions and harbours the ribosomal RNA operon. We have addressed the functional importance of the IR region by removing an entire copy of the 25.3-kb IR from the tobacco plastid genome. Using plastid transformation and subsequent selectable marker gene elimination, we precisely excised the IR, thus generating plants with a substantially reduced plastid genome size. We show that the lack of the IR results in a mildly reduced plastid ribosome number, suggesting a gene dosage benefit from the duplicated presence of the ribosomal RNA operon. Moreover, the IR deletion plants contain an increased number of plastid genomes, suggesting that genome copy number is regulated by measuring total plastid DNA content rather than by counting genomes. Together, our findings (1) demonstrate that the IR can enhance the translation capacity of the plastid, (2) reveal the relationship between genome size and genome copy number, and (3) provide a simplified plastid genome structure that will facilitate future synthetic biology applications.

Kinetics of programmed and spontaneous ribosome sliding along the mRNA.

The ribosome can slide along mRNA without establishing codon-anticodon interactions. This movement can be regulated (programmed) by the elements encoded in the mRNA, as observed in bypassing of non-coding gap in gene 60 of bacteriophage T4, or occur spontaneously, such as during traversal by the 70S ribosome of the 3'UTRs or upon re-initiation on bacterial polycistronic genes. In this study, we investigate the kinetic mechanism underlying the programmed and spontaneous ribosome sliding. We show that the translation rate of gene 60 mRNA decreases as the ribosome approaches the take-off site, especially when the KKYK regulatory sequence in the nascent peptide reaches the constriction site in the ribosome exit tunnel. However, efficiency of bypassing increases when the ribosome traverses the gap quickly. With the non-coding gap exceeding the natural 50 nt, the processivity of sliding remains high up to 56 nt, but drops sharply beyond that due to the loss of mRNA elements support. Sliding efficiency is temperature-dependent; while temperature regulates the number of ribosomes initiating programmed bypassing, traversing the long gaps becomes increasingly unfavorable at lower temperatures. This data offers novel insights into the kinetic determinants of programmed and spontaneous ribosome sliding along the mRNA.

FMRP regulation of aggrecan mRNA translation controls perineuronal net development.

Perineuronal nets (PNNs) are mesh-like structures on the surfaces of parvalbumin-expressing inhibitory and other neurons, and consist of proteoglycans such as aggrecan, brevican, and neurocan. PNNs regulate the Excitatory/Inhibitory (E/I) balance in the brain and are formed at the closure of critical periods of plasticity during development. PNN formation is disrupted in Fragile X Syndrome, which is caused by silencing of the fragile X messenger ribonucleoprotein 1 (Fmr1) gene and loss of its protein product FMRP. FXS is characterized by impaired synaptic plasticity resulting in neuronal hyperexcitability and E/I imbalance. Here, we investigate how PNN formation is altered in FXS. PNNs are reduced in Fmr1 KO mouse brain when examined by staining for the lectin Wisteria floribunda agglutin (WFA) and aggrecan. Examination of PNNs by WFA staining at P14 and P42 in the hippocampus, somatosensory cortex, and retrosplenial cortex shows that they were reduced in these brain regions at P14 but mostly less so at P42 in Fmr1 KO mice. However, some differential FMRP regulation of PNN development in these brain regions persists, perhaps caused by asynchrony in PNN development between brain regions in wild-type animals. During development, aggrecan PNN levels in the brain were reduced in all brain regions in Fmr1 KO mice. Aggrecan mRNA levels were unchanged at these times, suggesting that FMRP is normally an activator of aggrecan mRNA translation. This hypothesis is buttressed by the observations that FMRP binds aggrecan mRNA and that ribosome profiling data show that aggrecan mRNA is associated with reduced numbers of ribosomes in Fmr1 KO mouse brain, indicating reduced translational efficiency. Moreover, aggrecan mRNA poly(A) tail length is also reduced in Fmr1 KO mouse brain, suggesting a relationship between polyadenylation and translational control. We propose a model where FMRP modulates PNN formation through translational up-regulation of aggrecan mRNA polyadenylation and translation.

Workability of mRNA Sequencing for Predicting Protein Abundance.

Transcriptomics methods (RNA-Seq, PCR) today are more routine and reproducible than proteomics methods, i.e., both mass spectrometry and immunochemical analysis. For this reason, most scientific studies are limited to assessing the level of mRNA content. At the same time, protein content (and its post-translational status) largely determines the cell's state and behavior. Such a forced extrapolation of conclusions from the transcriptome to the proteome often seems unjustified. The ratios of "transcript-protein" pairs can vary by several orders of magnitude for different genes. As a rule, the correlation coefficient between transcriptome-proteome levels for different tissues does not exceed 0.3-0.5. Several characteristics determine the ratio between the content of mRNA and protein: among them, the rate of movement of the ribosome along the mRNA and the number of free ribosomes in the cell, the availability of tRNA, the secondary structure, and the localization of the transcript. The technical features of the experimental methods also significantly influence the levels of the transcript and protein of the corresponding gene on the outcome of the comparison. Given the above biological features and the performance of experimental and bioinformatic approaches, one may develop various models to predict proteomic profiles based on transcriptomic data. This review is devoted to the ability of RNA sequencing methods for protein abundance prediction.

Bet-hedging: Bacterial ribosome dynamics during growth transitions

It is known that bacteria reduce their ribosome numbers during nutrient starvation. New research shows that this regulation leads to the formation of two subpopulations with distinct ribosomal RNA levels. The distinct levels affect the growth recovery when nutrients become available, suggesting a possible bet-hedging strategy.

Physical modeling of ribosomes along messenger RNA: Estimating kinetic parameters from ribosome profiling experiments using a ballistic model.

Gene expression is the synthesis of proteins from the information encoded on DNA. One of the two main steps of gene expression is the translation of messenger RNA (mRNA) into polypeptide sequences of amino acids. Here, by taking into account mRNA degradation, we model the motion of ribosomes along mRNA with a ballistic model where particles advance along a filament without excluded volume interactions. Unidirectional models of transport have previously been used to fit the average density of ribosomes obtained by the experimental ribo-sequencing (Ribo-seq) technique in order to obtain the kinetic rates. The degradation rate is not, however, accounted for and experimental data from different experiments are needed to have enough parameters for the fit. Here, we propose an entirely novel experimental setup and theoretical framework consisting in splitting the mRNAs into categories depending on the number of ribosomes from one to four. We solve analytically the ballistic model for a fixed number of ribosomes per mRNA, study the different regimes of degradation, and propose a criterion for the quality of the inverse fit. The proposed method provides a high sensitivity to the mRNA degradation rate. The additional equations coming from using the monosome (single ribosome) and polysome (arbitrary number) ribo-seq profiles enable us to determine all the kinetic rates in terms of the experimentally accessible mRNA degradation rate.

Growth-rate dependency of ribosome abundance and translation elongation rate in Corynebacterium glutamicum differs from that in Escherichia coli

Bacterial growth rate (µ) depends on the protein synthesis capacity of the cell and thus on the number of active ribosomes and their translation elongation rate. The relationship between these fundamental growth parameters have only been described for few bacterial species, in particular Escherichia coli. Here, we analyse the growth-rate dependency of ribosome abundance and translation elongation rate for Corynebacterium glutamicum, a gram-positive model species differing from E. coli by a lower growth temperature optimum and a lower maximal growth rate. We show that, unlike in E. coli, there is little change in ribosome abundance for µ <0.4 h−1 in C. glutamicum and the fraction of active ribosomes is kept above 70% while the translation elongation rate declines 5-fold. Mathematical modelling indicates that the decrease in the translation elongation rate can be explained by a depletion of translation precursors.

CHANGES IN THE CEREBRAL CORTEX NEURON ULTRASTRUCTURE IN RATS WITH PARTIAL CEREBRAL ISCHEMIA

The ultrastructural characteristics of neuronal organelles are significant indicators of brain damage under ischemic exposure, which necessitates the study of changes in the ultrastructure of brain neurons.&#x0D; The aim of the study was to examine the disorders of brain neurons under its partial ischemia at the ultrastructural level using an experimental model.&#x0D; Materials and Methods. The experimental group included 12 male rats weighing 260±20 g, the control group consisted of 6 falsely operated male rats of the same weight. Partial cerebral ischemia (PCI) was modeled by right common carotid artery ligation. The material was taken 1 hour after the operation.&#x0D; Results. The study showed that the size and shape of the mitochondria of neurons of the parietal cortex and the hippocampus in PCI rats did not differ from those of the control group (p&gt;0.05), except for a smaller number of cristae per unit area in the mitochondria of parietal cortex neurons (by 18 %, p&lt;0.05).&#x0D; The size and shape of the Golgi complex and lysosomes did not differ in the groups either. However, there was an increase in the number of free ribosomes in the cytoplasm of neurons in the parietal cortex and hippocampus of PCI rats, by 58 % and 54 %, respectively (p&lt;0.05).&#x0D; The ratio of fixed and free ribosomes in control rats decreased from 3.4 to 0.8 in the parietal cortex (p&lt;0.05) and from 2.33 to 0.7 in the hippocampus (p&lt;0.05).&#x0D; Conclusions. In general, the neuron ultrastructure in PCI rats was similar to that in the control group, which might be due to blood flow compensation in the circle of Willis. An increase in the number of free ribosomes is a sign of deranged protein biosynthesis in neurons. A decrease in the number of mitochondrial cristae in neurons in the parietal cortex indicates energy deficiency.

Relationship of Protein Synthesis to mRNA Levels in the Muscle of Chicks under Various Nutritional Conditions

The relationship between the rate of protein synthesis and the level of messenger RNA (mRNA) in the breast muscle (pectoralis major) was studied to examine the mechanisms regulating muscle protein synthesis in chicks under various nutritional conditions. The fractional synthesis rate (FSR) of protein was measured by a large-dose injection of L-[4-3H]phenylalanine. Poly(U)-Sepharose 4B affinity chromatography was used to extract Poly(A)+ RNA as mRNA. The first study examined the effect of dietary protein levels (0–60%) on protein synthesis rate and the contents of mRNA and total RNA. The fractional synthesis rate increased with increasing dietary protein levels from 0 to 20%. When chicks were fed high protein diets (40 and 60% of dietary protein), both the FSR and absolute synthesis rate (ASR) of protein were reduced compared with the 20% protein group. Multiple regression analysis indicated that for graded dietary protein levels below the dietary protein requirement, the response of muscle protein synthesis is largely regulated by variation in the ASR per unit RNA (the efficiency of RNA in synthesizing protein). At dietary protein levels above 20%, synthesis rates are also related to changes in the RNA:mRNA ratio (ribosome number relative to mRNA), the mRNA:DNA ratio (mRNA availability) and the DNA:protein ratio (DNA concentration). When chicks were food deprived for 2 d, FSR was reduced to about half that of well-fed controls. Upon refeeding of these chicks with the control diet, the FSR returned to the normal level within 0.5 h. When food-deprived chicks were refed with protein, carbohydrate or fat alone, the FSR returned to the control level within 0.5 h after consumption of each nutrient. The increase in muscle protein synthesis of unfed chicks following refeeding of various nutrients was explained by an increased ASR per unit RNA. Our results suggest that nutrient intake can change muscle protein synthesis rates in chicks largely by altering the ASR per unit RNA, in some cases associated also with changes in the levels of RNA, mRNA and DNA.

Hepatic ribosomal protein S6 (Rps6) insufficiency results in failed bile duct development and loss of hepatocyte viability; a ribosomopathy-like phenotype that is partially p53-dependent

Defective ribosome biogenesis (RiBi) underlies a group of clinically diverse human diseases collectively known as the ribosomopathies, core manifestations of which include cytopenias and developmental abnormalities that are believed to stem primarily from an inability to synthesize adequate numbers of ribosomes and concomitant activation of p53. The importance of a correctly functioning RiBi machinery for maintaining tissue homeostasis is illustrated by the observation that, despite having a paucity of certain cell types in early life, ribosomopathy patients have an increased risk for developing cancer later in life. This suggests that hypoproliferative states trigger adaptive responses that can, over time, become maladaptive and inadvertently drive unchecked hyperproliferation and predispose to cancer. Here we describe an experimentally induced ribosomopathy in the mouse and show that a normal level of hepatic ribosomal protein S6 (Rps6) is required for proper bile duct development and preservation of hepatocyte viability and that its insufficiency later promotes overgrowth and predisposes to liver cancer which is accelerated in the absence of the tumor-suppressor PTEN. We also show that the overexpression of c-Myc in the liver ameliorates, while expression of a mutant hyperstable form of p53 partially recapitulates specific aspects of the hepatopathies induced by Rps6 deletion. Surprisingly, co-deletion of p53 in the Rps6-deficient background fails to restore biliary development or significantly improve hepatic function. This study not only reveals a previously unappreciated dependence of the developing liver on adequate levels of Rps6 and exquisitely controlled p53 signaling, but suggests that the increased cancer risk in ribosomopathy patients may, in part, stem from an inability to preserve normal tissue homeostasis in the face of chronic injury and regeneration.

Circular RNA circTRPS1-2 inhibits the proliferation and migration of esophageal squamous cell carcinoma by reducing the production of ribosomes

Circular RNAs play important roles in many cancers, including esophageal squamous cell carcinoma (ESCC), but the precise functions of most circular RNAs are poorly understood. Here we detected significant downregulation of circTRPS1-2 in ESCC based on high-throughput sequencing of three pairs of ESCC tissue and adjacent normal tissue, followed by PCR validation with another 30 tissue pairs. Patients with ESCC whose circTRPS1-2 expression was below the median level for the sample showed significantly shorter median overall survival (13 months) than patients whose circTRPS1-2 expression was above the median (36 months). Overexpressing circTRPS1-2 in the human ESCC cell lines K150 and E109, which express low endogenous levels of circTRPS1-2, inhibited cell proliferation and migration. Conversely, knocking down circTRPS1-2 using short interfering RNA promoted cell proliferation and migration. Similar results were observed in mice bearing K150 xenografts in which circTRPS1-2 was overexpressed or knocked down. Several ribosomal proteins co-immunoprecipitated with circTRPS1-2 from K150 cells in culture, and K150 cells overexpressing circTRPS1-2 showed reduced numbers of ribosomes by A260 absorbance measure and electron microscopy. Our results suggest that circTRPS1-2 can inhibit ESCC proliferation and migration by reducing the production of ribosomes, establishing its potential usefulness in ESCC treatment and prediction of prognosis.

Deficiency of ribosomal protein S26, which is mutated in a subset of patients with Diamond Blackfan anemia, impairs erythroid differentiation.

Introduction: Diamond Blackfan anemia (DBA) is a rare congenital disease characterized by defective maturation of the erythroid progenitors in the bone marrow, for which treatment involves steroids, chronic transfusions, or hematopoietic stem cells transplantation. Diamond Blackfan anemia is caused by defective ribosome biogenesis due to heterozygous pathogenic variants in one of 19 ribosomal protein (RP) genes. The decreased number of functional ribosomes leads to the activation of pro-apoptotic pathways and to the reduced translation of key genes for erythropoiesis. Results and discussion: Here we characterized the phenotype of RPS26-deficiency in a cell line derived from human umbilical cord blood erythroid progenitors (HUDEP-1 cells). This model recapitulates cellular hallmarks of Diamond Blackfan anemia including: imbalanced production of ribosomal RNAs, upregulation of pro-apoptotic genes and reduced viability, and shows increased levels of intracellular calcium. Evaluation of the expression of erythroid markers revealed the impairment of erythroid differentiation in RPS26-silenced cells compared to control cells. Conclusions: In conclusion, for the first time we assessed the effect of RPS26 deficiency in a human erythroid progenitor cell line and demonstrated that these cells can be used as a scalable model system to study aspects of DBA pathophysiology that have been refractory to detailed investigation because of the paucity of specific cell types affected in this disorder.

The effect of gestataional hypertension on the ultrastructural structure of the placenta

The objective: to study pathological changes and compensatory-adaptive reactions in the structural and ultrastructural components of the placental barrier in pregnant women with gestational arterial hypertension, who received magnesium preparations. Materials and methods. 100 patients with gestational hypertension were examined. The presence of magnesium deficiency in these women was determined by the results of our questionnaires.Pathomorphological and electronic microscopic examination of 32 placentas of patients with gestational hypertension was carried out. 12 placentas of them were from pregnant women who received the proposed management of pregnancy, which included magnesium drugs (I group), and 11 placentas – from patients with risk of preeclampsia, who were observed with the use of standard approaches of pregnancy for women with the risk of preeclampsia (II group). Control group included the results of pathomorphological and electronic microscopic study of 9 placentas from healthy women.Results. Placental of women with gestational hypertension have structural features, which is manifested by the mosaic change of placental barrier in the form of uneven circulatory disorders with hemorrhages and stasis (at the ultrastructural level) in the fetal microvessels of the villi, reducing the placental functional area (rapprochement of the villi), presence of stromal sclerosis villi, foci of pathological immaturity, increase in calcium salts (mineral dystrophy) on the background of compensatory reactions. Electronic microscopic study of the placentas in the I group revealed an increase in the compensatory-adaptive reactions of the placenta – thinning of the placental barrier, activation of cytotrophoblast cells in the placental barrier, increase the number of syncytiocapillary membranes in terminal villi with syncytiotrophoblast organic activation, increase in the number of ribosomes, the appearance of orthodox configuration of mitochondria, increasing the number of capillary membranes and thinning of syncytia, reducing the number of sludge phenomena in microvessels, which leads to an increase in the possibility of nutrient transfer from mother to fetus, etc.Conclusions. The use of the proposed therapy, which involves magnesium, diosmin and others substances, leads to a significant decrease in the frequency of detection of pathological changes in structural and ultrastructural components of the placental barrier and increased compensatory-adaptive reactions which can be considered the result of the positive impact of the proposed therapy on the placental ultrastructural elements in women with risk of preeclampsia.