Maternal Organism Research Articles

Management of SARS-CoV-2 infection in pregnancy

The SARS-CoV-2 infection, which originated from a market in Wuhan, China, spread rapidly, so on March 11, 2020, the WHO decreed that the outbreak became a pandemic. Over 90% of people infected with SARS-CoV-2 are either asymptomatic or have mild symptoms. However, there are cases that develop severe forms of the disease, from acute respiratory distress syndrome to septic shock with multiorgan failure and exitus. However, reports of pregnant women diagnosed with Covid-19 are low. Changes in the maternal organism in pregnancy, including immunity, respiratory system and hypercoagulability, but also various comorbidities, could be a risk factor for pregnant women to develop complications associated with COVID-19, with increased morbidity and mortality compared to the general population. The effects of SARS-CoV-2 infection on pregnancy are not sufficiently understood, nor are the effects of pregnancy on disease progression. Although the existence of the virus has been shown in biological samples such as the placenta, umbilical cord, or amniotic fluid, the maternal and fetal effects of the virus are not well known. Recent studies confirm the possibility of intrauterine maternal-fetal transmission of the virus, but also of specific antibodies. The possibility of infection by breastfeeding is not yet sufficiently investigated. We looked for data on the treatment and prophylaxis of SARS-CoV-2 infection during pregnancy, as well as on the choice of the optimal birth pathway in these women. The aim of this paper was to conduct a systematic review of the literature on pregnancy and birth management in patients infected with SARS-CoV-2 that could lead to an improvement in the quality of their medical care.

Possible risk of fetal development of autism in pregnant women infected by SARS-CoV-2

Introduction. In March 2020, the World Health Organization (WHO) announced the emergence of a global pandemic, COVID-19. A disease triggered by the new coronavirus infection (SARS-CoV-2). More recent findings indicate that the gestational period makes the mother and her offspring more susceptible to the new coronavirus and the rapid progression to the critical stage of the disease. The maternal organism presents a certain degree of immunological and cardiorespiratory deficiency due to physiological adaptations to the gestational period and, consequently, if affected by prenatal infections caused by viruses, they lead to an exacerbated Maternal Immune Activation (MIA), thus contributing to alterations in maternal-fetal neurogenesis, fetal myelinization, and is directly involved in the pathogenesis of neurodevelopmental disorders in the offspring, especially autism. Objective. This study hypothesizes that maternal COVID-19 infections during pregnancy are a potential risk for the offspring to develop Autism Spectrum Disorder. Conclusion. The exposure to viral infectious agents during the gestational period leads to exacerbated maternal immune activation. It contributes to alterations in maternal-fetal neurogenesis and is directly involved in the pathogenesis of neurodevelopmental disorders, being correlated to the predisposition to affective and psychiatric disorders in the offspring. Therefore, greater attention should be given to the offspring of pregnant women infected by COVID-19, since prenatal infectious processes have a strong correlation with the prevalence of Autistic Spectrum Disorder in the offspring.

MiR-141-3p downregulation promotes tube formation, migration, invasion and inhibits apoptosis in hypoxia-induced human umbilical vein endothelial cells by targeting Notch2

Vascular endothelial cell damage is regarded as the carrier in the progression of the pathological changes of preeclampsia (PE) from the placenta to maternal organs. MicroRNA (miR)-141-3p was aberrantly expressed during PE pathogenesis. We investigated the role of miR-141-3p in regulating the biological behaviors of endothelial cells in PE. Human umbilical vein endothelial cells (HUVECs) were isolated from the human umbilical cords and cultured under hypoxia condition to establish PE models. The binding of miR-141-3p and Notch2 was confirmed by dual-luciferase reporter assay. HUVECs were transfected with miR-141-3p inhibitor and siRNA-Notch2. The viability, vascularization capability, migration, and invasion of HUVECs were evaluated by MTT, tube formation, and Transwell assays. Cell apoptosis was measured via flow cytometry. The expressions of miR-141-3p, Notch2, Bcl-2, Bax and cleaved caspase-3 were assessed by qRT-PCR or Western blot. MiR-141-3p expression was upregulated in the HUVECs isolated from PE tissues and hypoxia-induced HUVECs. Hypoxia treatment inhibited viability, tube formation, migration, and invasion, and promoted apoptosis in HUVECS, as well as increased Bax and cleaved caspase-3 expressions and decreased Bcl-2 expression. Downregulating miR-141-3p expression promoted viability, tube formation, migration and invasion, and inhibited apoptosis in HUVECs, counteracting the effect of hypoxia on HUVECs. MiR-141-3p directly targeted Notch2. Silencing Notch2 reversed the promoting effect of downregulated miR-141-3p expression on HUVECs. In conclusion, downregulating miR-141-3p expression during hypoxia promotes tube formation, migration, and invasion and inhibits apoptosis in HUVECs by targeting Notch2.

Changes in mRNA and protein levels of gonadotropin releasing hormone and receptor in ovine thymus, lymph node, spleen, and liver during early pregnancy

There exists maternal immunological modification in maternal immune organs during early pregnancy in mammals. Gonadotropin releasing hormone (GnRH) is widely distributed in vertebrate tissues, including immune organs. However, it is unclear that early pregnancy induces expression of GnRH and GnRH receptor (GnRHR) in ovine immune organs. The objective of this study was to explore the expression of GnRH and GnRHR in main immune organs (thymus, lymph node, spleen, and liver) during early pregnancy in sheep. Ovine thymus, lymph node, spleen and liver were sampled at day 16 of estrous cycle, and days 13, 16, and 25 of pregnancy. The expression of GnRH and GnRHR was detected through real-time quantitative PCR, Western blot and immunohistochemistry analysis. The results indicated that early pregnancy induced upregulation of mRNA and protein levels of GnRH and GnRHR in the maternal lymph node, spleen and liver, and mRNA and protein of GnRH in the maternal thymus, but mRNA and protein of GnRHR decreased in the maternal thymus during early pregnancy. In summary, the mRNA and protein levels of GnRH and GnRHR were changed in maternal thymus, lymph node, spleen and liver in a tissue specific manner during early pregnancy in sheep.

ПРЕНАТАЛЬНОЕ ВОЗДЕЙСТВИЕ СВИНЦА НА СТРУКТУРУ ПЕЧЕНИ НОВОРОЖДЕННЫХ КРЫС

The liver structure of the offspring of white rats was studied under conditions of the action of a low dose lead acetate (1 mg/kg of body weight) female during pregnancy. Histological, morphometric and informational analysis of the liver structures in the control and experiment in newborn rat was carried out. It has been shown that prenatal exposure to low doses of lead acetate does not cause significant damage to the liver structure of newborns. Lymphocytic infiltration in the portal area plethora of central vein, expansion of hemocapillaries were found. A statistically significant increase in the size of the nucleus of the hepatocytes, the number of foci of hematopoiesis in the parenchyma of liver, the expansion of hemocapillaries in the experiment compared with the control was established. The observed changes can be considered as a magnification of an adaptive response to the action of anthropogenic factors in the relationship between the fetus and the maternal organism.

Maternal and fetal outcomes of pregnancy in chronic kidney disease: diagnostic challenges, surveillance and treatment throughout the spectrum of kidney disease.

Pregnancy requires several physiological adaptations from the maternal organism, including modifications in the glomerular filtration rate and renal excretion of several products. Chronic kidney disease (CKD) can negatively affect these modifications and consequently is associated with several adverse maternal and fetal adverse outcomes (gestational hypertension, progression of renal disease, pre-eclampsia, fetal growth restriction, and preterm delivery). A multidisciplinary vigilance of these pregnancies is essential in order to avoid and/or control the harmful effects associated with this pathology. Dialysis and transplantation can decrease the risks of maternal and fetal complications, nonetheless, the rates of complications remain high comparing with a normal pregnancy. Several recent developments in this area have improved quality and efficacy of treatment of pregnant women with CKD. This article summarizes the most recent literature about CKD and pregnancy.

The outcomes of fetal cell microchimerism in the mother

The presence of small quantities of genetically heterogeneous cells in an organism is known as microchimerism. Fetal microchimerism is the presence of small quantities of fetal cells in the maternal system during and after pregnancy. Since these cells are semi-allogeneic in the mother's body, they have an impact on the mother's health. Recent studies suggest contradictory outcomes. Some suggest an involvement in autoimmune diseases and cancer. Others suggest involvement in tissue repair and wound healing. Fetal cells have been detected in maternal organs decades after pregnancy. It was found that these cells participate in the healing process post a chronic injury. In other cases, these cells initiate an immune response which may lead to the development of autoimmune diseases. Further, studies show that fetal cells have been discovered in the tumor microenvironment, either aiding in cancer development or eradicating the cancer cells. Here, I review the different outcomes that can occur in the female body because of fetal cell microchimerism. I discuss the presence of fetal cells in maternal organs such as the heart and the central nervous system organs and their involvement in disease development and tissue repair in the mother.

Evaluation of histochemical and molecular markers in the placenta of sows during pregnancy complicated by isoimmunization

It is known that the pathological course of pregnancy is associated with a disturbance in the interdependent “mother-fetus” complex and leads to specific clinical consequences at the molecular-cellular, tissue, organ, organismal and population levels of organization. In case of violation of placentation (placental barrier), a state of immune conflict occurs, characterized by an antigen-antibody reaction, carried out through the placenta (in relation to the fetus), or through colostrum after birth (in relation to the newborn offspring). Therefore, immunological relations at the population level should be considered both the consequences of the action of the maternal organism’s antigens on the fetus, and the effects of the allogeneic action of the fetus on the mother’s body. According to the results of the experiment, the placentas of 10 sows of Large White breed were used as the material, which showed signs of isoimmunization to the resulting offspring. For histological examination, immediately after delivery, pieces of placenta up to 0.5 cm thick were selected, which were fixed in a 10% aqueous solution of neutral formalin. The fixed material after wiring through alcohols of increasing concentration, xylene, xylene-paraffin, was poured into paraffin. The obtained preparations were stained with conventional methods-hematoxylin and eosin. d (fibrinoid masses).

Preeclampsia: inflammatory signature of decidual cells in early manifestation of disease

IntroductionPreeclampsia is a pregnancy-specific complication characterized by hypertension in combination with proteinuria and/or various manifestations of multiple organ failure. It is believed that etiology of preeclampsia lies in dysfunction of the placenta and disorder of the maternal-fetal interactions. In preeclampsia decidual membrane, the maternal part of the placenta which normally supports immunological tolerance of the maternal organism to the semi-allogeneic fetus, becomes a site of inflammation. MethodsThe aim of our study was to characterize the phenotype of decidual macrophages and plasma profiles in patients with late- and early-onset preeclampsia as compared with controls (n = 43). Decidual cells were obtained by enzymatic digestion method and characterized by flow cytometry analysis, real-time PCR, bioinformatics analysis, immunohistochemistry, and Western blot. Plasma samples were analyzed by multiplex assay. ResultsThe number of inflammation-associated CD86+ and CX3CR1+ cells was significantly higher in the early-onset preeclampsia while the portion of CD163+ cells was significantly higher among studied groups. We observed significant increase of endothelin-1 gene expression and a significant decrease in eNOS and GNB3 expression and TGFβ relative protein level in decidual cells of the early-onset preeclampsia samples. We also revealed elevation of pro- and anti-inflammatory cytokines in plasma of preeclampsia groups. DiscussionOur findings reflect profound early-onset preeclampsia-associated alterations in the decidua and emphasize the importance of the decidua as a link in the development of preeclampsia.

1378. Reservoirs of Transmission of Resistant Gram-negative Pathogens Responsible for Neonatal Sepsis among Hospitalized Neonates in Pune, India

BackgroundNeonatal infections with resistant Gram-negative (GN) organisms are associated with high rates of mortality, with limited antibiotic treatment options. The role of maternal colonization and environmental GN organisms as reservoirs for transmission to neonates has not been well described.MethodsWe performed a prospective cohort study from October 12, 2018, until October 31, 2019, to describe the role of maternal and environmental GN colonization in BSI among neonates admitted to the neonatal intensive care unit (NICU) at a tertiary care center in Pune, India. Women admitted to Labor & Delivery with risk factors for neonatal sepsis who provided consent were enrolled and their neonates were followed until hospital discharge. For neonates who developed bloodstream infection (BSI), colonization with resistant GN organisms was assessed in their mothers from frozen vaginal and rectal swabs collected at enrollment and at delivery and in the neonates from frozen skin swabs and peri-rectal swabs collected at day of life (DOL) 0, 3, 7, and weekly until discharge. Environmental colonization was assessed with weekly sampling of unit sinks and the immediate neonatal care environment. Colonization samples were processed to identify organisms that matched neonatal blood culture isolates.Results953 women were enrolled, of whom 741 (78%) received antepartum antibiotics. Among 987 live born neonates, 12 (1%) died in the delivery room and 257 (26%) required NICU admission. Among neonates admitted to the NICU, 143 (56%) had at least one blood culture, of which 28 (20%) were positive; 21 (75%) had a GN BSI. The most common cause of neonatal BSI was Klebsiella pneumoniae, and 8 (38%) GN BSI were due to a carbapenem-resistant organism. No organism isolated from maternal samples matched organism and resistance pattern from neonatal blood culture. Matching strains were found in unit sinks and neonatal rectal and skin samples (Figure 1).Organism recovery from swabs and match to bloodstream isolate by sample source and time of collection from birth ConclusionAmong neonates born to mothers with risk factors for neonatal sepsis, GN organisms were the most common cause of neonatal BSI. Environmental and neonatal colonization may represent important reservoirs of transmission for these pathogens among neonates hospitalized in a tertiary care NICU in Pune, India.Disclosures All Authors: No reported disclosures

Synergistic action of estradiol and PGE2 on endometrial transcriptome in vivo resembles pregnancy effects better than estradiol alone†.

Successful pregnancy establishment in mammals depends on numerous interactions between embryos and the maternal organism. Estradiol-17β (E2) is the primary embryonic signal in the pig, and its importance has been questioned recently. However, E2 is not the only molecule of embryonic origin. In pigs, prostaglandin E2 (PGE2) is abundantly synthesized and secreted by conceptuses and endometrium. The present study aimed to determine the role of PGE2 and its simultaneous action with E2 in changes in porcine endometrial transcriptome during pregnancy establishment. The effects of PGE2 and PGE2 acting with E2 were studied using an in vivo model of intrauterine hormone infusions, and were compared to the effects of E2 alone and conceptuses' presence on day 12 of pregnancy. The endometrial transcriptome was profiled using gene expression microarrays followed by statistical analyses. Downstream analyses were performed using bioinformatics tools. Differential expression of selected genes was verified by quantitative polymerase chain reaction. Microarray analysis revealed 2413 differentially expressed genes (DEGs) in the endometrium treated simultaneously with PGE2 and E2 (P<0.01). No significant effect of PGE2 administered alone on endometrial transcriptome was detected. Gene ontology annotations enriched for DEGs were related to multiple processes such as: focal adhesion, vascularization, cell migration and proliferation, glucose metabolism, tissue remodeling, and activation of immune response. Simultaneous administration of E2 and PGE2 induced more changes within endometrial transcriptome characteristic to pregnancy than infusion of E2 alone. The present findings suggest that synergistic action of estradiol-17β and PGE2 resembles the effects of pregnancy on endometrial transcriptome better than E2 alone.

Changes in the distribution of endogenous hormones in Phyllostachys edulis 'Pachyloen' during bamboo shooting.

In this study, we investigated the changes in the distribution and regulation of endogenous hormones in Phyllostachys edulis ‘Pachyloen’ during bamboo shooting. Enzyme-linked immunosorbent assay was used to measure the mass fractions of indole-3-acetic acid (IAA), gibberellic acid (GA), zeatin riboside (ZR), and abscisic acid (ABA) in rhizomes, shoots, and maternal bamboo organs during shoot sprouting, shoot growth, and new-bamboo formation. Measurements were compared among bamboo parts and developmental periods. The overall mass fractions of IAA and ABA were significantly higher than those of ZR and GA, driven by differences among bamboo parts and developmental periods. The abundance of each endogenous hormone varied among bamboo parts and developmental periods. During bamboo shooting, ABA had the highest mass fraction in all bamboo parts sampled, followed by IAA, GA, and ZR. Among bamboo parts, rhizomes had more IAA, ZR, and GA than the other parts, but significantly less ABA. Winter shoots had higher ZR: IAA and GA: IAA ratios than rhizomes and maternal bamboo organs. During shoot growth, ABA was the most abundant hormone in rhizomes and maternal bamboo organs, followed by IAA, ZR, and GA. In contrast, IAA was the most abundant hormone in spring shoots, followed by ABA, ZR, and GA. Maternal bamboo organs had a significantly higher ZR: GA ratio, and significantly lower IAA: ABA, ZR: ABA, and GA: ABA ratios than rhizomes. Spring shoots had significantly higher IAA: ABA, ZR: ABA, and GA: ABA ratios than rhizomes and maternal bamboo organs; significantly higher ZR mass fractions, and ZR: GA and ZR: IAA ratios and significantly lower ABA mass fractions than rhizomes; and significantly higher GA: IAA ratio than maternal bamboo organs. During new-bamboo formation, ABA was the most abundant hormone in rhizomes, winter shoots, and maternal bamboo organs, followed by IAA, ZR, and GA. Maternal bamboo organs had significantly lower IAA mass fractions and significantly higher ABA mass fractions than rhizomes and new bamboo tissue. IAA and ABA abundances exhibited an inverse relationship in rhizomes and maternal bamboo organs. GA: ABA and GA: IAA ratios decreased gradually and other hormone ratios exhibited parabolic trends over the bamboo-shooting period, with the highest ratios observed in new bamboo tissues. Overall, the coordination or antagonism among endogenous hormones plays a key regulatory role in bamboo shoot growth. The formation of thick walls in P. edulis ‘Pachyloen’, one of its major traits, may be partially attributed to the relatively high IAA and ZR and low GA mass fractions.

Orexin B affects the transcriptome of incubated in vitro porcine endometrial explants from the early-implantation period.

This study determined the effect of orexin B (OXB) on the porcine endometrial transcriptome during the embryo attachment phase. Microarray analyses of gene ontology (GO), biological pathways, networks and differentially expressed genes (DEG) were performed. Orexin B influenced the expression of 887 genes (fold change>1.2; p<.05): 620 genes were up-regulated, and 267 were down-regulated. The analysis of the relationship between DEG revealed that OXB interacts with genes linked with processes such as cell hormone binding, regulation of hormone levels, lipid transport, steroid metabolic processes, the apoptotic signalling pathway and the acute inflammatory response, which are pivotal for reproductive success. Orexin B played a bivalent role in the early-pregnant uterus by limiting the pregnancy outcome, promoting embryo development, suppressing the immune system and, consequently, preventing embryo rejection. These findings suggest that OXB could be responsible for the proper course of gestation by adapting litter size to the metabolic status of the maternal organism.

Assessing the safety of using the dry extract of Justicia pectoralis Jacq. (Acanthaceae) during pregnancy of Wistar rats

Ethnopharmacological relevanceJusticia pectoralis Jacq. (Acanthaceae), popularly known as tilo, chambá and anador, is widely used in folk medicine in Latin American countries as a sedative, anti-anxiety, reducing menopause symptoms and in the treatment of pathologies of the respiratory tract. Although J. pectoralis is widely used by the female population, there are no studies on the safety of using this species during pregnancy. Aim of this studyTo evaluate the effects of prenatal treatment with dry extract from the aerial parts of J. pectoralis on maternal and developmental toxicity in Wistar rats. Material and methodsPregnant Wistar rats (n = 10/group) were treated from gestational day (GD) 0–20 with the vehicle (control group) or with the dry extract of J. pectoralis at doses of 300, 600 or 1200 mg/kg. During pregnancy, clinical signs of toxicity, maternal weight, feed and water intake were evaluated. On GD 21, rats were anesthetized and intracardiac blood was collected to evaluate biochemical parameters. During cesarean section, reproductive performance parameters were recorded. The liver, kidneys, uterus and ovaries were removed for histopathological analysis. Fetuses were examined for possible malformations and/or skeletal and visceral variations. ResultsTreatment with dry extract of J. pectoralis did not alter weight gain, feed intake or biochemical and maternal reproductive performance parameters There were also no significant histopathological changes in the maternal organs, as well as external, skeletal and visceral malformations in the fetuses. ConclusionOral administration of J. pectoralis dry extract during pregnancy did not induce maternal toxicity or embryotoxic and teratogenic effects.

Transgenerational effects of methyl farnesoate on Daphnia pulex clones: Male and ephippia production and expression of genes involved in sex determination

Abstract Environmental sex determination implies that sex is defined by environmental factors influencing the maternal organism and/or oocytes. It provides population sex ratios that will maximise the sustainability of the population under incipient environmental conditions. Environmental factors responsible for sex determination include temperature, photoperiod, food availability, and population density. These cues stimulate the release of chemical signalling molecules (i.e. hormones) that determine the sex of newborns. We have analysed the responses of three Daphnia pulex clones (I, K, and S), isolated from different natural populations, to juvenile hormone methyl farnesoate (MF) in terms of survivorship, fecundity, production of males and ephippia, and expression of genes involved in sex determination (dsx1) and hormonal regulation (JHAMT, Met, RXR). Clonal individuals were exposed to: (1) high MF concentration (0.8 µM) combined with stressful conditions; (2) low MF concentration (0.15 µM) combined with optimal conditions of population density and food availability in two subsequent generations. The genetically different clones of D. pulex differed in the propensity for male and ephippia production and in the sensitivity to the stimuli that lead to the switch from parthenogenetic to sexual reproduction. A significant induction of male production was observed in all three clones when exposed to MF. In conditions mimicking crowding, only clone S produced male offspring even in absence of MF and showed higher expression levels of JHAMT and dsx1 genes. This response suggests that clone S has a high propensity to produce males probably due to a high sensitivity of receptors to environmental stimuli activating the endogenous biosynthesis of MF. However, clone S exposed to high MF concentration produced fewer males than clones I and K, which generally have a low natural propensity to produce males. High MF concentration coupled with conditions mimicking crowding, probably activated a feedback mechanism in clone S via the differential modulation of genes involved in the synthesis as well in the degradation of MF. Exposure to low MF concentration for two subsequent generations resulted in a reduction of male progeny production from the first (G1) to the second (G2) generation. All analysed genes were up‐regulated in both generations treated with MF, but with lower expression in G2. The reduced up‐regulation of the dsx1 gene matched with the lower male production. Based on our results and literature data, we hypothesised that the maternal dsx1 mRNA probably plays some role early in oocyte development, and causes the eggs that receive the dsx1 signal to develop into males. Exposure to MF for two generations significantly increased ephippia production. These results suggest that the induction of male and ephippia might have a common root in the MF pathway. The effect of MF on life‐history traits (delay in the age at maturity and fecundity reduction), sex ratio, and ephippia production suggests a direct impact of the juvenile hormone on the level of population growth. Thus, as a consequence of the switch from parthenogenetic to sexual reproduction, MF influences Daphnia population metrics and in this way probably maximises the sustainability of the population under variable environmental conditions.

Effect of Prenatal Hypoxia on Activity of the Soluble Forms of Cholinesterases in Rat Brain Structures during Early Postnatal Ontogenesis

The dynamics of soluble AChE and BChE (EC 3.1.1.7; EC 3.1.1.8) in the hippocampus, cortex, cerebellum and blood serum of control rats and rats exposed to prenatal hypoxia was studied on days 5, 10 and 30 of postnatal development. The activity of soluble AChE in all brain structures was found to reach its maximum on postnatal day 10, and then either persisted at this level (in the cerebellum and cortex) or decreased by day 30 (in the hippocampus). Similar changes were found in the activity of BChE, which was roughly one level of magnitude lower than of AChE in all the brain structures studied in this work. Prenatal hypoxic exposure on day 14 of embryonic development led to statistically significant changes in the activity of soluble AChE and BChE in all the brain structures studied, as well as in blood serum. In rats exposed to prenatal hypoxia, serum AChE and BChE activities on postnatal days 5 and 10 were significantly lower while, on day 30, they were indistinguishable from the control values. Thus, oxygen deficit in the maternal organism during pregnancy significantly affects the activity of soluble forms of the key enzymes of the central and peripheral cholinergic systems, indicating possible changes in the formation of these systems in early ontogenesis. This may lead both to impaired neurogenesis and malformation of the motor and cognitive functions and general homeostatic imbalance during animal and human development.

Morphofunctional pecularrities and sialoglicans in lungs from offspring born from female rats with thyroid gland hyperfunction

Background. Over the last decade, there has been a global pending to increase the incidence of chronic obstructive pulmonary disease by 25% in men and 69% in women. Objective. To study the role of sialoglycans according to wheat germ lectin receptors (WGA) and morphofunctional features of offspring rats, which developed in conditions of hyperfunction of the thyroid gland of the maternal organism. Methods. The experimental study was performed on the offsprings of 20 females (10 control, 10 experimental) rats of the Wistar line. For 20 days before coupling the females of the experimental group received the drug L-thyroxine (Berlin-Chemie) at a dose of 150 μg / kg body weight. After euthanasia by overdose of ether anesthesia, the offspring from control and experimental females were taken lungs on the 1st, 10th, 20th and 40th day of postnatal development. Histological material was fixed in 4% neutral formalin, compacted and poured into paraffin blocks, made sections 5-7 μm thick. Review preparations were stained with hematoxylin and eosin according to standard methods. Wheat germ lectin WGA (Triticum vulgare) labeled with peroxidase-specific DGlcNAc NeuNAc was used to detect sialoglycans. Results. On the 1-40th day of postnatal development, the lungs of rats of the intact group show up typical morphology characteristic of rat lungs. On the tenth day of postnatal development in the offsprings lungs from females receiving L-thyroxine visually increases the number of alveoli, indicating an intensification of morphogenesis of lung tissue. Lectinohistochemical studies showed that on the first day of postnatal development in the lungs of rats of the intact group, receptors for sialospecific lectin WGA were identified on the surface of ciliated cells of the bronchial tree and vascular endothelium, while in the experimental group receptors for this lectin were found significantly in alveolar macrophages, visualised more often than in the lungs of the offspring from rats of the control group. Whereas on the 20th-40th day of postnatal development the number of macrophages with the presence of sialoglycans decreased. Conclusion. Studies have shown that in the lungs of offsprings from females receiving L-thyroxine, there are processes of intensification of the structural components of the lungs and the appearance of alveolar macrophages with the presence of sialospecific lectin WGA receptors, the number of which decreases during postnatal ontogenesi, that indicating a decrease of the immunity.

Acute kidney injury during pregnancy leads to increased sFlt-1 and sEng and decreased renal T regulatory cells in pregnant rats with HELLP syndrome

BackgroundThe incidence of acute kidney injury (AKI) during pregnancy precedes a high maternal mortality rate of 20–40%. AKI during pregnancy has multiple etiologies; however, the more common are maternal hypertensive disorders, which include preeclampsia and HELLP (hemolysis, elevated liver enzyme, low platelet) syndrome. Therefore, we sought to assess the impact of AKI on blood pressure, kidney injury, and anti-angiogenic factors during pregnancies with and without HELLP syndrome.MethodsOn gestational day (GD) 12, mini-osmotic pumps were inserted into a subset of normal pregnant (NP) rats infusing 4.7 μg/kg soluble fms-like tyrosine kinase-1 (sFlt-1) and 7 μg/kg soluble endoglin (sEng) to induce HELLP syndrome. On GD18, the renal pedicles were occluded for 45 min to induce AKI via bilateral ischemia reperfusion in a subset of NP (n = 18) or HELLP (n = 20) rats. Control NP (n = 20) and HELLP (n = 20) rats underwent a SHAM surgery on GD18. Plasma, urine, and maternal organs were saved for further analysis. Renal injury was assessed via renal histopathology, glomerular filtration rate (GFR), T cell infiltration, and assessment of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL). Data was measured via two-way analysis of variance with Tukey’s test for post hoc analysis.ResultsBlood pressures were increased in HELLP+AKI rats (p = 0.0001); both NP+AKI and HELLP+AKI rats had increased lactate dehydrogenase (p < 0.0001) and aspartate aminotransferase levels (p < 0.0001), and decreased platelet levels (p < 0.001) vs. NP rats. HELLP+AKI (p = 0.002) and HELLP rats (p = 0.0002) had evidence of renal fibrosis vs. NP rats. GFR was decreased in HELLP+AKI (p = 0.01) rats vs. NP rats. Urinary KIM-1 was increased in NP+AKI rats vs. NP (p = 0.003) and HELLP rats (p = 0.01). HELLP+AKI rats had increased urinary KIM-1 vs. NP (p = 0.0008) and HELLP rats (p = 0.004) and increased NGAL vs. HELLP rats (p = 0.002). HELLP+AKI rats had increased sFlt-1 (p = 0.009) vs. NP rats. NP+AKI (p = 0.02) and HELLP+AKI (p = 0.007) rats had increased sEng vs. NP rats. CD3+CD4+ T cells were significantly increased in HELLP+AKI rats vs. NP (p = 0.0002) and NP+AKI (p = 0.05) rats. T regulatory cells were significantly decreased in HELLP+AKI (p = 0.03) and NP+AKI (p = 0.02) rats vs. NP rats; there were no changes between groups in T helper 17 cells (p = 0.34).ConclusionThe findings in this study suggest that AKI during pregnancy contributes to increased blood pressure and biochemical markers for HELLP syndrome, creates an anti-angiogenic imbalance, and exacerbates kidney injury as shown on histopathology, GFR, and kidney injury markers.

Placental extracellular vesicles and pre-eclampsia.

Pre-eclampsia is a hypertensive disease of pregnancy characterized by new-onset hypertension, with either proteinuria and/or organ dysfunction. Pre-eclampsia is a leading cause of maternal morbidity and mortality; however, the underlying cellular and molecular mechanisms are not well understood. There is consensus that the underlying mechanism(s) resulting in pre-eclampsia is centered around abnormal placentation, inadequate spiral-artery remodeling, and deficiency in trophoblast invasion, resulting in impaired maternal blood flow to the placenta and a release of signals and/or inflammatory mediators into maternal circulation triggering the systemic manifestations of pre-eclampsia. ER stress, resulting in impaired autophagy and placental release of aggregated proteins, may also confer systemic stress to maternal organs in pre-eclampsia. Extracellular vesicles (EVs), lipid-bilayer enclosed structures containing macromolecules including proteins, miRNA, and other important nucleotides, have been suggested to play an important role in this maternal-fetal communication. Circulating EVs are present in greater quantity in the plasma of pre-eclampsia subjects compared to normal pregnancy, and the placental derived EVs have been shown to have altered protein and RNA cargo. In this review, we will focus on EVs and their role in pre-eclampsia, specifically their role in immune responses, inflammation, altered angiogenesis, and endothelial dysfunction.

Bovine peripheral blood MSCs chemotax towards inflammation and embryo implantation stimuli.

Mesenchymal stem cells (MSCs) have a great potential in regenerative medicine because of their multipotential and immunoregulatory capacities, while in early pregnancy they could participate in the immunotolerance of the mother towards the embryo. Peripheral blood constitutes an accessible source of MSCs. We successfully isolated peripheral blood MSC (pbMSCs) lines, with or without previous bone marrow mobilization. All pbMSCs lines obtained in both conditions presented classical MSC markers and properties, alkaline phosphatase activity and multipotent capacity to differentiate among adipogenic, osteogenic or chondrogenic lineages, and suppressed the proliferation of T cells. pbMSCs showed migratory capacity without cytokine stimulation while increasing their migration rate in the presence of inflammatory or embryo implantation stimuli. Interestingly, in contrast to MSCs derived from endometrial tissue, three pbMSCs lines also showed increased migration towards the IFN-τ implantation cytokine. Moreover, the secretome produced by an early implantation stage embryonic trophectoderm cell line showed a chemoattractant effect in pbMSCs. Our results suggest that circulating MSCs are present in the peripheral blood under healthy conditions. The fact that both the inflammation and implantation signals induced pbMSCs chemotaxis highlights MSC heterogeneity and suggests that their migratory capacity may differ according to their tissue of origin and would suggest the possible active recruitment of MSCs from bone marrow during pregnancy to repress the immune response to prevent the embryo rejection by the maternal organism.