Preterm Rats Research Articles

Ultrastructural Features of Left Ventricle Cardiomyocytes in Preterm Newborn Rats.

The structure of left ventricular cardiomyocytes of 1 day preterm newborn rats was studied using transmission electron microscopy. It was shown that the relative area of the nucleus in cardiomyocytes of preterm rats is lower, and the relative area of the cytoplasm is higher than in full-term rats, while the relative areas of myofibrils and mitochondria do not differ. In cardiomyocytes of preterm rats damaged mitochondria, subsegmental myofibrillar contracture, and cytoplasmic swelling were found on the first postnatal day. Preterm birth in rats, in contrast to birth at term, is accompanied by the development of a number of ultrastructural damages in cardiomyocytes.

Prophylactic and Therapeutic Effects of Progesterone on the Preterm Brain Injury Rat Model.

Neurodevelopmental disorders are chronic conditions affecting behavior, cognition, and social function, often arising from early brain development disruptions. Preterm infants are particularly vulnerable to brain injuries, such as periventricular leukomalacia, which can lead to long-term disabilities. This study aimed to investigate the neuroprotective effect of progesterone in reducing the severity of a preterm brain injury in rat model. A preterm brain injury rat model was established using lipopolysaccharide to induce brain injury. The neuroprotective effects of progesterone were evaluated through histological assessments comparing treated and untreated groups. The study also aimed to assess the efficacy of progesterone in controlling brain injury severity. The findings suggest that progesterone exhibits neuroprotective properties, with a significant difference in the severity of brain injury. The histological evaluations suggest that progesterone may reduce inflammation and promote neuronal survival in preterm brain injury. The administration of progesterone shows promising results as a therapeutic strategy for preventing and treating brain injuries in preterm rat pups. Further research is needed to explore the underlying mechanisms and potential clinical applications of the hormone.

Role and mechanism of epithelial-mesenchymal transition in a rat model of bronchopulmonary dysplasia induced by hyperoxia exposure

To investigate the role and mechanism of epithelial-mesenchymal transition (EMT) in a rat model of bronchopulmonary dysplasia (BPD). The experiment consisted of two parts. (1) Forty-eight preterm rats were randomly divided into a normoxia group and a hyperoxia group, with 24 rats in each group. The hyperoxia group was exposed to 85% oxygen to establish a BPD model, while the normoxia group was kept in room air at normal pressure. Lung tissue samples were collected on days 1, 4, 7, and 14 of the experiment. (2) Rat type II alveolar epithelial cells (RLE-6TN) were randomly divided into a normoxia group (cultured in air) and a hyperoxia group (cultured in 95% oxygen), and cell samples were collected 12, 24, and 48 hours after hyperoxia exposure. Hematoxylin-eosin staining was used to observe alveolarization in preterm rat lungs, and immunofluorescence was used to detect the co-localization of surfactant protein C (SPC) and α-smooth muscle actin (α-SMA) in preterm rat lung tissue and RLE-6TN cells. Quantitative real-time polymerase chain reaction and protein immunoblotting were used to detect the expression levels of EMT-related mRNA and proteins in preterm rat lung tissue and RLE-6TN cells. (1) Compared with the normoxia group, the hyperoxia group showed blocked alveolarization and simplified alveolar structure after 7 days of hyperoxia exposure. Co-localization of SPC and α-SMA was observed in lung tissue, with decreased SPC expression and increased α-SMA expression in the hyperoxia group at 7 and 14 days of hyperoxia exposure compared to the normoxia group. In the hyperoxia group, the mRNA and protein levels of TGF-β1, α-SMA, and N-cadherin were increased, while the mRNA and protein levels of SPC and E-cadherin were decreased at 7 and 14 days of hyperoxia exposure compared to the normoxia group (P<0.05). (2) SPC and α-SMA was observed in RLE-6TN cells, with decreased SPC expression and increased α-SMA expression in the hyperoxia group at 24 and 48 hours of hyperoxia exposure compared to the normoxia group. Compared to the normoxia group, the mRNA and protein levels of SPC and E-cadherin in the hyperoxia group were decreased, while the mRNA and protein levels of TGF-β1, α-SMA, and E-cadherin in the hyperoxia group increased at 48 hours of hyperoxia exposure (P<0.05). EMT disrupts the tight connections between alveolar epithelial cells in a preterm rat model of BPD, leading to simplified alveolar structure and abnormal development, and is involved in the development of BPD. Citation:Chinese Journal of Contemporary Pediatrics, 2024, 26(7): 765-773.

Plant-Derived Substances for Prevention of Necrotising Enterocolitis: A Systematic Review of Animal Studies.

Inflammation, oxidative injury, and gut dysbiosis play an important role in the pathogenesis of necrotising enterocolitis (NEC). Plant-derived substances have historically been used as therapeutic agents due to their anti-inflammatory, antioxidant, and antimicrobial properties. We aimed to review pre-clinical evidence for plant-derived substances in the prevention and treatment of NEC. A systematic review was conducted using the following databases: PubMed, EMBASE, EMCARE, MEDLINE and Cochrane Library (PROSPERO CRD42022365477). Randomized controlled trials (RCTs) and quasi-RCTs that evaluated a plant-derived substance as an intervention for NEC in an animal model of the illness and compared pre-stated outcomes (e.g., clinical severity, severity of intestinal injury, mortality, laboratory markers of inflammation and oxidative injury) were included. Sixteen studies (n = 610) were included in the systematic review. Ten of the sixteen included RCTs (Preterm rat pups: 15, Mice: 1) reported mortality and all reported NEC-related histology. Meta-analysis showed decreased mortality [12/134 vs. 27/135; RR: 0.48 (95% CI: 0.26 to 0.87); p = 0.02, 10 RCTs] and decreased NEC in the experimental group [24/126 vs. 55/79; RR: 0.34 (95% CI: 0.22 to 0.52); p < 0.001, 6 RCTs]. Markers of inflammation (n = 11) and oxidative stress (n = 13) improved in all the studies that have reported this outcome. There was no significant publication bias for the outcome of mortality. Plant-derived substances have the potential to reduce the incidence and severity of histologically diagnosed NEC and mortality in rodent models. These findings are helpful in guiding further pre-clinical studies towards developing a food supplement for the prevention of NEC in preterm infants.

A Preterm Rat Model for Pain Studies.

This research delves into the consequences of consistent pinprick stimulation on preterm offspring to ascertain its long-term implications for pain sensitivity. The primary objective of this protocol was to investigate the impact of neonatal pinprick stimuli on the pain threshold in the later stages of life using a preterm rat model. By establishing this model, we aim to advance the research on understanding and managing early postnatal pain associated with prematurity. The findings of this study indicate that while the baseline thresholds to mechanical stimuli remained unaffected, there was a notable increase in mechanical hypersensitivity following complete Freund's adjuvant (CFA) injection in adult rats. Interestingly, compared with male rats, female rats demonstrated heightened inflammatory hypersensitivity. Notably, maternal behavior, the weight of the litters, and the growth trajectory of the offspring remained unchanged by the stimulation. The manifestation of altered nociceptive responses in adulthood after neonatal painful stimuli could be indicative of changes in sensory processing and the functioning of glucocorticoid receptors. However, further research is needed to understand the underlying mechanisms involved and to develop interventions for the consequences of prematurity and neonatal pain in adults.

Соотношение удельного объема коллагена I и III типа в миокарде левого желудочка преждевременно родившихся крыс

Introduction. Type I/III collagen ratio in the myocardium plays a key role in determining the biomechanical properties of the heart. The aim was to study type I/III collagen ratio of the myocardial stroma of the left ventricle in prematurely born rats. Materials and methods. The experiment included 120 Wistar rats of both sexes, which were divided into three groups. The control group included full-term animals (22 days of gestation), and groups 1 and 2 involved preterm animals (21.5 and 21 days of gestation, respectively). We used histological (Masson staining) and immunohistochemical (detection of type I and III collagens) methods to analyze the left ventricular myocardium in term and preterm rats on months 1, 1.5, 2, and 6 of the postnatal period. Results. Preterm birth leads to the development of myocardial fibrosis, whose severity correlates with the degree of prematurity. Due to preterm birth, the accumulation rate of type I collagen in the left ventricular myocardium accelerates. From month 2 of the postnatal period, the specific volume of type I collagen in term and preterm rats does not differ. An increase in the specific volume of type III collagen in the left ventricular myocardium in preterm rats is observed up to month 6 of the postnatal period. Preterm birth of rats results in decreased type I/III collagen ratio in the left ventricular myocardium in months 2 and 6 of the postnatal period. Conclusion. Preterm birth of rats leads to adaptive remodeling of the connective tissue of the left ventricular myocardium, which consists in the initial (1–1.5 months of the postnatal period) growth in the specific vol-ume of type I collagen and further (up to month 6 of the postnatal period) increase in the specific volume of type III collagen, compared to the same parameters of the myocardium of full-term animals. The decrease in type I/III collagen ratio on months 2 and 6 of the postnatal period indicates a change in biomechanical properties of the left ventricular myocardium in prematurely born rats. Keywords: preterm birth, prematurity, cardiac remodeling, myocardial fibrosis, type I collagen, type III collagen

Alpha-lipoic acid protects against hyperlipidemia-induced testicular damage in premature rats

This study was designed to investigate the effect of hypercholesterolemia on the reproductive performance of premature male rats and to evaluate the influence of alpha lipoic acid (ALA) in conserving their fecundity. Sixty rats were randomly assigned to one of three groups. The control group (CG n=20 rats), cholesterol feeding group 1 (CFG1 n=20 rats) were fed 1.5% cholesterol with diet for one month, and cholesterol feeding group 2 (CFG2 n= 20 rats) were fed 1.5% cholesterol with diet + ALA 100 mg/kg body weight supplied by water for one month. The results revealed that compared to CG and CFG2, CFG1's body weight increased significantly. After consuming cholesterol for one month, CFG1's lipid profile revealed a substantial rise in blood cholesterol and triglycerides when compared to CG and the group that consumed ALA CFG2. In comparison to CGF1 and CG, the results of the sperm parameters in CGF2 demonstrated a large rise in sperm count with sperm live percentage and a considerable decrease in sperm abnormality %. Rats from CFG1 had significantly lower serum testosterone levels than rats from CFG2 and CG, according to the hormonal profile. We conclude that the significance of alpha lipoic acid (ALA) in preserving fertility ALA is a strong antioxidant that may preserve the parameters of the sperm of hyperlipidemic preterm rats, which may improve the capacity of hyperlipidemic rats to conceive.

SIRT1 alleviates insulin resistance and respiratory distress in late preterm rats by activating QKI5-mediated PPARγ/PI3K/AKT pathway

ABSTRACT Neonatal respiratory distress syndrome (NRDS) is a common complication of gestational diabetes mellitus (GDM) and late preterm births. Research suggests that SIRT1 was involved in LPS-induced acute respiratory distress syndrome, but its mechanism remains to be further explored. Here, pregnant rats were intraperitoneally injected with 45 mg/Kg streptozotocin at day 0 of gestation to induce GDM and injected with LPS at day 17 of gestation to induce late preterm birth. Pioglitazone (a PPARγ agonist) was administered from day 17 to parturition in GDM group, and it was administered for 3 days before LPS injection in late preterm birth group. SRT1720 (a SIRT1 activator) was administered by oral gavage from day 0 to day 17 in both groups. Our data showed that activation of SIRT1 or PPARγ alleviated the abnormal blood glucose metabolism and lung tissue injury, downregulated expression of surfactant proteins (SP-B and SP-C), and decreased activation of the PI3K/AKT pathway induced by GDM and late preterm birth in neonatal rats. Moreover, an insulin resistance model was established by treating primary AT-II cells with insulin. Activation of SIRT1 reversed insulin-induced reduction in cell proliferation, glucose consumption, SP-B and SP-C expression, and the activity of the PI3K/AKT pathway and increase in cellular inflammation and apoptosis. Mechanistically, SIRT1 upregulated PPARγ expression via deacetylation of QKI5, an RNA binding protein that can stabilize its target mRNA molecules, and then activated the PI3K/AKT pathway. In conclusion, SIRT1 promotes the expression of PPARγ via upregulation of QKI5 and activates the PI3K/AKT pathway, thus mitigating NRDS caused by GDM and late preterm birth.

Structural Features of Ascending Aorta Wall in Premature Born Rats

Preterm birth has a pronounced effect on all body systems, including the cardiovascular system, which undergoes significant adaptive changes in the early postnatal period of ontogenesis. A comprehensive understanding of the consequences of preterm birth is essential to ensure early prevention, detection and treatment of long-term adverse health effects. The aim of our study was to evaluate the effect of preterm birth on the structure of the wall of the ascending aorta in preterm rats. The paper presents the results of histological and morphometric analysis of ascending aorta wall in Wistar rats born on the 21st and 21.5 days of pregnancy (the total gestation period is 22 days). In ascending aorta wall of preterm born rats, signs of elastolysis and a violation of the parallelism of the elastic fenestrated membranes are found. It has been shown that preterm birth leads to a decrease in the specific volume of elastic fibers and an increase in collagen fibers in the meddle shell of ascending aorta wall in prematurely born rats.

Wnt5a-Flt1 activation contributes to preterm altered cerebral angiogenesis after prenatal inflammation.

Intraventricular hemorrhage (IVH) causes morbidity and mortality in preterm infants and prenatal exposure to inflammation contributes to brain injury. Moreover, prenatal exposure to severe inflammation increases the risk of IVH in preterm neonates. The current study investigated whether intrauterine exposure to inflammation affects cerebral angiogenesis and its underlying mechanisms. Wnt5a, flt1, and vascular endothelial growth factor (VEGF)-A levels in cord blood serum (stored in a bio-bank) of the enrolled patients were measured via enzyme-linked immunosorbent assay. A preterm prenatal inflammation exposure model was established in rats by intraperitoneal injection intraperitoneally during pregnancy. Angiogenesis of cerebral tissue was analyzed using immunohistochemistry. Wnt5a, flt1, and VEGF-A expression levels were measured via immunohistochemistry, immunofluorescence, or western blotting. The correlation between Wnt5a and flt1 expression and the cerebral vessel area was also analyzed. The Wnt5a and flt1 levels in the cord blood serum were significantly higher in the amnionitis group than in the non-amnionitis group. The VEGF-A level in the cord blood serum was significantly lower in the amnionitis group. In the rat model, preterm rats in the prenatal inflammation group exhibited increased microglial cell infiltration and decreased vessel area and diameter in the cerebral tissue compared to the control group. Wnt5a was located in microglial cells, and Wnt5a and flt1 expression in brain tissue significantly increased after prenatal lipopolysaccharide (LPS) exposure. VEGF-A expression declined after prenatal LPS exposure. The cerebral vessel area was negatively correlated with Wnt5a and flt1 expression. Disordered cerebral angiogenesis is associated with increased Wnt5a-Flt1 activation in microglial cells after exposure to intrauterine inflammation.

Immunohistochemical Study of Matrix Metalloproteinases 2 and 9 in the Left Ventricle of Preterm Rats Heart in the Late Postnatal Development

Immunohistochemical detection of matrix metalloproteinases (MMP) 2 and 9 was carried out in the myocardium of the left ventricle of prematurely born (21 and 21.5 days of gestation) and full-term (22 days of gestation) rats at 42, 56 and 180 days of the postnatal period of ontogenesis. The intensity of immunopositive staining was assessed by a scoring system. Preterm birth leads to an increase in the intensity of the immunopositive reaction to MMP-2 and MMP-9 in the wall of the left ventricle of rats. An increase in the intensity of the MMP-2 positive reaction in the left ventricle of rats is observed the earlier, the greater the degree of prematurity. The intensity of the MMP-9 positive reaction in the left ventricle of male rats is greater with a more pronounced degree of prematurity. An increase in the intensity of the MMP-2 and MMP-9 positive reaction in the wall of the left ventricle of female rats due to preterm birth is determined exclusively in animals born on the 21st day of pregnancy, that is, with a greater degree of prematurity.

Effects of repetitive pinprick stimulation on preterm offspring: Alterations in nociceptive responses and inflammatory hypersensitivity in adulthood

IntroductionThis study investigates the effects of repetitive pinprick stimulation on preterm offspring and its impact on nociceptive responses and inflammatory hypersensitivity in adulthood. ObjectivesThe objective is to shed light on the potential long-term consequences of neonatal pain and prematurity on sensory processing. MethodsTerm and preterm rats were subjected to repetitive pinprick (PP) stimulation or control (CC) during the neonatal period. Adult rats received CFA injection to induce inflammatory hypersensitivity, and mechanical hypersensitivity was measured. Gender differences in inflammatory hypersensitivity were also examined. Maternal behavior, litter weight, and offspring growth were monitored to assess any potential influences of the stimulation on these parameters. ResultsIn preterm rats, the PP stimulation did not affect baseline thresholds to mechanical stimuli, but increased mechanical hypersensitivity after CFA injection in adult rats. Females exhibited greater inflammatory hypersensitivity compared to males. Maternal behavior, litter weight, and offspring growth were not influenced by the stimulation. PP stimulation during the neonatal period led to changes in nociceptive responses in adulthood, potentially altering sensory processing. ConclusionPP stimulation in preterm rats during the neonatal period resulted in changes in nociceptive responses in adulthood, leading to increased inflammatory hypersensitivity. The study emphasizes how early development can significantly impact sensory processing and further highlights the potential long-term consequences of prematurity and neonatal pain on this processing.

Interleukin-6 and interleukin-10 levels in the placenta of preterm rats and their effects on broncholung development.

Interleukin-6 and interleukin-10 levels in the placenta of preterm rats and their effects on broncholung development.

Neonatal hyperbilirubinemia differentially alters the neurochemical profiles of the developing cerebellum and hippocampus in a preterm Gunn rat model.

Neonatal hyperbilirubinemia (NHB) can lead to brain injury in newborn infants by affecting specific regions including the cerebellum and hippocampus. Extremely preterm infants (EPT) are more vulnerable to bilirubin neurotoxicity, but the mechanism and extent of injury is not well understood. A preterm version of Gunn rat model was utilized to investigate severe preterm NHB. Homozygous/jaundiced Gunn rat pups were injected (i.p.) on postnatal day (P) 5 with sulfadimethoxine, which increases serum free bilirubin capable of crossing blood brain barrier and causing brain injury. The neurochemical profiles of the cerebellum and hippocampus were determined using in vivo 1 H MRS at 9.4T on P30 and compared with heterozygous/non-jaundiced control rats. Transcript expression of related genes were determined by real-time quantitative PCR. MRI revealed significant morphological changes in the cerebellum of jaundiced rats. The concentrations of myo-inositol (+54%), glucose (+51%), N-acetylaspartylglutamate (+21%), and the sum of glycerophosphocholine and phosphocholine (+17%) were significantly higher in cerebellum of the jaundiced group compared with control group. Despite the lack of morphologic changes in the hippocampus, the concentration of myo-inositol (+9%) was higher and the concentration of creatine (-8%) and of total creatine (-3%) were lower in the jaundiced group. In the hippocampus, expression of calcium/calmodulin dependent protein kinase II alpha (Camk2a), glucose transporter (Glut) 1, and Glut3 transcripts were downregulated in the jaundiced group. In the cerebellum, the expression of glial fibrillary acidic protein (Gfap), myelin basic protein (Mbp), and Glut1 transcript expression was upregulated in the jaundiced group. These results indicate osmotic imbalance, gliosis, changes in energy utilization and myelination and demonstrate that preterm NHB critically affects brain development in a region-specific manner, with the cerebellum more severely impacted than the hippocampus.

Preterm birth leads to a decreased number of differentiated podocytes and accelerated podocyte differentiation.

Preterm birth was previously identified as a high-risk factor for the long-term development of chronic kidney disease. However, the detailed pattern of podocyte (PD) changes caused by preterm birth and the potential mechanism underlying this process have not been well clarified. In present study, a rat model of preterm birth was established by delivery of pups 2days early and podometric methods were applied to identify the changes in PDs number caused by preterm birth. In addition, single-cell RNA sequencing (scRNA-seq) and subsequent bioinformatic analysis were performed in the preterm rat kidney to explore the possible mechanism caused by preterm birth. As results, when the kidney completely finished nephrogenesis at the age of 3weeks, a reduction in the total number of differentiated PDs in kidney sections was detected. In addition, 20 distinct clusters and 12 different cell types were identified after scRNA-seq in preterm rats (postnatal day 2) and full-term rats (postnatal day 0). The numbers of PDs and most types of inherent kidney cells were decreased in the preterm birth model. In addition, 177 genes were upregulated while 82 genes were downregulated in the PDs of full-term rats compared with those of preterm rats. Further functional GO analysis revealed that ribosome-related genes were enriched in PDs from full-term rats, and kidney development-related genes were enriched in PDs from preterm rats. Moreover, known PD-specific and PD precursor genes were highly expressed in PDs from preterm rats, and pseudotemporal analysis showed that PDs were present earlier in preterm rats than in full-term rats. In conclusion, the present study showed that preterm birth could cause a reduction in the number of differentiated PDs and accelerate the differentiation of PDs.

Protective effect of breviscapine against brain injury induced by intrauterine inflammation in preterm rats and its mechanism

To study the protective effect of breviscapine against brain injury induced by intrauterine inflammation in preterm rats and its mechanism. A preterm rat model of brain injury caused by intrauterine inflammation was prepared by intraperitoneal injections of lipopolysaccharide in pregnant rats. The pregnant rats and preterm rats were respectively randomly divided into 5 groups: control, model, low-dose breviscapine (45 mg/kg), high-dose breviscapine (90 mg/kg), and high-dose breviscapine (90 mg/kg)+ML385 [a nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor, 30 mg/kg] (n=10 each). The number and body weight of the live offspring rats were measured for each group. Hematoxylin-eosin staining was used to observe the pathological morphology of the uterus and placenta of pregnant rats and the pathological morphology of the brain tissue of offspring rats. Immunofluorescent staining was used to measure the co-expression of ionized calcium binding adaptor molecule-1 (IBA-1) and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) in the cerebral cortex of offspring rats. ELISA was used to measure the levels of interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-1β (IL-1β) in the brain tissue of offspring rats. Western blotting was used to measure the expression of Nrf2 pathway-related proteins in the brain tissue of offspring rats. Pathological injury was found in the uterus, and placenta tissue of the pregnant rats and the brain tissue of the offspring rats, and severe microglia pyroptosis occurred in the cerebral cortex of the offspring rats in the model group. Compared with the control group, the model group had significant reductions in the number and body weight of the live offspring rats and the protein expression levels of Nrf2 and heme oxygenase-1 (HO-1) in the brain tissue of the offspring rats (P<0.05), but significant increases in the relative fluorescence intensity of the co-expression of IBA-1 and NLRP3, the levels of the inflammatory factors IL-6, IL-8, and IL-1β, and the protein expression levels of NLRP3 and caspase-1 in the brain tissue of the offspring rats (P<0.05). Compared with the model group, the breviscapine administration groups showed alleviated pathological injury of the uterus and placenta tissue of the pregnant rats and the brain tissue of the offspring rats, significant increases in the number and body weight of the live offspring rats and the protein expression levels of Nrf2 and HO-1 in the brain tissue of the offspring rats (P<0.05), and significant reductions in the relative fluorescence intensity of the co-expression of IBA-1 and NLRP3, the levels of the inflammatory factors IL-6, IL-8, and IL-1β, and the protein expression levels of NLRP3 and caspase-1 in the brain tissue of the offspring rats (P<0.05). The high-dose breviscapine group had a significantly better effect than the low-dose breviscapine (P<0.05). ML385 significantly inhibited the intervention effect of high-dose breviscapine (P<0.05). Breviscapine can inhibit inflammatory response in brain tissue of preterm rats caused by intrauterine inflammation by activating the Nrf2 pathway, and it can also inhibit microglial pyroptosis and alleviate brain injury.

Effect of preterm birth in rats on proliferation and hyperplasia of cardiomyocytes

Aim. To identify the effect of preterm birth on proliferation and hyperplasia of cardiomyocytes in the early postnatal period of ontogenesis in rats.Materials and methods. Preterm birth (on day 21 and 21.5 of gestation) in Wistar rats was induced by subcutaneous administration of mifepristone. Immunohistochemistry was used to identify and calculate the number of Ki67-positive and Mklp2-positive cardiomyocytes in the left ventricle of preterm and full-term rats on days 1, 2, 3, 4, 5, and 6 of postnatal ontogenesis. Statistical analysis of morphometric parameters was performed using the Shapiro – Wilk test and Mann – Whitney test with the Bonferroni correction.Results. We revealed an increase in the number of Ki67-positive cardiomyocytes in the left ventricle of the rats: on day 1 of postnatal ontogenesis (in the rats born on day 21 of gestation) and on days 3–5 of postnatal ontogenesis (in the rats born on day 21.5 of gestation). Preterm birth in rats did not result in a change in the number of Mklp2-positive cardiomyocytes in the left ventricular wall.Conclusion. A change in the pattern of Ki67 expression by cardiomyocytes in the rats born 12 or 24 hours before full term was demonstrated in the early postnatal period of ontogenesis. An isolated increase in Ki67 expression without a change in Mklp2 expression by cardiomyocytes in the left ventricular wall of preterm rats indicates acceleration of cardiomyocyte hypertrophy. Shorter duration of prenatal development is associated with more pronounced morphological and functional rearrangements in the rat myocardium.

Preterm rat survival is enhanced by gestational environmental enrichment

Throughout the last decade, the estimated global human preterm birth rate was 10.6 %, with higher rates in Asia, South America, and Africa. Preterm individuals, even in adulthood, are more likely to develop cardiorespiratory, renal, and metabolic disorders. On the other hand, when experimental animals are housed in an enriched environment during gestation, the development of the progeny in utero is accelerated, compared to standard housing conditions. By terminating gestation one and a half days before parturition, we investigated whether environmental enrichment restricted to gestation may have an impact on progeny survival. Our results demonstrate that the gestational enriched environment tripled the rat´s offspring survival, which was associated with decreased expression of anxiety-like behaviors in the pregnant mother. Sex of the offspring was not a factor in determining survival. We discuss the effect of increased secretion of various trophic factors and hormones induced by the enriched environment on progeny survival.

Characteristics of Myocardial Blood Vessels in Preterm Rats in the Late Postnatal Ontogeny.

Immunohistochemical study (CD31 detection) and morphometric analysis (evaluation of specific volumes of cardiomyocytes and blood capillaries, diameter of blood capillaries, trophic index, and pericapillary diffusion zone) of the left ventricular myocardium in preterm (12 h and 24 h preterm) Wistar rats was carried out on postnatal days 56 and 180. A decrease in the trophic index and an increase in the zone of pericapillary diffusion in the myocardium of the left ventricle in preterm rats were shown, which indicates deterioration of the heart supply during the postnatal ontogeny.

Nicotine ameliorates inflammatory mediators in RU486 induced preterm labor model through activating cholinergic anti-inflammatory pathway.

Preterm birth is a global public health threat. Inflammatory reaction is thought to mediate preterm birth. The role of nicotine, an anti-inflammatory agent that is mediated by cholinergic anti-inflammatory pathways (CAP), remains unclear in the pathogenesis. Pregnant rats were randomly divided into four groups (20 rats each): pregnant control group (P), RU486-treated group (PTL), RU486 and nicotine-treated group (PTL+N), RU486, nicotine and α-BGT treated group (PTL+N+A). Rats were administered RU486 (1.0mg/kg) by subcutaneous injection on gestational day (GD) 18 to establish PTL model. Subcutaneous injection of nicotine (1mg/kg) was administered daily from GD 16 to 18. α-BGT (1µg/kg) was administrated subcutaneously in two sessions and each session was 30min prior to nicotine. TNF-α, IL-1β, IL-4, IL-6, IL-10 in myometrium and serum were detected by Luminex. Macrophage infiltration and α7nAChR were detected by IHC. We established a RU486-induced preterm labor rat model. Preterm labor was associated with a striking upregulation inflammatory mediators and increased macrophage infiltration. Nicotine significantly prolonged gestation (P&lt;0.05) and α-BGT treatment reversed the prolonged interval (P&lt;0.05). The cytokines all markedly elevated at 12h, but deceased after delivery (P&lt;0.05). The IL-1β and TNF-α in serum were significantly increased in PTL group vs P group (P&lt;0.05), and decreased after nicotine treatment (P&lt;0.05). The cytokines IL-1β, IL-4, IL-6, IL-10 and TNF-α in myometrium increased as the same trend as in serum. Nicotine treatment also downregulated the expression of α7nAChR in pregnant tissue. We confirmed the increased inflammation in preterm birth. Nicotine was able to down-regulate the inflammatory mediates and prolong the pregnant duration in PTL model, which might be induced by activating α7nAChR through CAP. This study provides a novel evidence supporting the future development of therapeutic target for preterm birth.