Rat Placenta Research Articles

Protective Effects of Ascorbic Acid Against Cadmium-Induced Toxicity in the Placenta and Fetus of Rats.

This study aimed to determine the protective role of l-ascorbic acid in a pregnant rat model of cadmium-induced toxicity. Cadmium is a toxic heavy metal that can seriously harm placenta and fetus tissue in pregnant women. Forty-two healthy female Wistar albino rats (250-300 g weight and 14-16 weeks) were randomly distributed into six equal groups (n = 7): control, cadmium 1 mg (CD1), cadmium 5 mg (CD5), ascorbic acid (AA), CD1+AA, CD5+AA. Cadmium was administered to pregnant rats by oral gavage every other day, and/or AA (200 mg) was administered every day. At the end of pregnancy (Day 21), blood, placenta, and fetuses were collected from rats. The results indicated that cadmium-induced oxidative stress by increasing the level of MDA and by decreasing the levels of GSH, SOD, and CAT activity in the serum of maternal. However, AA administration significantly decreased MDA levels and increased GSH levels, SOD, and CAT activity (p < 0.05). Cadmium (5 mg/kg) exposure significantly increased creatinine levels compared to AA and CD1+AA groups (p < 0.05). In addition, AA (200 mg/kg) significantly attenuated cadmium-induced histopathological alteration in the placental and fetal tissues. In conclusion, AA may prevent cadmium toxicity in maternal and fetal tissues, as it regulates oxidative imbalance in pregnant rat tissues and alleviates histopathological changes.

Kefir peptides mitigate L-NAME-induced preeclampsia in rats through modulating hypertension and endothelial dysfunction

AimPreeclampsia is a complex and serious pregnancy disorder that leads to maternal and neonatal mortality worldwide. Kefir peptides (KPs), derived from various prebiotic fermentations in whole milk by kefir grains, were investigated for their potential therapeutic effects. In this study, we used the L-NAME in drinking water to induce a preeclampsia-like condition in spontaneous hypertension stroke-prone (SHRSP) pregnant rats. Main methodsThe rats were assigned to five groups: the normal group (WKY rats), the untreated group (SHRSP rat control pregnant), the L-NAME/Mock group (SHRSP rats fed with L-NAME water), the L-NAME/KPs-LD group (SHRSP rats fed with L-NAME water and low-dose KPs diets), and the L-NAME/KPs-HD group (SHRSP rats fed with L-NAME water and high-dose KPs diets) for a 20-day experiment. Chorioallantois membrane (CAM) assay was applied for ex vivo angiogenesis study of KPs treatment. Key findingsData showed that rats in the L-NAME group developed severe hypertension, proteinuria, placental damage, and embryo resorption. Pre-administration of KPs significantly reduced hypertension, proteinuria, improved generalized endothelial dysfunction, and decreased levels of anti-HIF-1α, sFLT1, anti-TNF-α, and IL-6 in the placenta of SHRSP rats. In ex vivo CAM study, L-NAME administration in chicken embryos resulted in lower vessel density and hemorrhage; however, angiogenesis was observed after KPs-HD treatment. SignificanceThe results indicate that kefir peptides improve renal lesions, prevent renal parenchyma damage, and balance endothelial and angiogenic dysfunction in both maternal and fetal sites in L-NAME-induced SHRSP pregnant rats.

Aromatase as a novel target of parabens in human and rat placentas: 3D-quantitative structure-activity relationship and docking analysis

Aromatase (CYP19A1), a pivotal enzyme in the biosynthesis of estradiol from testosterone, is predominantly expressed in reproductive tissues including placentas. This study investigated the effects of paraben acid and nine parabens on the activity of human and rat CYP19A1 using microsomes derived from human and rat placentas and on estradiol secretion in human choriocarcinoma BeWo cells. The results showed that propyl, butyl, hexyl, heptyl, and nonyl parabens significantly inhibited human CYP19A1 activity, with IC50 values of 66.37, 61.08, 55.65, 48.26, and 27.24 μM, respectively. In BeWo cells, these parabens notably diminished estradiol secretion at concentrations of 100 μM. Similarly, rat CYP19A1 was inhibited by these parabens, with IC50 values of 98.07, 70.10, 41.30, 27.93, and 6.33 μM for propyl, butyl, hexyl, heptyl, and nonyl parabens, respectively. Kinetic analysis identified these compounds as mixed inhibitors. Bivariate correlation analysis revealed a negative correlation between the partition coefficient value, molecular weight, the number of carbon atoms in the alcohol moiety, as well as heavy atom number and IC50 values. Three-dimensional quantitative structure-activity relationship analysis highlighted the critical role of hydrophobic regions in determining inhibitory potency. Docking studies suggested that parabens interact with the heme-iron binding site of both human and rat CYP19A1. This study elucidates the inhibitory effects of various parabens on CYP19A1 and their binding mechanisms, thereby providing a deeper understanding of their potential impact on estrogen biosynthesis.

Effects of Maternal Immune Activation on Tryptophan Metabolism in Rat Placenta and Decidua

Effects of Maternal Immune Activation on Tryptophan Metabolism in Rat Placenta and Decidua

The potential harmful effect of cyclophosphamide on the placenta in rats

The potential harmful effect of cyclophosphamide on the placenta in rats

Effect of fish oil supplementation on histological changes, apoptosis and oxidative stress of rat placenta against formaldehyde-induced toxicity

Formaldehyde (FA) as a common organic compound has been shown to cause placental dysfunction and fetal defects. The potential benefits of fish oil (FOil) in protecting placental structures are attributed to its antioxidant properties. This study aimed to explore the preventive role of FOil in mitigating the adverse effects of FA in pregnant rats. Thirty pregnant Wistar rats were randomly categorized into five groups of control, sham (Normal saline; Orally and intraperitoneally), FOil (0.5 ml/day; Orally), FA (5 mg/kg/bw; intraperitoneally), FA+FOil. The treatment period was from day 0–20 of pregnancy. On the 20th day of pregnancy, placental morphometric parameters were measured. The histological and histochemical analyses were performed using H&E and PAS staining, respectively. Also, the placenta tissue was analyzed for oxidative stress biomarkers, p-53 protein levels, and the expression of caspase-3 gene. The administration of FA led to a significant decrease in the weight, diameter, and thickness of the placenta, as well as a decrease in the thickness of the decidua layer, junctional and labyrinth zone, and the number of trophoblast giant cells in rat placentas. FA led to a significant increase in placental p-53 protein levels, caspase-3 expression, and oxidative stress biomarkers. Administration of FOil to pregnant rats treated with FA led to a significant decrease in morphometric and histological changes, oxidative stress, and the expression of genes associated with apoptosis. The findings suggest that the administration of FOil to FA-treated pregnant rats can protect placental histopathological changes by enhancing the activity of the antioxidant enzymes.

Core biomarkers analysis benefit for diagnosis on human intrahepatic cholestasis of pregnancy

BackgroundThe pregnant women with intrahepatic cholestasis were at high risk of fetal distress, preterm birth and unexpected stillbirth. Intrahepatic cholestasis of pregnancy (ICP) was mainly caused by disorder of bile acid metabolism, whereas the specific mechanism was obscure.MethodsWe performed proteomics analysis of 10 ICP specimens and 10 placenta specimens from patients without ICP through data-independent acquisition (DIA) technique to disclose differentially expressed proteins. We executed metabolomic analysis of 30 ICP specimens and 30 placenta specimens from patients without ICP through UPLC-MS/MS to identify differentially expressed metabolites. Enrichment and correlation analysis was used to obtain the direct molecular insights of ICP development. The ICP rat models were constructed to validate pathological features.ResultsThe heatmap of proteomics analysis showed the top 30 up-regulated and 30 down-regulated proteins. The metabolomic analysis revealed 20 richer and 4 less abundant metabolites in ICP samples compared with placenta specimens from patients without ICP, and enrichment pathways by these metabolites included primary bile acid biosynthesis, cholesterol metabolism, bile secretion, nicotinate and nicotinamide metabolism, purine metabolism and metabolic pathways. Combined analysis of multiple omics results demonstrated that bile acids such as Glycohyocholic acid, Glycine deoxycholic acid, beta-Muricholic acid, Noncholic acid, cholic acid, Gamma-Mercholic Acid, alpha-Muricholic acid and Glycochenodeoxycholic Aicd were significantly associated with the expression of GLRX3, MYL1, MYH7, PGGT1B, ACTG1, SP3, LACTB2, C2CD5, APBB2, IPO9, MYH2, PPP3CC, PIN1, BLOC1S1, DNAJC7, RASAL2 and ATCN3 etc. The core protein ACAT2 was involved in lipid metabolic process and animal model showed that ACAT2 was up-regulated in placenta and liver of pregnant rats and fetal rats. The neonates had low birth weight and Safranin O-Fast green FCF staining of animal models showed that poor osteogenic and chondrogenic differentiation of fetal rats.ConclusionMultiple metabolites-alpha-Muricholic acid, beta-Muricholic acid, Glycine deoxycholic acid and Glycochenodeoxycholic Acid etc. were perfect biomarkers to predict occurrence of ICP. Bile acids were significantly associated with varieties of protein expression and these proteins were differentially expressed in ICP samples. Our study provided several biomarkers for ICP detection and potential therapeutic targets for ICP development.

Gene expression of MCT8, D3 and TTR in rat placentas with early gestation

Gene expression of MCT8, D3 and TTR in rat placentas with early gestation

Spatial Activation of Autophagy in Human Placenta-Related Tissue During Labor: A Possible Mechanism for Labor Onset.

To explore the mechanisms of labor by investigating the autophagy of placental and fetal membranes tissue in normal pregnant women. Placenta and fetal membranes were collected from women with singleton pregnancies without any medical complications and from women who delivered vaginally (labor-initiated group; L group) or by caesarean section (labor-noninitiated group; NL group). Autophagosomes were observed by transmission electron microscopy (TEM). Immunofluorescence and western blotting (WB) were used to detect protein levels of the autophagy markers LC3A and LC3B. TEM, immunohistochemistry (IHC), and WB were used to compare autophagy in different parts of the placenta and fetal membranes in the L and NL groups. The expression of LC3B/LC3A, ROCK1, and ROCK2 in the placenta of nonpregnant and pregnant rats was detected by WB and IHC. TEM and IHC results showed an increase in the number of autophagosomes and autophagic lysosomes in the L group, and WB results indicated an increase in the LC3B/A ratio between the placenta and fetal membranes in the L group. Autophagy was significantly increased on the maternal side of the placenta in the L group, and the level of autophagy became higher near rupture in the fetal membranes and near the point where the umbilical cord joins the placenta in the L group. The LC3B/A ratio increased and ROCK1 and ROCK2 levels decreased in postnatal rats. Autophagy can occur in the placenta and fetal membranes and its activity is higher at the onset of labor, suggesting a role in labor.

Subclinical infection by lipopolysaccharide from E. coli alters vascular and inflammatory mediators in rat implantation sites and placentas

Subclinical infection by lipopolysaccharide from E. coli alters vascular and inflammatory mediators in rat implantation sites and placentas

Sex differences in gene expression of nutrient transporters in the placenta of rats subjected to high-intensity resistance training associated with an obesogenic diet

Sex differences in gene expression of nutrient transporters in the placenta of rats subjected to high-intensity resistance training associated with an obesogenic diet

ABC Efflux Transporters and Solute Carriers in the Early Developing Brain of a Marsupial Monodelphis domestica (South American Gray Short-Tailed Opossum).

This study used a marsupial Monodelphis domestica, which is born very immature and most of its development is postnatal without placental protection. RNA-sequencing (RNA-Seq) was used to identify the expression of influx and efflux transporters (ATP-binding cassettes [ABCs] and solute carriers [SLCs]) and metabolizing enzymes in brains of newborn to juvenile Monodelphis. Results were compared to published data in the developing eutherian rat. To test the functionality of these transporters at similar ages, the entry of paracetamol (acetaminophen) into the brain and cerebrospinal fluid (CSF) was measured using liquid scintillation counting following a single administration of the drug along with its radiolabelled tracer [3H]. Drug permeability studies found that in Monodelphis, brain entry of paracetamol was already restricted at P5; it decreased further in the first week of life and then remained stable until the oldest age group tested (P110). Transcriptomic analysis of Monodelphis brain showed that expression of transporters and their metabolizing enzymes in early postnatal (P) pups (P0, P5, and P8) was relatively similar, but by P109, many more transcripts were identified. When transcriptomes of newborn Monodelphis brain and E19 rat brain and placenta were compared, several transporters present in the rat placenta were also found in the newborn Monodelphis brain. These were absent from E19 rat brain but were present in the adult rat brain. These data indicate that despite its extreme immaturity, the newborn Monodelphis brain may compensate for the lack of placental protection during early brain development by upregulating protective mechanisms, which in eutherian animals are instead present in the placenta.

Prenatal aripiprazole induces alterations of rat placenta: a histological, immunohistochemical and ultrastructural study.

Antipsychotic drugs (APDs) are used to treat many psychiatric illnesses as schizophrenia. Typical antipsychotic drugs (TAPDs) are being used; however, they have many side effects. Atypical antipsychotic drugs (AAPDs) are newer medications with known fewer side effects. Aripiprazole (ARI) is an AAPD, recommended by healthcare providers, even during pregnancy. It can cross the placental barrier and enter fetal circulation, so it might be possible that ARI can adversely impair normal placental development and growth, if it is given prenatally. ARI was applied orally to pregnant female rats in two doses (3& 6mg/kg body weight). On gestation day 20, the mothers were sacrificed, and the placentas were removed and processed for general histological and electron microscopic evaluations. Immunohistochemistry was done using anti-PCNA (proliferating cell nuclear antigen), anti-Bax (for apoptosis) and anti-vascular endothelial growth factor alpha (VEGFA). Morphological evaluation revealed degenerative changes in the placenta as dark nuclei, vacuolization, and cyst formation. Ultra-structurally, there was degeneration of cellular components including organelles and nuclei. These changes were found in different cells of the basal and labyrinth zones and were dose dependent. Immunohistochemistry revealed upregulation of Bax and VEGFA and downregulation of PCNA. Prenatal administration of the AAPD, ARI to pregnant female rats resulted in histological changes in the placenta. Additionally, there was a decrease in cellular proliferation and increase in apoptosis, and vascular impairment. This indicates placental atrophy and dysgenesis and might suggest possible teratogenic effects to ARI, which needs further evaluation.

Exposure to Extracellular Mitochondrial DNA During Pregnancy Induces a Pro-Inflammatory Response in Rat Placenta

Introduction: Mitochondrial DNA (mtDNA) is released in the cytosol or the extracellular space due to mitochondrial dysfunction or cell death. Extracellular mtDNA is recognized by the innate immune receptor Toll-like receptor 9 (TLR9) and induces pro-inflammatory and immunogenic responses. Circulating cell-free mtDNA (ccf-mtDNA) increases with advancing gestational age and abnormal concentrations have been reported in obstetric complications such as preeclampsia (PE). Placentas from women with PE exhibit signs of extensive inflammation; however, the contribution of ccf-mtDNA to placental inflammation during pregnancy has not been investigated. We hypothesized that in vivo exposure to extracellular mtDNA during pregnancy would induce an inflammatory response in rat placenta via activation of TLR9 signaling. Methods: We isolated mtDNA from liver of Sprague Dawley pregnant rats (gestational day: 14-15, term=22-23 days) and treated gestational age-matched dams with mtDNA (350ng/kgBW) or saline (control) via intravenous injection. Following 4 hours after treatment, maternal organs and fetoplacental units were collected and gene expression of cytokines and TLR9 were measured. Results: Plasma levels of mtDNA 4 hours after treatment were not different between saline and mtDNA-treated rats (2−ΔCT, median (IQR); saline: 2.75 (1.61) vs. mtDNA: 2.64 (1.29), p&gt;0.05). Treatment with mtDNA increased mRNA expression of pro-inflammatory tumor necrosis factor-alpha (TNF-α) (saline: 0.65 (1.1) vs. mtDNA: 2.84 (1.9), p=0.015), interleukin (IL)-6 (saline: 0.32 (0.2) vs. mtDNA: 3.37 (4.3), p=0.008), and IL-1β (saline: 0.2 (0.93) vs. mtDNA: 4.7 (6.0), p=0.01) and decreased expression of anti-inflammatory IL-10 (saline: 1.6 (0.8) vs. mtDNA: 0.6 (0.8), p=0.001) in rat placentas. Expression of macrophage marker F4/80 (saline: 0.4 (1.0) vs. mtDNA: 2.41 (4.7), p=0.04) and monocyte chemoattractant protein-1 (MCP-1) (saline: 0.68 (0.54) vs. mtDNA: 2.0(1.96), p=0.041) also increased in rat placentas in response to mtDNA treatment. To assess whether this inflammatory response was tissue-specific, we evaluated mRNA expression of inflammatory genes in maternal kidneys. Treatment with mtDNA increased the levels of IL-1β (2−ΔCT, median (IQR); saline: 1.05 (1.1) vs. mtDNA: 10.17 (8.0), p=0.008) and IL-6 (saline: 0.98 (1.76) vs. mtDNA: 6.8 (3.5), p=0.002). mtDNA treatment did not affect kidney TNF-α and IL-10 expression (p&gt;0.05). In contrast, expression of F4/80 (saline: 0.87 (2.2) vs. mtDNA: 12.5 (12.4), p=0.003) and MCP-1 (saline: 0.9 (1.7) vs. mtDNA: 7.4 (8.3), p=0.011) was greater in maternal kidneys from mtDNA-treated rats vs. controls. TLR9 expression increased in placentas (saline: 1.29 (0.5) vs. mtDNA: 4.0 (7.8), p&lt;0.0001) and maternal kidneys (saline: 1.2 (1.8) vs. mtDNA: 4.7 (4.6), p=0.045) in response to mtDNA treatment. Conclusion: Exposure to an in vivo challenge with extracellular mtDNA during pregnancy induces a pro-inflammatory response in placentas and kidneys from pregnant rats. These responses may be mediated by TLR9 signaling activation. NIH R01-HL0146562. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Hypoxia and oxidative stress impair autophagy and cell death mechanisms in trophoblast cells and reduce placental effciency in rodents

Introduction: Hypoxia and oxidative stress can activate autophagy, a lysosomal degradation pathway that maintains cellular homeostasis. Impairments in autophagy mechanisms have been observed in placentas from obstetric complications associated with placental hypoxia and oxidative stress, such as preeclampsia and intrauterine growth restriction. The objective of this study was to investigate the effects of hypoxia and oxidative stress on placental cell autophagy. We hypothesized that exposure to oxidative stress and hypoxia would alter the balance between cytotoxic and cytoprotective mechanisms in human trophoblast cells and rat placentas and would adversely affect placental effciency. Methods: We used an in vitro model incorporating human trophoblast cells (BeWo cells) exposed to an oxidative stressor, antimycin A (10, 100, 320 μM) or vehicle for 4 hours. Trophoblast cell death and autophagy mechanisms were assessed via flow cytometry and western blotting. Additionally, we used a rodent model of gestational sleep apnea, a pregnancy complication associated with placental hypoxia. Long Evans timed-pregnant dams were exposed to chronic intermittent hypoxia (CIH; n=6-8) or normoxia (NX; n=8-9) during their sleep cycle from gestational day (GD) 15 to 20 (term=21-23 days). Results: In trophoblast cells (n=5-9 independent experiments), antimycin A increased necrosis and LC3 A/B II/I ratio (autophagy marker) at 100 μM compared to vehicle (p≤0.015). At antimycin A 320 μM, necrosis remained elevated, while BAX (pro-apoptotic marker) and p62 (autophagosomal flux marker) were reduced compared to vehicle (p&lt;0.0001), and LC3 A/B II/I ratio returned to vehicle levels (p&gt;0.05 vs. vehicle). Placental weights from CIH exposed dams were greater (NX: 0.51±0.02 g vs. CIH: 0.60±0.03 g, p=0.015) and fetal to placental weight ratios (marker of placental effciency) were reduced compared to control pregnancies (NX: 5.25±0.13 vs. CIH: 4.43±0.14, p=0.0006) on GD20. Gestational CIH did not affect (p&gt;0.05) fetal weights (NX: 2.76±0.06 g vs. CIH: 2.61±0.06 g), crown to rump length (NX: 3.32±0.03 cm vs. CIH: 3.18±0.12 cm), abdominal girth (NX: 3.22±0.06 cm vs. CIH: 3.32±0.12 cm), or litter size (NX: 11.9±0.90 vs. CIH: 10.5±0.82). Conclusion: Oxidative stress alters the balance between cytotoxic and cytoprotective mechanisms in trophoblast cells, promoting cell necrosis. Although assessment of autophagy machinery and cell death in placentas from hypoxic pregnancies is ongoing, our results indicate that gestational CIH adversely affects placental effciency. NIH R01 HL146562, AHA 22PRE-900431, T32 AG020494, AHA 22POST-903250. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Histological Assessment of Placental Development Following Intrauterine Exposure to Caffeine in Adult Wistar Rats

In recent years, there have been concerns about human reproductive disorders. Physiological adaptations are crucial for optimal fetal development during pregnancy. The widespread consumption of caffeine by pregnant women raises questions about its impact on maternal physiology and fetal development. Hence, the objective of this study was to evaluate the histological assessment of placenta development following intrauterine exposure to caffeine in adult Wistar rats using appropriate standard techniques. On each gestational day (GD13, GD15, GD17, and GD19), five (5) animals were sampled from each group and their placentas were harvested for histological assessment. The Maternal weight, Fetal Crown Rump Length, Placental weight, Placental diameter major, Placental diameter minor, and fetal weight were taken on the harvested placenta. Results showed varying alterations in the histomorphology of the placenta ranging from delayed differentiation of glycogen cells, dilated and congested blood vessels, vacuolar degeneration of glycogen cell islands, poor development of the labyrinth zone, and dilated fetal capillaries. In conclusion, there is histomorphological evidence that caffeine administration has deleterious effects on the development of the placenta in Wistar rats.

CPEB2 inhibits preeclampsia progression by regulating SSTR3 translation through polyadenylation

AimsTrophoblast cell dysfunction is one of the important factors leading to preeclampsia (PE). Cytoplasmic polyadenylation element-binding 2 (CPEB2) has been found to be differentially expressed in PE patients, but whether it mediates PE process by regulating trophoblast cell function is unclear. MethodsThe expression of CPEB2 and somatostatin receptor 3 (SSTR3) was detected by quantitative real-time PCR, Western blot (WB) and immunofluorescence staining. Cell functions were analyzed by CCK-8 assay, EdU assay, flow cytometry and transwell assay. Epithelial-mesenchymal transition (EMT)-related protein levels were detected by WB. The interaction of CPEB2 and SSTR3 was confirmed by RIP assay, dual-luciferase reporter assay and PCR poly(A) tail assay. Animal experiments were performed to explore the effect of CPEB2 on PE progression in vivo, and the placental tissues of rat were used for H&E staining, immunohistochemical staining and TUNEL staining. ResultsCPEB2 was lowly expressed in PE patients. CPEB2 upregulation accelerated trophoblast cell proliferation, migration, invasion and EMT, while its knockdown had an opposite effect. CPEB2 bound to the CPE site in the 3′-UTR of SSTR3 mRNA to suppress SSTR3 translation through reducing poly(A) tails. Besides, SSTR3 overexpression suppressed trophoblast cell proliferation, migration, invasion and EMT, while its silencing accelerated trophoblast cell functions. However, these effects could be reversed by CPEB2 upregulation and knockdown, respectively. In vivo experiments, CPEB2 overexpression relieved histopathologic changes, inhibited apoptosis, promoted proliferation and enhanced EMT in the placenta of PE rat by decreasing SSTR3 expression. ConclusionCPEB2 inhibited PE progression, which promoted trophoblast cell functions by inhibiting SSTR3 translation through polyadenylation.

PPARγ alleviates preeclampsia development by regulating lipid metabolism and ferroptosis

The study aims to explore the effect of PPARγ signaling on ferroptosis and preeclampsia (PE) development. Serum and placental tissue are collected from healthy subjects and PE patients. The PPARγ and Nrf2 decreases in the PE. Rosiglitazone intervention reverses hypoxia-induced trophoblast ferroptosis and decreases lipid synthesis by regulating Nfr2 and SREBP1. Compared to the Hypoxia group, the migratory and invasive abilities enhance after rosiglitazone and ferr1 treatment. Rosiglitazone reduces the effect of hypoxia and erastin. The si-Nrf2 treatment attenuats the effects of rosiglitazone on proliferation, migration, and invasion. The si-Nrf2 does not affect SREBP1 expression. PPARγ agonists alleviates ferroptosis in the placenta of the PE rats. The study confirms that PPARγ signaling and ferroptosis-related indicators were dysregulated in PE. PPARγ/Nrf2 signaling affects ferroptosis by regulating lipid oxidation rather than SREBP1-mediated lipid synthesis. In conclusion, our study find that PPARγ can alleviate PE development by regulating lipid oxidation and ferroptosis.

Effect of Morinda citrifolia (Noni) Fruit Extract on the Teratogenecity in Female Wistar Rats

The raw fruit extract of Morinda citrifolia plant and its commercially available formulation in the market as Noni max (Best-selling brand of Brihans pharmaceutical in India and abroad) were obtained from Brihans Pharmaceuticals Pvt. Ltd. Mulund, Mumbai, India. 80 Wistar rats of either sex weighing between 200 to 250 gms were used for experimentation. In the present study, it was found that the Morinda citrifolia fruit extract and its formulation found safe for the developmental stages of foetus. It was also found that there was no significant difference was noted in body weight and the relative weight of the ovary, uterus and placenta of female rat. There was no structural and functional manifestation was noted in the developing foetusin the pregnant female rats. From the present study it is confirm that, both Morinda citrifolia fruit extract and its formulation (Noni max) did not produce any teratogenic effect in rats up to 1000 mg/kg and 40 ml/kg respectively.

Developmental expression of catecholamine system in the human placenta and rat fetoplacental unit

Catecholamines norepinephrine and dopamine have been implicated in numerous physiological processes within the central nervous system. Emerging evidence has highlighted the importance of tightly regulated monoamine levels for placental functions and fetal development. However, the complexities of synthesis, release, and regulation of catecholamines in the fetoplacental unit have not been fully unraveled. In this study, we investigated the expression of enzymes and transporters involved in synthesis, degradation, and transport of norepinephrine and dopamine in the human placenta and rat fetoplacental unit. Quantitative PCR and Western blot analyses were performed in early-to-late gestation in humans (first trimester vs. term placenta) and mid-to-late gestation in rats (placenta and fetal brain, intestines, liver, lungs, and heart). In addition, we analyzed the gene expression patterns in isolated primary trophoblast cells from the human placenta and placenta-derived cell lines (HRP-1, BeWo, JEG-3). In both human and rat placentas, the study identifies the presence of only PNMT, COMT, and NET at the mRNA and protein levels, with the expression of PNMT and NET showing gestational age dependency. On the other hand, rat fetal tissues consistently express the catecholamine pathway genes, revealing distinct developmental expression patterns. Lastly, we report significant transcriptional profile variations in different placental cell models, emphasizing the importance of careful model selection for catecholamine metabolism/transport studies. Collectively, integrating findings from humans and rats enhances our understanding of the dynamic regulatory mechanisms that underlie catecholamine dynamics during pregnancy. We identified similar patterns in both species across gestation, suggesting conserved molecular mechanisms and potentially shedding light on shared biological processes influencing placental development.