First Day Of Gestation Research Articles

Gestational GenX and PFOA exposures induce hepatotoxicity, metabolic pathway, and microbiome shifts in weanling mice

Ammonium perfluoro (2-methyl-3-oxahexanoate) (GenX), a replacement for perfluorooctanoic acid (PFOA), has been detected in multiple environmental media and biological samples worldwide. Accumulated evidence implies that GenX exposure might exert adverse health effects, although the underlying mechanisms have not been fully revealed. In this study, pregnant BALB/c mice were exposed to GenX (2 mg/kg/day), PFOA (1 mg/kg/day), or Milli-Q water by gavage from the first day of gestation (GD0) until GD21. Necropsy and tissue collection were conducted in pups at 4 weeks of age. PFOA and GenX induced similar histopathological changes in both the liver and the intestinal mucosa, accompanied by higher serum levels of alanine and aspartate aminotransferase. Moreover, the capacity of hepatic glycogen storage and intestinal mucus secretion were significantly decreased, suggesting dysfunction of liver metabolism and the intestinal mucosal barrier. A total of 637 and 352 differentially expressed genes (DEGs) were identified in the liver tissues of GenX and PFOA group, respectively. Most of the enriched pathways from the DEGs by KEGG enrichment analysis were metabolism-associated. Moreover, overexpression of CYP4A14, Sult2a1, Cpt1b, Acaa1b, Igfbp1, Irs-2 and decreased expression of Gys2 were observed in livers of GenX exposed pups, supporting the hypothesis that there was metabolic disruption. Furthermore, DNA damage and cell cycle arrest proteins (Gadd45β, p21, Ppard) were significantly increased, while cell proliferation-related proteins (Cyclin E, Myc, EGFR) were decreased by gestational GenX exposure in the pups' liver. In addition, imbalance of gut microbiota and dysfunction of the intestinal mucosa barrier might contribute to hepatotoxicity at least in part. Taken together, our results suggested that gestational GenX exposure triggered metabolic disorder, which might be responsible for the hepatotoxicity in the pups in addition to dysfunction of the intestinal mucosa barrier. This study enriches the mechanisms of GenX-induced developmental hepatotoxicity by associating metabolic disorder with intestinal homeostasis.

HISTOLOGICAL EFFECTS OF CITRUS AURANTIFOLIA ON GRAVID AND POST-PARTUM UTERUS

Diseases have afflicted man for ages but humans always make effort to remedy the situation in order to regain a life disturbed by these ailments. The earliest form of healing substances had been Traditional (herbal) medicines, but with the advent of civilization which had led to better scientific understanding of diseases and medications, orthodox medicines have become the main and well recognized products for the management of diseases in modern health systems. The aim of this study was to investigate the effects of citrus aurantifolia (lime plant) on gravid and non-gravid uterus of female wistar rats and their pups. A total of 50 Wistar rats were used in carrying out the experiment and classified into two Models. Each group in Model 1 contained 8 rats each, while in the Model 2, each group comprised 5 rats. The body weight of the rats were measured and recorded weekly. Group I-III in model 1 received 1ml/kg, 1.5 ml/kg and 2 ml/kg respectively, two rats from each group were euthanized at 7, 14 and 21 days to observe acute, subacute and chronic effect, group IV (control) received food and distilled water only. While in model 2, group I rats commenced 1 ml/kg of aqueous lime juice from the first day of gestation, group II received 1 ml/kg of aqueous lime 1week after gestation and group III were administered food and water. The histomorphological study of the uterus revealed deleterious effect of lime juice in a dose dependent pattern and Hormonal assay carried out showed a reduction in gonadotrophin level. In conclusion, high consumption of Lime juice compromises the outcome of pregnancy in the treated rats by the reduction in the crown rump length and weight of pups.

Effects of choline supplementation in mothers with hypothyroidism on the brain-derived neurotrophic factor gene expression changes in pre-pubertal offspring rats.

Thyroid hormones play a vital function in the maturation in the course of mind development. Regarding the well-known effects of choline on brain-derived neurotrophic factor (BDNF), the study examined the effects of choline on hippocampal BDNF gene expression in maternal hypothyroidism rats. To induce the hypothyroidism, 6-propyl-2-thiouracil was introduced to the ingesting water from the sixth day of gestation to twenty-first postnatal day (PND). Choline-treatment started twice a day on the first day of gestation until PND 21. On PND28, pups were sacrificed. The expression of BDNF gene was evaluated after the hippocampus was harvested. Our results demonstrated that both male and female pre-pubertal offspring rats' BDNF gene expression was decreased by developmental hypothyroidism. Choline increases the ratio of relative gene expression of BDNF in the hippocampus of males and females in the control/hypothyroidism group, especially in males. It can be concluded that maternal choline supplementation on the first day of gestation until PND 21 improves brain development and cognitive function in pre-pubertal offspring rats regarding control/hypothyroidism groups.

Is in-utero exposure to cannabis associated with the risk of attention deficit with or without hyperactivity disorder? A cohort study within the Quebec Pregnancy Cohort

Importance and objectivePrenatal cannabis effect on attention deficit with or without hyperactivity disorder (ADHD) remains to be determined. Our aim is to quantify the impact of in-utero exposure to cannabis...

Maternal Fluoride Exposure Exerts Different Toxicity Patterns in Parotid and Submandibular Glands of Offspring Rats.

There is currently a controversial and heated debate about the safety and ethical aspects of fluoride (F) used for human consumption. Thus, this study assessed the effects of prenatal and postnatal F exposure of rats on the salivary glands of their offspring. Pregnant rats were exposed to 0, 10, or 50 mg F/L from the drinking water, from the first day of gestation until offspring weaning (42 days). The offspring rats were euthanized for the collection of the parotid (PA) and submandibular (SM) glands, to assess the oxidative biochemistry and to perform morphometric and immunohistochemical analyses. F exposure was associated with a decrease in the antioxidant competence of PA in the 10 mg F/L group, contrasting with the increase observed in the 50 mg F/L group. On the other hand, the antioxidant competence of the SM glands was decreased at both concentrations. Moreover, both 10 and 50 mg F/L groups showed lower anti-α-smooth muscle actin immunostaining area in SM, while exposure to 50 mg F/L was associated with changes in gland morphometry by increasing the duct area in both glands. These findings demonstrate a greater susceptibility of the SM glands of the offspring to F at high concentration in comparison to PA, reinforcing the need to adhere to the optimum F levels recommended by the regulatory agencies. Such findings must be interpreted with caution, especially considering their translational meaning.

The effects of long-term doppler ultrasound exposure in the prenatal period on renal tissue physiology in rats

ABSTRACT Doppler ultrasonography (DUSG) is widely used for fetal evaluations. This study investigated the effects of new generation Doppler ultrasound application at different frequencies during pregnancy on postnatal renal development. Six pregnant female rats were divided into three groups. No procedure was performed on the first (control) group. In the second group, transabdominal DUSG was performed continuously for 15 min every day from the first day of gestation until birth. In the third group, DUSG was applied for 15 min every two days. Twenty-four male pups were sacrificed after 60 days. Renal tissues were then collected and subjected to biochemical, histopathological, and immunohistochemical evaluation. Malondialdehyde, glutathione, urea, Ca, K, and Cl levels increased in the DUSG groups compared to the control group (p < .05). Histopathologically, tubular damage increased in the DUSG groups compared to the control group (p < .05). Immunohistochemically, an increase was determined in Caspase-3 expression in the DUSG groups compared to the control group (p > .05). The DUSG groups also exhibited an increase in the superficial areas of the proximal and distal tubules, although the difference compared to the control group was not significant (p > .05). Multiple administrations of new generation DUSG to pregnant rats resulted in deleterious effects on the development of postnatal renal tissue. This shows that DUSG should be applied for as short a time as possible and that re-exposure should be avoided.

Maternal ethanol exposure induces behavioral deficits through oxidative stress and brain-derived neurotrophic factor interrelation in rat offspring.

Alcohol consumption during pregnancy damages the central nervous system of developing fetus and results in persistent physical and neurobehavioral abnormalities, including learning and memory disorders. The hippocampus which is involved in learning and memory is highly susceptible to the ethanol neurotoxic effects. Oxidative stress is one of the mechanisms in alcohol-induced disorders. Ethanol also interferes with the brain-derived neurotrophic factors (BDNF) expression. Using vitamin E as a potent antioxidant, we studied the possible interrelation between oxidative stress and BDNF on cognition. Ethanol (4 g/kg) and vitamin E (100, 200, and 400 mg/kg) were given to pregnant Wistar rats on first day of gestation (GD) until weaning (28 days). Oxidative stress marker, BDNF expression, and cyclic AMP-response binding-protein (CREB) expression levels were measured on postnatal days (PND) 28. Object location memory (OLM) was evaluated on PND 34. Our results demonstrated that ethanol exposure significantly reduced glutathione peroxidase (GPx) activity, reduced glutathione (GSH), reduced/oxidized glutathione (GSH/GSSG) ratio, and increased superoxide dismutase (SOD) activity, malondialdehyde (MDA) levels, and carbonyl protein content in the hippocampus. Total BDNF, BDNF mRNA, and CREB expression significantly reduced in the hippocampus by ethanol exposure. Also, ethanol significantly reduced the discrimination index (DI) in the OLM test. In addition, vitamin E administration could reduce oxidative stress, increase significantly BDNF and CREB levels, and improve cognitive dysfunction induced by ethanol exposure. Collectively, results suggest that probably oxidative stress can interrelate with the BDNF system for modulating cognitive function in the ethanol-exposed rat.

Effects of Pregabalin on Postnatal Development of The Kidney in Albino Rat’s Offsprings

ABSTRACTBackground: Pregabalin is used for the treatment of neuropathic pain, fibromyalgia, and migraine. Objectives: This study was designed to assess the effect of pregabalin on the developing kidney of albino rat’s offspring. Material and methods: Twenty pregnant rats were divided into two equal groups: group I (control) group and group II (treated) group which received pregabalin (150 mg/kg/day) from the first day of gestation up to 21 days after delivery. Offsprings were selected to be sacrificed on the 2nd postnatal day and at the 21st postnatal day, kidney specimens were prepared for light and electron microscopic examination. Results: Maternal pregabalin administration disrupted the development of the kidney in offspring with a significant increase in urea and creatinine level. Histological examination of the kidney offsprings at the 2nd postnatal day revealed irregular thickening of the glomerular basement membrane, fusion, and effacement of podocyte’s foot processes, and tubulointerstitial injury. Examination of the kidney offsprings at the 21st postnatal day revealed thickened distorted glomerular basement membrane, broadening, and fusion of the foot processes, and vacuolar degeneration of tubules. Conclusion: Maternal pregabalin might disturb the renal development in the offspring. So, it should be used with caution during pregnancy and lactation.

Efeito do extrato de Anacardium occidentale L. durante a gestação, lactação e no desenvolvimento da prole de ratos

Anacardium occidentale L. é uma espécie arbórea, pertencente à família Anacardiaceae, encontrada em muitos países. No Brasil, é conhecida popularmente como “cajueiro”, “cajueiro roxo”, sendo considerada uma espécie nativa brasileira que apresenta ampla distribuição em todo o território nacional. Portanto, o objetivo deste estudo foi avaliar o efeito do tratamento materno com o extrato de A. ocidentale na toxicidade materna e no desenvolvimento pós-natal da prole de ratos. Procedeu-se o estudo fitoquímico preliminar da planta, no qual realizaram-se testes qualitativos para identificação de alcalóides, flavonoides e taninos através de reações clássicas de coloração e precipitação. Foram utilizadas ratas fêmeas primíparas, da linhagem Wistar, com idade entre 90 e 120 dias, e peso de 200 ± 50g. As ratas foram acasaladas por 24 horas, sendo uma fêmea para cada macho. Após a confirmação da prenhez, as ratas gestantes foram alojadas em gaiolas-maternidade individuais, divididas aleatoriamente em dois grupos: Grupo CONTROLE (n=9) que recebeu água destilada por gavagem; e grupo EXTRATO (n=9), que recebeu a dose de 100mg/kg do extrato bruto do Anacardium occidentale, por meio de gavagem do primeiro dia de gestação até o final da lactação. Durante a gestação, foram avaliados os sinais de toxicidade das progenitoras e o desenvolvimento somático e físico da prole. Os resultados deste estudo apontam que a administração do extrato hidroalcóolico da folha do cajueiro roxo afetou o desenvolvimento físico e somático da prole, sugerindo efeito tóxico neonatal. Além disso, esse extrato também induziu toxicidade materna sistêmica, caracterizado pela presença de sinais clínicos de toxicidade.

Early exposure of pregnant women to non-steroidal anti-inflammatory drugs delivered outside hospitals and preterm birth risk: nationwide cohort study.

ObjectiveTo assess the risk of preterm birth associated with nonsteroidal anti‐inflammatory drugs (NSAIDs), focusing on early exposure in the period from conception to 22 weeks of gestation (WG).DesignNational population‐based retrospective cohort study.SettingThe French National Health Insurance Database that includes hospital discharge data and health claims data.PopulationSingleton pregnancies (2012–2014) with a live birth occurring after 22WG from women between 15 and 45 years old and insured the year before the first day of gestation and during pregnancy were included. We excluded pregnancies for which anti‐inflammatory medications were dispensed after 22WG.MethodsThe association between exposure and risk of preterm birth was evaluated with GEE models, adjusting on a large number of covariables, socio‐demographic variables, maternal comorbidities, prescription drugs and pregnancy complications.Main outcome measuresPrematurity, defined as a birth that occurred before 37WG.ResultsAmong our 1 598 330 singleton pregnancies, early exposure to non‐selective NSAIDs was associated with a significantly increased risk of preterm birth, regardless of the severity of prematurity: adjusted odds ratio (aOR) = 1.76 (95% CI 1.54–2.00) for extreme prematurity (95% CI 22–27WG), 1.28 (95% CI 1.17–1.40) for moderate prematurity (28–31WG) and 1.08 (95% CI 1.05–1.11) for late prematurity (32–36WG), with non‐overlapping confidence intervals. We identified five NSAIDs for which the risk of premature birth was significantly increased: ketoprofen, flurbiprofen, nabumetone, etodolac and indomethacin: for the latter, aOR = 1.92 (95% CI 1.37–2.70) with aOR = 9.33 (95% CI 3.75–23.22) for extreme prematurity.ConclusionOverall, non‐selective NSAID use (delivered outside hospitals) during the first 22WG was found to be associated with an increased risk of prematurity. However, the association differs among NSAIDs.Tweetable abstractFrench study for which early exposure to non‐selective NSAIDs was associated with increased risk of prematurity.

Neuroprotective potentials of Lycopersicon esculentum fruit extract on cadmium-induced toxicity in postnatal developing cerebellum of rats

The neuroprotective potemtials of Lycopersicon esculentum fruit extract on cadmium-induced oxidative stress in postnatal developing cerebellum of rats. Twenty-five pregnant Wistar rats (110-200g) were divided into five groups (n=5) and used for the experiment. Group I served as control and received water, Group II received 0.5mg/kg of Cadmium only, Group III received 50mg/kg aqueous extract of Lycopersicon esculentum only, Group IV received 0.5mg/kg body weight of cadmium+50mg/kg aqueous extract of Lycopersicon esculentum and Group V received 0.5mg/kg of cadmium +200mg/kg of vitamin C, orally from the first day of gestation to postnatal day 21. Lycopersicon esculentum was administered one hour before the administration of cadmium. Neurobehavioural tests was done on the pups of day 21. Then, pups of day 1, 7, 14, 21, and 28 were weighed, sacrificed and their brains dissected out, weighed with the cerebellum preserved for biochemical and histomorphological evaluations. Data were analysed using ANOVA at p &lt; 0.05. Cadmium-treated rats showed significant decreased in body and brain weight, decreased time spent on the forelimb grip, increased negative geotaxis, increased lipid peroxidation (LPO), and decreased glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) in the developing cerebellum. Histologically, there was persistent external granular layer (EGL), reduced molecular layer (ML) thickness and increased astrocytes population in the cerebellar cortex of cadmium-treated day 21pups. Lycopersicon esculentum extract and vitamin C reversed the behavioural and morphological alterations induced by cadmium toxicity. Cadmium-induced oxidative stress, behavioural deficit and morphological alterations in the postnatal developing cerebellum of rat was ameliorated by Lycopersicon esculentum fruit extracts as such may be a potential neuroprotective agent.&#x0D; Key words: Cadmium - oxidative stress - Lycopersicon esculentum – Neurobehaviour - Developing cerebellar cortex

Lead-induced oxidative stress in postnatal developing cerebellum of Wistar rats: role of aqueous extract of Cucumis sativus Linn and vitamin C

Lead (Pb) is one of the most abundant heavy metal whose toxicity causes environmental and health problems, with the brain being highly sensitive to lead toxicity. There is limited literature regarding the protection of the developing brain against lead-induced toxicity. However, plant-derived products with antioxidant activity have been useful in reducing lead-induced neurotoxicity. This study investigated the role of Cucumis sativus (C. sativus) (Cucumber) and vitamin C in lead-induced oxidative stress in postnatal developing cerebellum of Wistar rats. Twenty-five pregnant Wistar rats weighing between 160 and 180g were divided into five groups (n=5). Group I served as control and received water, group II received 50mg/kg of lead acetate, group III received 200mg/kg aqueous extract of C. sativus, group IV received 200mg/kg of C. sativus and 50mg/kg of lead acetate and group V received 200mg/kg of vitamin C and 50mg/kg of lead acetate. The interventions were administered orally using an oral gavage from the first day of gestation to postnatal day 21. Neurobehavioural assessment (forelimb grip strength and negative geotaxis) was carried out on pups of day 21 and then sacrificed. Some cerebella of pups of days 1, 7, 14, 21 and 28 were fixed in 10% formol-saline for histological and immunohistochemical evaluations, while others (day 21) were preserved in in phosphate buffered saline at 4°C and pH 7.2 for oxidative stress assays. Data were analysed using ANOVA at p&lt;0.05. Decreased body weight of Pb-treated pups on days 14 and 21, decreased forelimb grip and increased negative geotaxis, increased lipid peroxidation (LPO), decreased glutathione (GSH) levels, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities was seen in the lead-treated day 21 pups compared with the control and other treated groups. Histologically, in the cerebellar cortex, there was persistent external granular layer (EGL) on day 21 in the treated groups compared with the control, decreased molecular layer (ML) thickness and depleted Pc in the Pb-treated day 28 pups, and increased astrocyte population on day 21 pups compared with the control and C. sativus groups. Lead induced oxidative stress which caused behavioural deficit and morphological changes in the postnatal developing cerebellum of rats. Aqueous extracts of Cucumis sativus and vitamin C decreased the rate at which lead induced neurotoxicity.

Pre- and Neonatal Exposure to Lead (Pb) Induces Neuroinflammation in the Forebrain Cortex, Hippocampus and Cerebellum of Rat Pups.

Lead (Pb) is a heavy metal with a proven neurotoxic effect. Exposure is particularly dangerous to the developing brain in the pre- and neonatal periods. One postulated mechanism of its neurotoxicity is induction of inflammation. This study analyzed the effect of exposure of rat pups to Pb during periods of brain development on the concentrations of selected cytokines and prostanoids in the forebrain cortex, hippocampus and cerebellum. Methods: Administration of 0.1% lead acetate (PbAc) in drinking water ad libitum, from the first day of gestation to postnatal day 21, resulted in blood Pb in rat pups reaching levels below the threshold considered safe for humans by the Centers for Disease Control and Prevention (10 µg/dL). Enzyme-linked immunosorbent assay (ELISA) method was used to determine the levels of interleukins IL-1β, IL-6, transforming growth factor-β (TGF-β), prostaglandin E2 (PGE2) and thromboxane B2 (TXB2). Western blot and quantitative real-time PCR were used to determine the expression levels of cyclooxygenases COX-1 and COX-2. Finally, Western blot was used to determine the level of nuclear factor kappa B (NF-κB). Results: In all studied brain structures (forebrain cortex, hippocampus and cerebellum), the administration of Pb caused a significant increase in all studied cytokines and prostanoids (IL-1β, IL-6, TGF-β, PGE2 and TXB2). The protein and mRNA expression of COX-1 and COX-2 increased in all studied brain structures, as did NF-κB expression. Conclusions: Chronic pre- and neonatal exposure to Pb induces neuroinflammation in the forebrain cortex, hippocampus and cerebellum of rat pups.

Uterine and umbilical resistance index and fetal heart rate in pregnant bitches of different body weight

The aim of this study was to compare uterine and umbilical artery blood flow and fetal heart rate (FHR) in small, medium and large body weight (BW) dogs during the second half of pregnancy. Purebred pregnant bitches were assigned to one of the following groups according to their BW: small (S; ≤10 kg), medium (M; 11−25 kg) and large (L; >25−45 kg). Uterine and umbilical Doppler and M-mode ultrasonography was conducted every 10 days from Day 30–60 (Day 0 = first day of gestation). From Day 40, uterine and umbilical artery resistance index (RI) progressively and differentially decreased in the three groups (P < 0.01) being less in L than S bitches (P < 0.01). Litter size but not maternal BW (P > 0.1) affected uterine RI on Days 40 (r = 0.39; P < 0.01) and 50 (r = 0.41; P < 0.01). Conversely, on Day 60, maternal BW (r = 0.61; P < 0.01) had an effect on uterine RI while litter size did not (P > 0.1). Fetal heart rate increased from Day 30–50 and decreased to the time of parturition (P < 0.01) without differences among groups at any time point (P > 0.1). Uterine and umbilical blood flow differentially increased throughout mid- and late-pregnancy in breeds with large and small BW. These differences were affected by litter size on Days 40 and 50, and by maternal BW on Day 60. Conversely, during this same period, FHR did not vary among BW groups. Physiological variations should be considered when gestational ultrasonic examination is interpreted in different BW bitches.

Effects of arsenic exposure on D-serine metabolism in the hippocampus of offspring mice at different developmental stages.

The main purpose of this study was to verify the hypothesis that cognitive dysfunctions induced by arsenic exposure were related to the changes of D-serine metabolism in the hippocampus of offspring mice. Mother mice and their offsprings were exposed to 0, 15, 30 or 60mg/L sodium arsenite (NaAsO2) through drinking water from the first day of gestation until the end of lactation. D-serine levels in the hippocampus of mice of postnatal day (PND) 10, 20 and 40 were examined by high-performance liquid chromatography. Expressions of serine racemase (SR), D-amino acid oxidase (DAAO), alanine-serine-cysteine transporter-1 (asc-1) and subunits of N-methyl-D-aspartate receptors (NMDARs) in the hippocampus of mice were measured by Western blot and Real-time RT-PCR. Results showed that arsenic exposure significantly decreased D-serine levels of mice exposed to 60mg/L NaAsO2. Exposure to 60mg/L NaAsO2 could inhibit both mRNA and protein expression of SR, whereas increase in the protein expression of DAAO, only enhances the mRNA levels of DAAO of PND 20 mice. In addition, arsenic exposure could upregulate protein expression of asc-1. The mRNA and protein levels of NR1, NR2A and NR2B in the hippocampus of mice were down-regulated by arsenic. Findings from this study suggested that SR might play an important role in the reduction of D-serine levels caused by arsenic exposure, which might further influence the levels of NMDAR subunits especially on PND20, and then might disturb the function of NMDARs and cause the deficits of learning and memory ability of offspring mice.

Chronic lead exposure decreases the expression of Huntingtin-associated protein 1 (HAP1) through Repressor element-1 silencing transcription (REST)

Chronic lead (Pb) exposure has been shown to reduce the expression of some synaptic proteins which are involved in vesicular trafficking and affect presynaptic neurotransmitter release. However, the precise mechanisms by Pb impairs neurotransmitter release are still not well defined. In the current study, we aimed to elucidate the changes of Huntingtin-associated protein 1 (HAP1) in Pb exposed rats and PC12 cells models and its molecular mechanism. Repressor element-1 silencing transcription (REST) modulates the expression of genes containing the repressor element 1 (RE-1) cis-regulatory DNA sequence. HAP1 promoter region contains a RE-1 binding motif. We also observed whether Pb exposure regulated the HAP1 transcription level through influencing the expression of REST. Mother rats were exposed to 0.5 and 2 g/L Pb acetate (PbAc) in drinking water from the first day of gestation until postnatal 21 days, then the offspring rats were continued to drink PbAc for 1 year, while the control groups received drinking water. PC12 cells were divided into 3 groups: 0 μM, 1 μM and 100 μM PbAc. The results revealed that Pb levels in blood and brain of Pb exposed groups were significantly higher than that of the control group. The ability of learning and memory in Pb exposed rats was decreased. Pb exposure reduced the expression of HAP1 and increased the REST expression. Silencing REST could reverse the decreasing of HAP1 in Pb exposed PC12 cells. Our findings raise a possibility that the decreasing of HAP1 expression by Pb exposure may affect neurotransmitter release and results in impairments in spatial learning and memory ability.

Gestational diabetes reduced sertoli cells in 12 weeks age rat offsprings testis

IntroductionPrevious study has shown the adverse effects of type 1 and 2 diabetes mellitus on male reproductive system. This study was done to evaluate the effect of induced gestational diabetes on seminiferous tubule of 12 weeks age offspring rats. Methods10 Wistar rats' dams were randomly allocated to control and diabetic groups. Streptozotocin was used to induce diabetes in female rats. Dams in diabetic group received 40mg/kg/BW of streptozotocin at the first day of gestation and control group animals received an equivalent volume of normal saline by intraperitoneally. Six offspring of each group were randomly selected on day 84 postnatal. Five micrometer sections were taken from testes, stained with hematoxylin and eosin. Photographs of sections were taken using Olympus BX51 microscope and a digital camera DP12. Density and number of spermatogenesis cells, leydig cells, sertoli cells, seminiferous tubule diameter and Seminiferous epithelial height and dUTP end-labeling positive cells were evaluated in 50,000μm2 area of seminiferous tubules by Olysia Autobioreport software. ResultsSpermatogenesis and leydig cells in gestational diabetic offsprings non-significantly reduced in compare to controls. Sertoli cells significantly reduced in gestational diabetic offspring compared to controls. Seminiferous tubular diameter and seminiferous epithelial height non-significantly reduced in gestational diabetic offspring compared to controls. The apoptotic cells in diabetic group non-significantly increased in comparison with controls. The histopathological alterations were not seen in experimental group. DiscussionUncontrolled gestational diabetes significantly reduces the sertoli cells but non-significantly reduces the spermatogenic cells in the rat offsprings.

Use of trimethoprim-sulfamethoxazole during pregnancy and risk of spontaneous abortion: a nested case control study.

Data available on the fetal safety of trimethoprim-sulfamethoxazole (TMP-SMX) exposure during pregnancy remains scarce and inconclusive. A previous study assessing the link between TMP-SMX exposure during pregnancy and the risk of spontaneous abortion (SA) did not control for protopathic bias and indication bias. We conducted a nested control study (n=77 429 pregnancies including 7039 cases of SA and 70 390 controls) within the Quebec Pregnancy Cohort. For each case of SA, we selected 10 controls at the index date that were matched on gestational age and year of pregnancy. TMP-SMX exposure was defined as either having filled at least one prescription between the first day of gestation (1DG) and the index date, or as having filled a prescription before pregnancy but with a duration overlapping the 1DG (102 pregnancies exposed to TMP-SMX, including 25 cases of SA and 77 controls). Adjusting for potential confounders, TMP-SMX exposure was associated with an increased risk of SA (AOR 2.94, 95% C 1.89-4.57, 25 exposed cases). Similar results were found after controlling for indication bias and protopathic bias. Given that this drug is widely use in HIV patients to prevent opportunistic infections and malaria, there is an urgent need to identify potential data sources in Africa for analysis of early pregnancy exposure to TMP-SMX.

Lead exposure inhibits expression of SV2C through NRSF

Lead (Pb) exposure has been shown to affect presynaptic neurotransmitter release in the animal and cell models. The mechanism by which Pb exposure impairs neurotransmitter release remains unknown. In this study, we aimed to investigate the effect of Pb exposure on synaptic vesicle protein 2C (SV2C) and its molecular mechanism. SV2C promoter region contains a neuron-restrictive silencer element (NRSE) binding motif. Neuron-restrictive silencer factor (NRSF) is a transcription repressor that regulates gene expression by binding to NRSE. We also observed whether Pb exposure regulates the transcriptional level of SV2C by influencing the expression of NRSF. Pregnant female rats were exposed to 0, 0.5 and 2.0 g/L lead acetate (PbAc) via drinking water from the first day of gestation until postnatal week 3. Neuro-2a (N2a) cells were divided into 3 groups: 0 μM (control group), 1 μM and 100 μM PbAc. Our data revealed that the ability of learning and memory in Pb-exposed rats were decreased, Pb exposure decreased SV2C expression and increased NRSF expression in the rat hippocampus and N2a cell. Silencing NRSF can reverse the down-regulation of Pb exposure on SV2C. These results indicate that Pb exposure can inhibit the transcription level of SV2C by up regulating the expression of NRSF. Decreased expression of SV2C can affect neurotransmitter release and synaptic transmission, which affect synaptic plasticity and then result in impairment of learning and memory.

Chronic Exposure to Uranium from Gestation: Effects on Behavior and Neurogenesis in Adulthood.

Uranium exposure leads to cerebral dysfunction involving for instance biochemical, neurochemical and neurobehavioral effects. Most studies have focused on mechanisms in uranium-exposed adult animals. However, recent data on developing animals have shown that the developing brain is also sensitive to uranium. Models of uranium exposure during brain development highlight the need to improve our understanding of the effects of uranium. In a model in which uranium exposure began from the first day of gestation, we studied the neurobehavioral consequences as well as the progression of hippocampal neurogenesis in animals from dams exposed to uranium. Our results show that 2-month-old rats exposed to uranium from gestational day 1 displayed deficits in special memory and a prominent depressive-like phenotype. Cell proliferation was not disturbed in these animals, as shown by 5-bromo-2′deoxyuridine (BrdU)/neuronal specific nuclear protein (NeuN) immunostaining in the dentate gyrus. However, in some animals, the pyramidal cell layer was dispersed in the CA3 region. From our previous results with the same model, the hypothesis of alterations of neurogenesis at prior stages of development is worth considering, but is probably not the only one. Therefore, further investigations are needed to correlate cerebral dysfunction and its underlying mechanistic pathways.