Development Of Rat Offspring Research Articles

Maternal low-dose caffeine intake during the perinatal period promotes short- and long-term sex-dependent hormonal and behavior changes in the offspring.

Maternal caffeine crosses the placenta and mammary barriers, reaching the baby and, because his/her caffeine metabolism is immature, our hypothesis is that even a low caffeine intake (250 mg/day), lower than the dose limit recommended by the World Health Organization, can promote caffeine overexposure in the offspring, leading to short- and long-term changes. Pregnant Wistar rats received intragastric caffeine (CAF) (25 mg/Kg/day) or vehicle during the gestation and lactation periods. We evaluated morphometrical, metabolic, hormonal, and behavioral parameters of male and female offspring at different ages. Even a low caffeine intake promoted lower maternal body mass and adiposity, higher plasma cholesterol and lower plasma T3, without changes in plasma corticosterone. Female CAF offspring exhibited lower birth weight, body mass gain and food intake throughout life, and hyperinsulinemia at weaning, while male CAF offspring showed reduced food intake and lower plasma T3 at weaning. At puberty and adulthood, male CAF showed higher preference for palatable food, aversion to caffeine intake and higher locomotor activity, while female CAF only showed lower preference for high fat diet (HFD) and lower anxiety-like behavior. At adulthood, both male and female offspring showed higher plasma T3. Male CAF showed hypertestosteronemia, while female CAF showed hypoinsulinemia without effect on glucose tolerance. A low caffeine intake during the perinatal period affects rat's offspring development, promoting sex-dependent hormonal and behavior changes. Current data suggest the need to review caffeine recommendations during the perinatal period.

Evaluation of the effect of tartrazine on the offspring rats in an in vivo experimental model

AbstractTartrazine, an azo dye prevalent in pharmaceuticals and food items, was investigated for its impact on fetal development, specifically examining visceral and skeletal abnormalities in rat offspring exposed to daily oral doses throughout pregnancy. Fourteen pregnant rats were randomly assigned to control and tartrazine groups (seven animals each), with tartrazine administered via oral gavage at 7.5 mg/kg throughout gestation. Offspring were categorized by gender for histopathological and genetic analysis of visceral structures. Bone quality and fracture resistance assessments involved micro‐CT, Raman spectroscopy, and biomechanical testing. Results highlighted distinct internal organ tissue differences in the tartrazine group, notably increased hemorrhagic and inflammatory cell infiltration, degeneration, and vacuolization compared to controls. Gender‐specific alterations in mRNA levels of IL‐6, IL‐1β, TNF‐α, and TRPM2 genes (p < .001) were also noted. Moreover, tartrazine‐exposed groups exhibited reduced trabecular thickness, bone volume, and significant alterations in bone matrix composition and quality alongside significant decreases in fracture resistance (p < 0.05). This study concludes that intrauterine exposure to tartrazine can result in adverse impacts on organ and bone development in rat offspring.

Parental folic acid deficiency delays neurobehavioral development in rat offspring by inhibiting the differentiation of neural stem cells into neurons

Maternal folate status during pregnancy is associated with the neurodevelopment of offspring; however, study results on the association between paternal folate status and offspring neurodevelopment are inconsistent. This study aimed to explore whether parental folic acid deficiency affects the neurobehavioral development of offspring by affecting the differentiation of neural stem cells (NSCs) into neurons. In the present study, the offspring were divided into four groups: parental folic acid deficient group (D-D), maternal folic acid deficient and paternal folic acid normal group (D-N), maternal folic acid normal and paternal folic acid deficient group (N-D), and parental folic acid normal group (N-N). For in vivo study, neurobehavioral indexes, and neuron-specific nuclear protein (NeuN) and glial fibrillary acidic protein (GFAP) expression in the brain hippocampus and cerebral cortex of offspring were measured at different time points. For in vitro study, NSCs were cultured from the hippocampus and striatum, and neuronal and astrocytic differentiation were measured. The results demonstrated that parental folic acid deficiency decreased the brain folate level in offspring, delayed early sensory-motor reflex development, impaired spatial learning and memory ability in adolescence and adulthood, decreased differentiation of NSCs into neurons and increased differentiation of NSCs into astrocytes in vivo and in vitro. These impacts on the neurodevelopment of offspring were most pronounced in D-D group, followed by D-N group and N-D group. In conclusion, parental folic acid deficiency inhibits the neurobehavioral development of offspring, possibly by inhibiting the differentiation of NSCs into neurons.

Aspects of effect of novel compound exhibiting hypoglycemic activity on female rat reproduction processes

In experiments, in female rats, the novel substance dipiarone with hypoglycemic activity when administered intragastrically at doses of 0.5 mg/kg and 100 mg/kg from 6 to 16 days of gestation did not have a damaging effect on the processes of organo- and fetogenesis and did not contribute to the occurrence of deformities and abnormalities in the development of fetuses recorded in the antenatal and postnatal period of their development. Intragastric administration of dipiarone to rats at a dose of 100 mg/kg from 6 days of pregnancy until delivery showed that the formation of physical development of rat offspring in the postnatal period corresponds to the control parameters, while they had an increase in the rate of body weight gain, ahead of the time of formation of sensory-motor reflexes, activation of motor and emotional behavior.

Effect evaluation of supramolecular complex of ivermectin Aniverm-2.0% on postnatal development of rat offspring

The purpose of the research is to detect long-term effects of repeated oral administration of supramolecular complex of ivermectin Aniverm-2.0% on the postnatal development of rat offspring.Materials and methods. The studies were conducted on 16 white pregnant rats that were divided into two experimental and one control groups. The animals were kept under standard conditions of keeping and feeding. The supramolecular complex of ivermectin Aniverm-2.0% was administered to pregnant female rats (n = 6) of group 1 in the form of a suspension using an intragastric tube daily for 7 days at a dose of 15 mg/kg, and group 2 was given the substance of ivermectin (n = 5) at a dose of 8.25 mg/kg. The control female rats (n = 5) were administered 1 mL of distilled water during the experiment. The experimental pregnant females were left until delivery, and then, the development of their offspring was monitored for 45 days. After rat pups were born, the following were recorded: pregnancy duration, litter size, dynamics of weight gain in the rat pups for 21 days, postnatal death during the first 30 days, the ratio of males and females in the litter, periods of eye opening, incisor eruption, detachment of the auricle, appearance of hair coat, descent of testicles, and opening of the vagina. Then we assessed the maturation rate of sensory-motor reflexes in the offspring obtained from the experimental and control groups, the emotional motor behavior and ability for fine coordination of movements in the offspring, and conducted the open field-2 test on day 45 after birth.Results and discussion. No negative effect was detected for supramolecular complex of ivermectin Aniverm-2.0% on the parameters of physiological development of the offspring of the experimental rats within 45 days after birth. The dynamics of their mass, developmental parameters, and formation of motor reflexes during the feeding period remained within the normal values. Developmental indicators of sensory motor reflexes in the control and experimental rat pups had no statistically significant differences.

Maternal Exposure to Acephate Caused Nephrotoxicity in Adult Offspring Rats Mediated by Excessive Autophagy Activation, Oxidative Stress Induction, and Altered Epithelial Sodium Channel and Na+/K+-ATPase Gene Expression

This study examined how maternal exposure to acephate-an organophosphate-based insecticide-affected the renal development in rat offspring during adulthood. Virgin female Wistar rats were randomly allocated to three groups: group 1 (control) received sterile water; groups 2 and 3 were intragastrically exposed to low (14 mg/kg) and high (28 mg/kg) doses of acephate from day 6 of pregnancy until delivery, respectively. Further, the offspring of the adult female rats were euthanized in postnatal week 8. Compared with the controls, the adult rat offspring with exposure to low and high doses of acephate exhibited elevated plasma creatinine and blood urea nitrogen levels. Additionally, immunofluorescence analysis revealed the upregulation of autophagic marker genes (Beclin-1 and LC-3) in the acephate-treated rat offspring, thereby suggesting the induction of an autophagic mechanism. Notably, the increased malondialdehyde level, decreased glutathione level, and decreased superoxide dismutase and catalase activities confirmed the ability of acephate to induce oxidative stress and apoptosis in the kidneys of the rat offspring. This may explain the renal histopathological injury detected using hematoxylin and eosin staining. Furthermore, a reverse transcription polymerase chain reaction revealed that the mRNA expression levels of the Na+/K+-ATPase and the epithelial sodium channel (ENaC) genes were significantly higher in the kidney of female offspring than that of controls owing to acephate toxicity. However, there was no significant effect of acephate on the expression of NHE3 in the treatment group compared with the control group. Overall, the present findings suggest that oxidative stress caused by prenatal exposure to acephate causes nephrotoxicity and histopathological alterations in adult rat offspring, likely by actions on renal ENaC and Na+/K+-ATPase genes as well as the autophagic markers Beclin-1 and LC-3.

Peculiarities of antenatal development of rat offspring against aqueous extract of centella asiatica

Purpose: study of the characteristics of the antenatal development of the offspring of rats treated with an aqueous extract of centella asiatica as an additional load.Materials and methods. The experiment was carried out on 126 (90 females and 36 males) white outbred rats, which were divided equally into 9 groups and, in accordance with the group affiliation, as well as the established period, received daily intragastrically an aqueous plant extract of Centella asiatica at a dose of 30 mg/100 g of body weight animal, 1 ml: group 1 - intact animals (control); group 2 - females and males received an aqueous extract of Centella asiatica for 30 days before pregnancy; group 3 - an aqueous extract of Centella Asiatica for 30 days received females before pregnancy, and males - distilled water; group 4 - an aqueous extract of Centella asiatica for 30 days received males before mating, females - distilled water before mating; group 5 - an aqueous extract of Centella asiatica within 30 days before mating and up to 13 days of pregnancy, females received, and males - distilled water; group 6 - an aqueous extract of Centella asiatica within 30 days before mating and from 14 to 20 days of pregnancy, females received, and males - distilled water; group 7 - an aqueous extract of Centella asiatica from 1 to 13 days of pregnancy received females, males - distilled water; group 8 - water extract of centella asiatica from 14 to 20 days of pregnancy received females, males - distilled water; Group 9 - an aqueous extract of Centella asiatica within 30 days before mating and within 20 days of pregnancy, females received, and males - distilled water. Animals of the control group received daily intragastric distilled water, 1 ml. Standard methods were used to obtain dated gestation females. Accounting for the results of the experiment was carried out on the 20th day of pregnancy of rats by euthanasia of animals, the number of live, dead, reserved fetuses was counted, marking the implantation sites, the anatomical structure of the fetuses, their weight and size were evaluated; embryonic (pre- and post-implantation) death of fetuses was considered, anomalies of external and internal development were revealed.Results. Additional intragastric loading of male and female rats with an aqueous extract of centella asiatica contributed to an increase in the average number of fetuses in a litter, corpus luteum per 1 female, implantation sites, a decrease in pre-implantation death of embryos and overall mortality, as well as an increase in the weight of fetuses and their cranio-caudal sizes, moreover, the duration of the load was expressed in a more positive trend. The load for 50 days was reflected in the highest rates among the studied groups. With regard to the presence of anomalies in the external and internal development of the fetus, an extremely low percentage of individuals with defects should be noted, both in the control and experimental groups.

Effects of maternal iodine nutritional status on neurodevelopmental and cognitive function of rat offspring.

This study aimed to explore the effect of maternal iodine status on the brain development of offspring in rats. Since in human studies, the interference of environmental factors and other nutrients cannot be removed. A total of 48 female Wistar rats were randomly divided into four groups: low iodine (LI), normal iodine (NI), 10-fold high iodine (10HI), and 50-fold high iodine (50HI). The rats were killed on the 15th day of pregnancy and lactation after collecting 24-h urine. The iodine concentration in 24-h urine, blood, and placenta of pregnant rats, and 24-h urine, milk, blood, and mammary glands of lactating rats was determined by inductively coupled plasma mass spectrometry. The thyroid hormone of pregnant and lactating rats was detected by chemiluminescence. The offspring were subjected to the Morris water maze on the 10th day after birth. Serum was collected to detect the thyroid hormone of offspring. The protein expression of neuroendocrine-specific protein (NSP)-A and brain-derived neurotrophic factor (BDNF) in the offspring brain were studied. Iodine storage in the placenta during pregnancy and mammary glands during lactation was positively correlated with iodine intake, and iodine storage in the placenta and mammary glands in the 50HI group was significantly higher than that in the NI group (P = 0.045 and P = 0.040). Compared with the NI group, the offspring thyroid-stimulating hormone (TSH) level was significantly higher in the 10HI group (P = 0.046), and the FT4 level was significantly lower in the 50HI group (P = 0.032). The Morris water maze showed that LI and 50HI groups required longer time and distance to find the platform than the NI group (P < 0.001). The platform crossing numbers in the LI and 50HI groups decreased significantly (P < 0.001). The expression of NSP-A in offspring brain was lower in the 10HI and 50HI groups than in the NI group (P = 0.026 and P = 0,008). BDNF expression levels were significantly lower in the LI, 10HI, and 50HI groups than in the NI group (P < 0.001). Maternal iodine intake affects iodine storage in the placenta and lactating mammary gland, which in turn affects thyroid function and BDNF and NSP-A expression in the offspring.

Effects of Pregnant Fatigue on the Development of Offspring in Rats.

To explore the correlation between pregnant fatigue and intrauterine physical and neural development of offspring in rats. Sprague-Dawley pregnant rats were randomly divided into a normal control group, a mild fatigue group (stand in water for 6 hours/day), and a severe fatigue group (stand in water for 15h/day). The levels of lactic acid, 5-Hydroxytryptamine and Interleukin-6 in cardiac serum of rats were used to evaluate the fatigue. The expression of S100β in the telencephalon, Insulin-like growth factor-1 (IGF-1) in the liver and Cyclooxygenage-2 (COX-2) in the small intestine tissues of fetal rats were examined. Frozen sections were taken from the telencephalon of rat pups to observe morphological changes in the hippocampal primordium. Pregnant fatigue led to a decrease in food intake (F = 37.586, p = 0.000) and water intake (F = 23.608, p = 0.000) in rats. The IGF-1 mRNA expression of fetal rats in the severe fatigue group was lower than that in the control group (p = 0.0003). The expression of S100β mRNA (p = 0.000) and COX-2 mRNA (p = 0.0002) of fetal rats were higher in the severe fatigue group than in the control group. HE staining of the telencephalon of fetal rats in the pregnant fatigue group revealed sparse and irregular cell arrangement and increased gaps in the hippocampal primordial site. Pregnant fatigue rats had both physical fatigue and mental fatigue. Fatigue during pregnancy affects physical development and neurodevelopment of offspring. Further research should elucidate the mechanisms of pregnant fatigue and its effects on offspring.

Impacts of a perinatal exposure to manganese coupled with maternal stress in rats: Maternal somatic measures and the postnatal growth and development of rat offspring

Psychological stress experienced by the mother during pregnancy has been associated with emotional and cognitive disorders in children such as depression and anxiety. Socioeconomically disadvantaged populations are vulnerable to adverse life experiences and can also be disproportionally exposed to environmental contaminants. To better understand the neurodevelopmental impacts of an environmental toxicant coupled with elevated psychological stress, we exposed pregnant rats to a series of perinatal stressors. Manganese (Mn), a neurotoxicant at excessive concentrations was delivered through drinking water (0, 2, or 4 mg/mL) from gestational day (GD) 7 to postnatal day (PND) 22. A variable stress paradigm was applied to half of the animals from GD13 to PND9. Measurements of somatic development and behavior were examined in the offspring at different developmental stages. No evidence of overt maternal toxicity was observed although the 4 mg/mL Mn-exposed dams gained less body weight during gestation compared to the other dams. Stress also reduced gestational maternal weight gain. Daily fluid consumption normalized for body weight was decreased in the Mn-exposed dams in a dose-dependent manner but was not altered by the stress paradigm. Maternal stress and/or Mn exposure did not affect litter size or viability, but pup weight was significantly reduced in the 4 mg/mL Mn-exposed groups on PNDs 9 through 34 when compared to the other offspring groups. The efficacy of the manipulations to increase maternal stress levels was determined using serum corticosterone as a biomarker. The baseline concentration was established prior to treatment (GD7) and levels were low and similar in all treatment groups. Corticosterone levels were elevated in the perinatal-stress groups compared to the no-stress groups, regardless of Mn exposure, on subsequent time points (GD16, PND9), but were only significantly different on GD16. An analysis of tissue concentrations revealed Mn was elevated similarly in the brain and blood of offspring at PND2 and at PND22 in a significant dose-dependent pattern. Dams also showed a dose-dependent increase in Mn concentrations in the brain and blood; the addition of stress increased the Mn concentrations in the maternal blood but not the brain. Perinatal stress did not alter the effects of Mn on the maternal or offspring somatic endpoints described here.

Lack of effects on female fertility or pre- and postnatal development of offspring in rats after exposure to AS03-adjuvanted recombinant plant-derived virus-like particle vaccine candidate for COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection resulting in the coronavirus disease 2019 (COVID-19) has afflicted tens of millions of people in a worldwide pandemic. A recently developed recombinant Plant-Derived Virus-Like Particle Vaccine candidate for COVID-19 (CoVLP) formulated with AS03 has been shown to be well-tolerated and highly immunogenic in healthy adults. Since the target population for the vaccine includes women of childbearing potential, the objective of the study was to evaluate any untoward prenatal and postnatal effects of AS03-adjuvanted CoVLP administered intramuscularly to Sprague-Dawley female rats before cohabitation for mating (22 and 8 days prior) and during gestation (Gestation Days [GD] 6 and 19). The embryo-fetal development (EFD) cohort was subjected to cesarean on GD 21 and the pre/post-natal (PPN) cohort was allowed to naturally deliver. Effects of AS03-adjuvanted CoVLP was evaluated on pregnant rats, embryo-fetal development (EFD), during parturition, lactation and the development of the F1 offspring up to weaning Vaccination with AS03-adjuvanted CoVLP induced an antibody response in F0 females and anti-SARS-CoV-2 spike-specific maternal antibodies were detected in the offspring at the end of the gestation and lactation periods. Overall, there was no evidence of untoward effects of AS03-adjuvanted CoVLP on the fertility or reproductive performance of the vaccinated F0 females. There was no evidence of untoward effects on embryo-fetal development (including teratogenicity), or early (pre-weaning) development of the F1 offspring. These results support the acceptable safety profile of the AS03-adjuvanted CoVLP vaccine for administration to women of childbearing potential.

Effects of Prenatal Exposure to Perfluorononanoic Acid on Neurobehavioral Development in Rat Offspring

BACKGROUND AND AIM: Perfluorononanoic Acid (PFNA), a kind of fluorinated aliphatic molecules, had been extensively used in industrial applications as a surface protectant and known to accumulate in humans and wildlife. Although PFNA had been adversely associated with the growth and development of wild-type mice, much less is known about the impact of short-term exposure to PFNA during gestation on neurobehavioral development in rat offspring. The purpose of this study was to investigate the effects of PFNA on the physical and neurobehavioral development in sprague-dawley rat offspring. METHODS: Dams were dosed daily via oral gavage during gestation days 1-19 with control, 0.02, 0.2, 1.0, and 5.0 mg/kg of PFNA. During postnatal day (PND) 1-21, a series of developmental test battery were conducted, including body weight, maturational milestones (pinnae unfolding, incisor eruption, hair growth and eye opening) and neurobehavioral reflex (surface righting reflex, negative geotaxis, and cliff avoidance tests). Morris water maze tests were performed to study the learning and memory ability of the rat offspring on PND 28. RESULTS:PFNA exposure during gestation resulted in lower weight (≥1.0 mg/kg), later eye opening and worse performance in negative geotaxis (5.0 mg/kg), but no associations were observed between PFNA exposure and other maturational milestones or neurobehavioral reflex. Further, morris water maze tests indicated damaged spatial learning and memory ability of offspring (≥0.2 mg/kg). CONCLUSIONS:Our study reveals that PFNA exposure during gestation produce multiple adverse effects on neuro-development in rat, research is needed to examine the potential mechanisms linked to the adverse effects of PFNA. KEYWORDS: perfluorononanoic acid, neurobehavioral development, rat offspring, prenatal exposure

Effects of sevoflurane exposure during different stages of pregnancy on the brain development of rat offspring

ObjectiveThis study explored the effects of sevoflurane exposure during different stages of pregnancy on the brain development of offspring.MethodsThirty-six pregnant SD rats were randomly divided into 4 groups: control, sevoflurane exposure in early (S1) pregnancy, sevoflurane exposure in middle (S2) pregnancy, and sevoflurane exposure in late (S3) pregnancy. After natural birth, the learning and memory capacity of offspring rats was analyzed using the Morris water maze experiment. The hippocampi of offspring rats were collected. The levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in the hippocampus were measured by ELISA. Additionally, the Nissl bodies in the hippocampus were analyzed using Nissl staining. Immunohistochemistry was used to examine the expression of BDNF and CPEB2 in the hippocampus of offspring. Proteins related to the NR4A1/NF-κB pathway were analyzed using western blotting.ResultsThe memory and learning capacity of offspring rats was significantly reduced in the S1 and S2 groups compared to the control group (p < 0.05), while there was no obvious difference between the control and S3 groups (p > 0.05). The level of IL-1β was significantly increased (p < 0.05) in the S1 group compared with the control group. Sevoflurane anesthesia received in early and middle pregnancy could significantly affect the formation of Nissl bodies in the hippocampi of offspring rats. In addition, the expression of BDNF and CPEB2 in the hippocampi of offspring rats was greatly decreased in the S1 group compared with the control group (p < 0.05). The expression of NR4A1 in the hippocampi of rat offspring was significantly decreased in the S1 and S2 groups compared with the control group (p < 0.05). The expression of proteins related to the NF-κB pathway was increased in the S1 group compared to the control group (p < 0.05).ConclusionsThe neurotoxic effect of maternal sevoflurane anesthesia on the brain development of offspring is higher when the exposure occurs in early pregnancy than in late pregnancy, and its mechanism might involve the NR4A1/NF-κB pathway to increase the secretion of inflammatory cytokines.

Lack of effects on female fertility and prenatal and postnatal offspring development in rats with BNT162b2, a mRNA-based COVID-19 vaccine

BNT162b2 is a vaccine developed to prevent coronavirus disease 2019 (COVID-19). BNT162b2 is a lipid nanoparticle formulated nucleoside-modified messenger RNA (mRNA) encoding the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein locked in its prefusion conformation. A developmental and reproductive toxicity study was conducted in rats according to international regulatory guidelines. The full human BNT162b2 dose of 30 μg mRNA/dose (>300 times the human dose on a mg/kg basis) was administered intramuscularly to 44 female rats 21 and 14 days prior to mating and on gestation days 9 and 20. Half of the rats were subject to cesarean section and full fetal examination at the end of gestation, and the other half were allowed to deliver and were monitored to the end of lactation. A robust neutralizing antibody response was confirmed prior to mating and at the end of gestation and lactation. The presence of neutralizing antibodies was also confirmed in fetuses and offspring. Nonadverse effects, related to the local injection site reaction, were noted in dams as expected from other animal studies and consistent with observations in humans. There were no effects of BNT162b2 on female mating performance, fertility, or any ovarian or uterine parameters nor on embryo-fetal or postnatal survival, growth, physical development or neurofunctional development in the offspring through the end of lactation. Together with the safety profile in nonpregnant people, this ICH-compliant nonclinical safety data supports study of BNT162b2 in women of childbearing potential and pregnant and lactating women.

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.

Prenatal exposure to bisphenols affects pregnancy outcomes and offspring development in rats

The objective of this study was to evaluate the effects of gestational exposure to low doses of bisphenol A (BPA), bisphenol S (BPS), and bisphenol F (BPF) on pregnancy outcomes and offspring development. Pregnant Sprague-Dawley rats were orally dosed with vehicle, 5 μg/kg body weight (BW)/day of BPA, BPS and BPF, or 1 μg/kg BW/day of BPF on gestational days 6–21. Pregnancy and gestational outcomes, including number of abortions and stillbirths, were monitored. Male and female offspring were subjected to morphometry at birth, followed by pre- and post-weaning body weights, post-weaning food and water intakes, and adult organ weights. Ovarian follicular counts were also obtained from adult female offspring. We observed spontaneous abortions in over 80% of dams exposed to 5 μg/kg of BPF. BPA exposure increased Graafian follicles in female offspring, while BPS and BPF exposure decreased the number of corpora lutea, suggesting reduced ovulation rates. Moreover, BPA exposure increased male kidney and prostate gland weights, BPF decreased epididymal adipose tissue weights, and BPS had modest effects on male abdominal adipose tissue weights. Prenatal BPS exposure reduced anogenital distance (AGD) in male offspring, suggesting possible feminization, whereas both BPS and BPA induced oxidative stress in the testes. These results indicate that prenatal exposure to BPF affects pregnancy outcomes, BPS alters male AGD, and all three bisphenols alter certain organ weights in male offspring and ovarian function in female offspring. Altogether, it appears that prenatal exposure to BPA or its analogues can induce reproductive toxicity even at low doses.

Thyroid hormones, Sertoli cell proliferation and differentiation in progenies from carbamazepine-treated rat dams during pregnancy and lactation.

Carbamazepine (CBZ) is used in the control of seizure and affective disorders, causing hypothyroidism. Thyroid hormones regulate the Sertoli cell proliferation and differentiation. Clinical aspects must be considered since epileptic fertile women need to continuously use CBZ during pregnancy and lactation. This study aimed to evaluate the effects of CBZ on testis development of rat offspring from dams treated during pregnancy/lactation. Rat dams received CBZ (20mgkg-1 day-1 ) or vehicle by intra-peritoneal route during gestation and lactation. Progenies were euthanised at 4, 14, 41, 63 and 93-days post-partum (dpp) for the evaluation of T3, T4 and TSH plasma total levels. Testicular cross sections were submitted to anti-Ki67, anti-PCNA, anti-p27kip1 and anti-transferrin immunolabelling for the evaluation of Sertoli cells. There was a significant reduction in p27kip1 -positive Sertoli cell numerical densities and an increase in TSH level at 14 dpp. CBZ exposure affected the volume density of transferrin-positive immunolabelling at 63 dpp. These results suggest that CBZ may cause a dysregulation of the controller system of thyroid hormones homeostasis leading to an increase in the proliferation rate at the neonatal phase and a differentiation delay of the Sertoli cell, culminating in an altered function at late puberty. The occurrence of hypothyroidism cannot be completely discarded.

Buttermilk: an important source of lipid soluble forms of choline that influences the immune system development in Sprague-Dawley rat offspring.

To determine the effect of feeding buttermilk-derived choline metabolites on the immune system development in Sprague-Dawley rat pups. Sprague-Dawley dams were randomized to one of the three diets containing 1.7g/kg choline: 1-Control (100% free choline (FC)), 2-Buttermilk (BM, 37% phosphatidylcholine (PC), 34% sphingomyelin (SM), 17% glycerophosphocholine (GPC), 7% FC, 5% phosphocholine), and 3-Placebo (PB, 50% PC, 25% FC, 25% GPC) until the end of the lactation period. At weaning, pups continued on the same diet as their mom. Cell phenotypes and cytokine production by mitogen-stimulated splenocytes isolated from 3- and 10-week-old pups were measured. At 3weeks, BM-pups had a higher proportion of cytotoxic T cells (CTL; CD3 + CD8 +) while both BM- and PB-pups had an increased proportion of cells expressing CD28 + , CD86 + and CD27 + (all p > 0.05). Following ConA stimulation, splenocytes from BM- and PB-pups produced more TNF-α and IFN-γ and after LPS stimulation produced more IL-10 and TNF-α (all p > 0.05). Starting at week 6 of age, BM-pups had a higher body weight. At 10weeks, both the BM- and PB-pups had a higher proportion of CTL expressing CD27 + . After ConA stimulation, splenocytes from BM- and PB-pups produced more IL-2, IFN-γ and IL-6 and more IL-10 after LPS stimulation (all p > 0.05). The proportion of lipid soluble forms of choline in the diet during lactation and weaning periods influence the immune system development in rat offspring.

Prenatal sevoflurane exposure causes abnormal development of the entorhinal cortex in rat offspring.

As a gamma-aminobutyric acid type A receptor agonist sevoflurane is a common general anesthetic used in anesthesia and affects the neural development in offspring. We hypothesized that sevoflurane could regulate interneurons via the neuregulin-1-epidermal growth factor receptor-4 (NRG1-ErbB4) pathway in the entorhinal cortex (ECT) of the middle pregnancy. Six female rats in middle pregnancy (14.5 days of pregnancy) were randomly and equally divided into sevoflurane (SeV) and control groups. The rats in the SeV group were exposed to 4% sevoflurane for 3 hours. The expression levels of NRG1 and ErbB4, parvalbumin (PV) and glutamic acid decarboxylase (GAD67), and N-methyl-D-aspartate receptor subunit 2A (NR2A) and subunit 2B (NR2B) in offspring were examined through immunohistochemistry. The pyramidal neurons in the ECT were examined via Golgi staining. The levels of NRG1 and ErbB4 were significantly decreased (P < 0.01) and the levels of PV and GAD67 (interneurons) were found to be decreased in the SeV group (P < 0.01). The level of NR2B was found to be increased while the level of NR2A being decreased in the SeV group (P < 0.01). The development of pyramidal neurons was abnormal in the SeV group (P < 0.05). Conclusively, prenatal sevoflurane exposure could lead to the disturbance of the interneurons by activating the NRG1-ErbB4 pathway and subsequently result in abnormal development of pyramidal neurons in middle pregnancy. Prenatal sevoflurane exposure in middle pregnancy could be potentially harmful to the neural development of rat offspring. This study may reveal a novel pathway in the influence mechanism of sevoflurane on rat offspring.

The effects of prenatal and postnatal exposure to electromagnetic field on rat ovarian tissue.

Exposure to an electromagnetic field (EMF) can have adverse effects on many organs and tissues, including the reproductive system. This study aimed to investigate the effects of EMF exposure during prenatal and postnatal periods on ovarian development in rat offspring. In this study, rat pups born from eight pregnant rats were used. EMF exposure was initiated on the first day of pregnancy and continued until the 42nd postnatal day. The blood and ovarian tissue samples of female offspring in sham and EMF groups were collected when they reached the age of 42 days. Follicle-stimulating hormone levels were significantly higher in the EMF group than in the sham group. Estradiol levels were significantly lower in the EMF group than in the sham group. Tissue-inducible nitric oxide synthase (iNOS) levels and expression were significantly greater in the EMF group than in the sham group. In the EMF group, congestion, bleeding areas, and degeneration of follicle structures were observed in ovarian tissue. The findings suggest that exposure to 50-Hz, 3-mT EMF used in this study during prenatal and postnatal periods may lead to impaired ovarian structure and function in female offspring. EMF may affect ovarian physiology by increasing iNOS levels and may lead to fertility disorders.