Maternal viral mimetic administration at the beginning of fetal hypothalamic nuclei development accelerates puberty in female rat offspring

2018 ◽  
Vol 96 (5) ◽  
pp. 506-514 ◽  
Author(s):  
Pinar Cakan ◽  
Sedat Yildiz ◽  
Tuba Ozgocer ◽  
Azibe Yildiz ◽  
Nigar Vardi
Keyword(s):  
Viral Infection ◽  
Body Mass ◽  
Time Window ◽  
Critical Time ◽  
Female Offspring ◽  
Poly I:C ◽  
Female Rat ◽  
Pregnant Rats ◽  
Rat Offspring ◽  
Polycytidylic Acid

This study aimed to investigate the effects of maternal viral infection during a critical time window of fetal hypothalamic development on timing of puberty in the female offspring. For that purpose, a viral mimetic (i.e., synthetic double-strand RNA, namely, polyinosinic–polycytidylic acid, poly (I:C)) or saline was injected (i.p.) to the pregnant rats during the beginning (day 12 of pregnancy, n = 5 for each group) or at the end of this time window (day 14 of pregnancy, n = 5 for each group). Four study groups were formed from the female pups (n = 9–10 pups/group). Following weaning of pups, vaginal opening and vaginal smearing was studied daily until 2 sequential estrous cycles were observed. During the second diestrus phase, blood samples were taken for progesterone, leptin, corticosterone, follicle-stimulating hormone, and luteinizing hormone. Maternal poly (I:C) injection on day 12 of pregnancy increased body mass and reduced the time to puberty in the female offspring. Neither poly (I:C) nor timing of injection affected other parameters studied (p > 0.05). It has been shown for the first time that maternal viral infection during the beginning of fetal hypothalamic development might hasten puberty by increasing body mass in rat offspring.

Maternal quercetin intake during lactation attenuates renal inflammation and modulates autophagy flux in high-fructose-diet-fed female rat offspring exposed to maternal malnutrition

2019 ◽  
Vol 10 (8) ◽  
pp. 5018-5031 ◽  
Author(s):  
Shin Sato ◽  
Toshio Norikura ◽  
Yuuka Mukai
Keyword(s):  
Female Offspring ◽  
Female Rat ◽  
Autophagy Flux ◽  
Maternal Malnutrition ◽  
High Fructose Diet ◽  
Rat Offspring ◽  
Low Protein ◽  
High Fructose ◽  
Protein Diets

Quercetin intake during lactation causes long-term alterations in inflammation and autophagy flux in the kidneys of high-fructose-diet-fed adult female offspring exposed to maternal normal- or low-protein diets.

Prenatal Dexamethasone Exposure Induced Alterations in Neurobehavior and Hippocampal Glutamatergic System Balance in Female Rat Offspring

2019 ◽  
Vol 171 (2) ◽  
pp. 369-384 ◽  
Author(s):  
Songqiang Huang ◽  
Wanting Dong ◽  
Zhexiao Jiao ◽  
Jie Liu ◽  
Ke Li ◽  
...  
Keyword(s):  
Glucocorticoid Receptors ◽  
Female Offspring ◽  
Abnormal Behavior ◽  
Control Group ◽  
Female Rat ◽  
Glutamatergic System ◽  
Fetal Origins ◽  
Histone Deacetylase 2 ◽  
Rat Offspring

Abstract Epidemiological investigations have suggested that periodic use of dexamethasone during pregnancy is a risk factor for abnormal behavior in offspring, but the potential mechanism remains unclear. In this study, we investigated the changes in the glutamatergic system and neurobehavior in female offspring with prenatal dexamethasone exposure (PDE) to explore intrauterine programing mechanisms. Compared with the control group, rat offspring with PDE exhibited spatial memory deficits and anxiety-like behavior. The expression of hippocampal glucocorticoid receptors (GR) and histone deacetylase 2 (HDAC2) increased, whereas histone H3 lysine 14 acetylation (H3K14ac) of brain-derived neurotrophic factor (BDNF) exon IV (BDNF IV) and expression of BDNF decreased. The glutamatergic system also changed. We further observed that changes in the fetal hippocampus were consistent with those in adult offspring. In vitro, the administration of 0.5 μM dexamethasone to the H19-7 fetal hippocampal neuron cells directly led to a cascade of changes in the GR/HDAC2/BDNF pathway, whereas the GR antagonist RU486 and the HDAC2 inhibitor romidepsin (Rom) reversed changes caused by dexamethasone to the H3K14ac level of BDNF IV and to the expression of BDNF. The increase in HDAC2 can be reversed by RU486, and the changes in the glutamatergic system can be partially reversed after supplementation with BDNF. It is suggested that PDE increases the expression of HDAC2 by activating GR, reducing the H3K14ac level of BDNF IV, inducing alterations in neurobehavior and hippocampal glutamatergic system balance. The findings suggest that BDNF supplementation and glutamatergic system improvement are potential therapeutic targets for the fetal origins of abnormal neurobehavior.

Abnormal glucose homeostasis in adult female rat offspring after intrauterine ethanol exposure

2007 ◽  
Vol 292 (5) ◽  
pp. R1926-R1933 ◽  
Author(s):  
Xing-Hai Yao ◽  
B. L. Grégoire Nyomba
Keyword(s):  
Skeletal Muscle ◽  
Glucose Tolerance ◽  
Adult Female ◽  
Insulin Signaling ◽  
Glucose Transporter ◽  
Female Offspring ◽  
Female Rat ◽  
Glucose Transporter 4 ◽  
Insulin Resistant ◽  
Rat Offspring

Adverse events during pregnancy, including prenatal ethanol (EtOH) exposure, are associated with insulin-resistant diabetes in male rat offspring, but it is unclear whether this is true for female offspring. We investigated whether prenatal EtOH exposure alters glucose metabolism in adult female rat offspring and whether this is associated with reduced in vivo insulin signaling in skeletal muscle. Female Sprague-Dawley rats were given EtOH, 4 g·kg−1·day−1 by gavage throughout pregnancy. Glucose tolerance test and hyperinsulinemic euglycemic clamp were performed, and insulin signaling was investigated in skeletal muscle, in adult female offspring. We gave insulin intravenously to these rats and determined the association of glucose transporter-4 with plasma membranes, as well as the phosphorylation of phosphoinositide-dependent protein kinase-1 (PDK1), Akt, and PKCζ. Although EtOH offspring had normal birth weight, they were overweight as adults and had fasting hyperglycemia, hyperinsulinemia, and reduced insulin-stimulated glucose uptake. After insulin treatment, EtOH-exposed rats had decreased membrane glucose transporter-4, PDK1, Akt, and PKCζ in the gastrocnemius muscle, compared with control rats. Insulin stimulation of PDK1, Akt, and PKCζ phosphorylation was also reduced. In addition, the expression of the protein tribbles-3 and the phosphatase enzyme activity of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), which prevent Akt activation, were increased in muscle from EtOH-exposed rats. Female rat offspring exposed to EtOH in utero develop insulin-resistant diabetes in association with excessive PTEN and tribbles-3 signaling downstream of the phosphatidylinositol 3-kinase pathway in skeletal muscle, which may be a mechanism for the abnormal glucose tolerance.

scholarly journals PSV-18 Program Chair Poster Pick: Poly(I:C) dose response and its effects on piglet sickness behaviors

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 218-218
Author(s):  
Haley E Rymut ◽  
Courtni R Bolt ◽  
Megan P Corbett ◽  
Laurie A Rund ◽  
Rodney W Johnson ◽  
...  
Keyword(s):  
Viral Infection ◽  
Viral Infections ◽  
Sickness Behavior ◽  
Activity Level ◽  
Poly I:C ◽  
Activity Levels ◽  
Post Injection ◽  
Mixed Effect ◽  
Polycytidylic Acid ◽  
Sickness Behaviors

Abstract The synthetic polyinosinic-polycytidylic acid Poly(I:C) is commonly used to mimic viral infection in rodents. A Poly(I:C) injection activates inflammatory receptors that recognize viral patterns. This immune-stimulating agent can be used to understand the effects of viral infection on pork production. The objective of this study was to compare the effects of multiple Poly(I:C) doses on sickness behaviors across time. Female and male pigs from the University of Illinois Swine herd, averaging 24.5 kg, were injected with 1 mg/kg or 0.5 mg/kg of Poly(I:C), or comparable volume of Saline at approximately 60 days of age. Post injection, sickness behaviors and activity levels were measured in 15-minute intervals by a trained experimenter for three hours. Observed sickness behaviors included vomiting, diarrhea, or shivering. The activity levels were scored 1 through 8 with lower levels indicating pigs running, medium levels indicating walking, and higher levels indicating laying behaviors. The binary sickness behavior and discrete activity levels from 130 observations from 10 pigs evenly distributed across sexes were analyzed using generalized mixed effect models. The model included the effects of Poly(I:C) dose, hour, sex, and interactions, and a repeated structure within pig. The administration of Poly(I:C) had a significant effect on activity level within one-hour post-injection, and Poly(I:C)-treated pigs had lower activity levels than the Saline group. The Poly(I:C) effect had a lower significance in males (P < 0.001) than females (P < 0.004). The Poly(I:C) treatment also had a significant effect on the probability of sickness behavior (P < 0.005). The probability of sickness behavior was 0.03, 0.18, and 0.23 for pigs treated with Saline, 0.5, and 1.0 mg/kg of Poly(I:C), respectively. Our results suggest that Poly(I:C) could be an effective agent in studying sickness response to viral infections in pigs. This study is supported by USDA NIFA AFRI, grant number 2018-67015-27413.

scholarly journals High Folic Acid Intake during Pregnancy Lowers Body Weight and Reduces Femoral Area and Strength in Female Rat Offspring

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Pedro S. P. Huot ◽  
David W. Dodington ◽  
Rebecca C. Mollard ◽  
Sandra A. Reza-López ◽  
Diana Sánchez-Hernández ◽  
...  
Keyword(s):  
Body Weight ◽  
Folic Acid ◽  
Maternal Diet ◽  
Control Diet ◽  
Peak Load ◽  
Lumbar Vertebrae ◽  
Lumbar Vertebra ◽  
Female Rat ◽  
Pregnant Rats ◽  
Rat Offspring

Rats fed gestational diets high in multivitamin or folate produce offspring of altered phenotypes. We hypothesized that female rat offspring born to dams fed a gestational diet high in folic acid (HFol) have compromised bone health and that feeding the offspring the same HFol diet attenuates these effects. Pregnant rats were fed diets with either recommended folic acid (RFol) or 10-fold higher folic acid (HFol) amounts. Female offspring were weaned to either the RFol or HFol diet for 17 weeks. HFol maternal diet resulted in lower offspring body weights (6%,P=0.03) and, after adjusting for body weight and femoral length, smaller femoral area (2%,P=0.03), compared to control diet. After adjustments, HFol pup diet resulted in lower mineral content (7%,P=0.01) and density (4%,P=0.002) of lumbar vertebra 4 without differences in strength. An interaction between folate content of the dam and pup diets revealed that a mismatch resulted in lower femoral peak load strength (P=0.01) and stiffness (P=0.002). However, the match in folate content failed to prevent lower weight gain. In conclusion, HFol diets fed to rat dams and their offspring affect area and strength of femurs and mineral quantity but not strength of lumbar vertebrae in the offspring.

Effect of paracetamol treatment on maternal care and reproductive outcomes in female rat offspring

2020 ◽  
Vol 32 (18) ◽  
pp. 1311
Author(s):  
Jeberson F. Aleixo ◽  
Marina R. F. Pereira ◽  
Bruno G. Montagnini ◽  
Matheus Junior D. Pereira ◽  
Simone Forcato ◽  
...  
Keyword(s):  
Sexual Development ◽  
Maternal Care ◽  
Wistar Rats ◽  
Reproductive Behaviour ◽  
Female Offspring ◽  
Female Rat ◽  
Anogenital Distance ◽  
Rat Offspring ◽  
Grooming Behaviour ◽  
Plasma Oestradiol

Paracetamol (PAR) is one of the most commonly used drugs by pregnant women because it is considered safe for the mother and fetus. However, PAR is transferred into breast milk and crosses the blood–placental barrier, being present in the progeny during important stages of development. Intrauterine exposure to PAR may decrease the anogenital distance and follicle reserve in female rodent offspring. Therefore, the aim of the present study was to evaluate whether maternal PAR treatment altered the reproductive behaviour of dams and the sexual development of female rat offspring. Pregnant Wistar rats were gavaged daily with 350mg kg−1 day−1 PAR or water during gestation (from Gestation Day (GD) 6 until delivery) or during gestation and lactation (from GD6 until weaning). Maternal PAR treatment had maternal effects (increased grooming behaviour), and resulted in impaired sexual behaviour, decreased follicle reserve and increased plasma oestradiol concentrations in female offspring.

scholarly journals Late introduction of low dose resveratrol and grape powder after estradiol depletion does not restore glucose tolerance in the ovariectomized rat.

2018 ◽  
Vol 8 (2) ◽  
pp. 79
Author(s):  
Eoin Anderson ◽  
Dan Cervone ◽  
David James Dyck
Keyword(s):  
Glucose Tolerance ◽  
Body Mass ◽  
Glucose Intolerance ◽  
Low Dose ◽  
Time Window ◽  
Critical Time ◽  
Grape Pomace ◽  
Delayed Treatment ◽  
Insulin Tolerance ◽  
Ovx Rats

Background: Estrogen (E2) loss is associated with insulin resistance. Natural compounds such as resveratrol (RESV) have potential insulin sensitizing effects. Grape pomace powder (GP) also contains RESV and other antioxidants. However, the ability of realistic, attainable concentrations of RESV and GP to reverse glucose intolerance in E2 deficient rats has not yet been explored.Purpose: The aim of the current study was to determine whether RESV and GP, in realistic amounts that could be achieved with supplementation, would be effective in restoring glucose tolerance in the ovariectomized (OVX) rat. Furthermore, there appears to be a critical time window following the loss of E2 when hormonal replacement is effective, with delayed treatment being ineffective and potentially detrimental. Therefore, we were particularly interested in examining the effectiveness of RESV and GP as a delayed treatment i.e. after the establishment of glucose intolerance, rather than administering at the onset of E2 loss. Results: In the present study, rats demonstrated impaired glucose tolerance, as determined by an intraperitoneal glucose tolerance test, 12 weeks after bilateral ovary removal. Subsequently, OVX animals were randomly placed into a sham or one of 3 treatment groups. The treatments were either i) a physiological oral dose of E2 (28µg/kg body mass), ii) RESV (5mg/kg body mass), or iii) GP (1.5g/100g of diet) for another 6 weeks. OVX animals were significantly heavier than non-OVX rats at the onset of glucose intolerance and this did not change throughout the treatment. None of the treatments restored glucose tolerance within the 6 weeks. Insulin tolerance did not worsen in OVX rats and was unaffected by treatment. Adipocyte size was generally increased in OVX animals and was not decreased with treatment.Conclusions: In conclusion, delayed E2, RESV and GP treatment do not restore glucose tolerance in OVX rats. Low dose RESV and GP supplementation may not be effective alternatives to HRT to restore compromised glucose tolerance.         Keywords: ovariectomy, estrogen, resveratrol, grape pomace, glucose tolerance, insulin tolerance, delayed treatment

scholarly journals Reproductive physiology, and physical and sexual development of female offspring born to diabetic dams

2012 ◽  
Vol 56 (2) ◽  
pp. 96-103 ◽  
Author(s):  
Raquel Spadotto ◽  
Débora Cristina Damasceno ◽  
Antonio Francisco Godinho ◽  
Elaine Manoela Porto Amorim ◽  
Juliana Elaine Perobelli ◽  
...  
Keyword(s):  
Sexual Development ◽  
Maternal Diabetes ◽  
Female Offspring ◽  
Physical Development ◽  
Reproductive Physiology ◽  
Female Rats ◽  
Histological Evaluation ◽  
Control Group ◽  
Female Rat ◽  
Rat Offspring

OBJECTIVES: The objective of this study was to evaluate physical and sexual development and reproductive physiology in female rat offspring that developed in hyperglycemia conditions in utero and during lactation. MATERIALS AND METHODS: Maternal diabetes was induced in female rats by a single IV injection of streptozotocin before mating. Female offspring development was evaluated by means of the following parameters: physical development; age of vaginal opening and first estrus; weight and histological evaluation of uterus and ovaries; duration of the estrous cycle, sexual behavior, and fertility after natural mating. RESULTS: In the female offspring, maternal diabetes caused delays in initial physical development; diminution in ovary weight and number of follicles; and inferior reproductive performance compared with the control group. CONCLUSIONS: The exposure to hyperglycemia in uterus and during lactation caused delays in physical and sexual development, and affected the reproductive physiology of female rats negatively.

scholarly journals Protein restriction during pregnancy induces hypertension in adult female rat offspring – influence of oestradiol

2011 ◽  
Vol 107 (5) ◽  
pp. 665-673 ◽  
Author(s):  
K. Sathishkumar ◽  
Rebekah Elkins ◽  
Uma Yallampalli ◽  
Chandra Yallampalli
Keyword(s):  
Adult Female ◽  
Female Offspring ◽  
Protein Restriction ◽  
Intact Protein ◽  
Female Rat ◽  
Pregnant Rats ◽  
Testosterone Levels ◽  
Induced Hypertension ◽  
Plasma Oestradiol

We previously reported that gestational dietary protein restriction in rats causes sex-related differences in development of blood pressure (BP) in the offspring, which is more pronounced in males than in females. As such effects may depend on sex hormones, we investigated the role of oestradiol in the development of hypertension in female offspring of protein-restricted dams. Female offspring of pregnant rats fed normal (20 %) or protein-restricted (6 %) casein diets throughout pregnancy were kept either intact, ovariectomised or ovariectomised with oestradiol supplementation. BP, Plasma oestradiol and testosterone levels, and vascular oestrogen receptor (ER) were examined. BP was significantly higher and plasma oestradiol levels were significantly lower ( − 34 %) in intact protein-restricted female offspring compared to corresponding controls. Further decrease in oestradiol levels by ovariectomy exacerbated hypertension in the protein-restricted females, with an earlier onset and more prominent elevation in BP compared to controls. Oestradiol supplementation in ovariectomised protein-restricted females significantly reversed ovariectomy-induced hypertension but did not normalise BP to control levels. The hypertensive protein-restricted females have reduced vascular ERα expression that was unaffected by ovariectomy or oestradiol replacement. In addition, testosterone levels were significantly higher by 2·4-, 3·4- and 2·8-fold in intact, ovariectomised and oestradiol-replaced protein-restricted females compared to corresponding controls. The present data show that: (1) hypertension in protein-restricted adult female offspring is associated with reduced plasma oestradiol levels; (2) oestradiol protects and limits the severity of hypertension in protein-restricted females and contributes to sexual dimorphism; (3) oestradiol replacement fails to completely reverse hypertension, which may be related to limited availability of vascular ERα receptors and/or increased circulating testosterone levels.

scholarly journals ORMDL3 regulates poly I:C induced inflammatory responses in airway epithelial cells

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Gemma Laura ◽  
Yi Liu ◽  
Kieran Fernandes ◽  
Saffron A. G. Willis-Owen ◽  
Kazuhiro Ito ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Inflammatory Response ◽  
Viral Infection ◽  
Airway Epithelial Cells ◽  
Poly I:C ◽  
Synthetic Analog ◽  
Mrna Levels ◽  
Airway Epithelial ◽  
Over Expression ◽  
Polycytidylic Acid

Abstract Background Oroscomucoid 3 (ORMDL3) has been linked to susceptibility of childhood asthma and respiratory viral infection. Polyinosinic-polycytidylic acid (poly I:C) is a synthetic analog of viral double-stranded RNA, a toll-like receptor 3 (TLR3) ligand and mimic of viral infection. Methods To investigate the functional role of ORMDL3 in the poly I:C-induced inflammatory response in airway epithelial cells, ORMDL3 knockdown and over-expression models were established in human A549 epithelial cells and primary normal human bronchial epithelial (NHBE) cells. The cells were stimulated with poly I:C or the Th17 cytokine IL-17A. IL-6 and IL-8 levels in supernatants,  mRNA levels of genes in the TLR3 pathway and inflammatory response from cell pellets were measured. ORMDL3 knockdown models in A549 and BEAS-2B epithelial cells were then infected with live human rhinovirus (HRV16) followed by IL-6 and IL-8 measurement. Results ORMDL3 knockdown and over-expression had little influence on the transcript levels of TLR3 in airway epithelial cells. Time course studies showed that ORMDL3-deficient A549 and NHBE cells had an attenuated IL-6 and IL-8 response to poly I:C stimulation. A549 and NHBE cells over-expressing ORMDL3 released relatively more IL-6 and IL-8 following poly I:C stimulation. IL-17A exhibited a similar inflammatory response in ORMDL3 knockdown and over-expressing cells, but co-stimulation of poly I:C and IL-17A did not significantly enhance the IL-6 and IL-8 response. Transcript abundance of IFNB following poly I:C stimulation was not significantly altered by ORMDL3 knockdown or over-expression. Dampening of the IL-6 response by ORMDL3 knockdown was confirmed in HRV16 infected BEAS-2B and A549 cells. Conclusions ORMDL3 regulates the viral inflammatory response in airway epithelial cells via mechanisms independent of the TLR3 pathway.

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