Pregnant Female Mice Research Articles

In Utero Exposure to Maternal Electronic Nicotine Delivery System use Demonstrate Alterations to Craniofacial Development.

Develop a model for the study of Electronic Nicotine Device (ENDS) exposure on craniofacial development. Experimental preclinical design followed as pregnant murine dams were randomized and exposed to filtered air exposure, carrier exposure consisting of 50% volume of propylene glycol and vegetable glycine (ENDS Carrier) respectively, or carrier exposure with 20 mg/ml of nicotine added to the liquid vaporizer (ENDS carrier with nicotine). Preclinical murine model exposure using the SciReq exposure system. C57BL6 adult 8 week old female pregnant mice and exposed in utero litters. Exposure to control filtered air, ENDS carrier or ENDS carrier with nicotine added throughout gestation at 1 puff/minute, 4 h/day, five days a week. Cephalometric measures of post-natal day 15 pups born as exposed litters. Data suggests alterations to several facial morphology parameters in the developing offspring, suggesting electronic nicotine device systems may alter facial growth if used during pregnancy. Future research should concentrate on varied formulations and exposure regimens of ENDS to determine timing windows of exposures and ENDS formulations that may be harmful to craniofacial development.

The Ethanolic Extract of Piper glabratum Kunth Is Teratogenic and Interferes with the Ossification Process of Swiss Mice Fetuses

Piper glabratum Kunth is a plant traditionally used to treat pain and inflammation in the Mato Grosso do Sul, Brazil. Even pregnant women consume this plant. Toxicology studies of the ethanolic extract from the leaves of P. glabratum (EEPg) could establish the safety of popular use of P. glabratrum. Thus, the effects of the ethanolic extract of leaves of P. glabratum (EEPg) on the reproductive performance and embryofetal development of Swiss mice were evaluated. Pregnant female mice were treated with 100, 1000 and 2000 mg/kg throughout the gestational period by gavage (p.o). The control group received the EEPg vehicle (Tween 80-1%) in the proportion of 0.1 mL/10 g (p.o.). The results demonstrated that EEPg has low maternal toxic potential and does not alter the reproductive performance of females. However, it altered embryofetal development and caused fetal weight reduction (increasing the frequency of small-for-gestational-age fetuses) at the two highest doses. In addition, it interfered with placental weight, placental index and placental efficiency. The frequency of visceral malformations increased by 2.8 times for the lowest dose of EEPg, and skeletal malformations increased by 2.48, 1.89 and 2.11 times for doses of 100, 1000 and 2000 mg/kg of EEPg, respectively. It is noteworthy that 100% of the offspring treated with EEPg showed changes in the ossification process. Thus, it is considered that the EEPg has low maternal toxic potential; it does not alter the reproductive performance of females. However, it is teratogenic and interferes, mainly, in the ossification process, and therefore its use is contraindicated in the gestational period.

Effect of Maternal Gradient Nutritional Restriction during Pregnancy on Mammary Gland Development in Offspring.

We aimed to investigate the effect of different levels of nutritional restriction on mammary gland development during the embryonic period by gradient nutritional restriction in pregnant female mice. We started the nutritional restriction of 60 female CD-1(ICR) mice from day 9 of gestation based on 100%, 90%, 80%, 70% and 60% of ad libitum intake. After delivery, the weight and body fat of the offspring and the mother were recorded (n = 12). Offspring mammary development and gene expression were explored by whole mount and qPCR. Mammary development patterns of in offspring were constructed using Sholl analysis, principal component analysis (PCA) and regression analysis. We found that: (1) Mild maternal nutritional restriction (90-70% of ad libitum intake) did not affect offspring weight, while body fat percentage was more sensitive to nutritional restriction (lower at 80% ad libitum feeding). (2) A precipitous drop in mammary development and altered developmental patterns occurred when nutritional restriction ranged from 80% to 70% of ad libitum intake. (3) Mild maternal nutritional restriction (90% of ad libitum intake) promoted mammary-development-related gene expression. In conclusion, our results suggest that mild maternal nutritional restriction during gestation contributes to increased embryonic mammary gland development. When maternal nutritional restriction reaches 70% of ad libitum intake, the mammary glands of the offspring show noticeable maldevelopment. Our results help provide a theoretical basis for the effect of maternal nutritional restriction during gestation on offspring mammary development and a reference for the amount of maternal nutritional restriction.

O7-2 - SARS-CoV-2 infection in pregnant female mouse featured as delayed anti-viral response

O7-2 - SARS-CoV-2 infection in pregnant female mouse featured as delayed anti-viral response

Effect of troxerutin consumption during gestation period on reflexive motor behavior in mice offspring.

This study aimed to determine the effects of troxerutin consumption during gestation on reflexive motor behavior in mice offspring. Forty pregnant female mice were allocated into four groups. In the control group, mice received water, while in groups 2-4, female mice p.o. administered troxerutin (50, 100, and 150 mg/kg) at 5, 8, 11, 14, and 17 days of gestation (GD). Following delivery, pups were selected based on their experimental group, and reflexive motor behaviors were determined. Also, serum malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), and total antioxidant status (TAS) were determined. Based on the findings, maternal exposure to troxerutin (100 and 150 mg/kg) increased ambulation scores in offspring's compared with control group (P <0.05). Also, prenatal exposure to troxerutin increased front- and hind-limb suspension scores in newborns compared with control group (P <0.05). Maternal exposure to troxerutin increased grip strength and negative geotaxis in newborns in comparison with control mice (P <0.05). Prenatal exposure to troxerutin (100 and 150 mg/kg) decreased hind-limb foot angle and surface righting in pups compared with control group (P <0.05). Maternal exposure to troxerutin decreased MDA production and increased SOD, GPx, and TAS levels in offspring (P <0.05). These results suggested that prenatal consumption of the troxerutin improves reflexive motor behaviors in mice pups.

Reproductive Toxicity of Sodium Nitrite and Its Modulation by Ascorbic Acid as An Antioxidant in Pregnant Female Mice

Reproductive Toxicity of Sodium Nitrite and Its Modulation by Ascorbic Acid as An Antioxidant in Pregnant Female Mice

Effects of swimming before and during pregnancy on placental angiogenesis and perinatal outcome in high-fat diet-fed mice.

We explored the mechanism underlying exercise-mediated placental angiogenesis and perinatal outcome using mouse models. Three-week-old C57BL/6 female mice were randomly divided into four experimental groups: standard-chow diet (SC), standard chow diet + exercise (SC-Ex), high-fat diet (HFD), and high-fat diet + exercise (HFD-Ex). After 13 weeks of exercise intervention, the male and female mice were caged. Approximately six to seven pregnant female mice from each experimental group were randomly selected for body composition, qRT-PCR, histological, and western blot analysis. The remaining mice were allowed to deliver naturally, and the perinatal outcome indexes were observed. The results showed that exercise intervention significantly improved the body composition and glucose tolerance in HFD-fed pregnant mice. The HFD group showed adipocyte infiltration, placental local hypoxia, and villous vascular thrombosis with a significant (p < 0.05) increase in the expression of VEGF and ANGPT1 proteins. Exercise intervention significantly elevated the expression of PPARγ, alleviated hypoxia and inflammation-related conditions, and inhibited angiogenesis. sFlt-1 mRNA in HFD group was significantly higher than that in SC group (p < 0.05). Furthermore, the HFD significantly reduced (p < 0.05) the fertility rate in mice. Thus, HFD aggravates placental inflammation and the hypoxic environment and downregulates the expression of PPARγ and PPARα in the placenta. However, exercise intervention can significantly alleviate these conditions.

Green synthesis and characterization of silver nanoparticles for reducing the damage to sperm parameters in diabetic compared to metformin

The present study used physics to synthesize silver nanoparticles using aqueous extract of fresh garlic as reducing and as a stabilizing agent silver nitrate solution. This method has proven to be environmentally friendly and safe for the synthesis of stable silver nanoparticles. The acquisition of silver nanoparticles was confirmed by optical detection, that is, by changing the color of the liquid to transparent orange and then blackish brown. Then, the characterization was confirmed using other assays. In this study, it was found that the absorption peak of silver nanoparticles was at a wavelength of 420 nm and the particle size ranged between [50–350] nm. The surface roughness of silver oxide/silver nanoparticles was 9.32 nm with an average square roughness of 21.19 nm, and the energy dispersive spectra showed that the absorption peak was in the region of 3 keV, indicating that the nanoparticles contained crystalline silver. In this study, the stability of the silver nanoparticles was good, as ZP reached (− 19.5). The results confirm that the conductivity increases with the increase in frequency due to the high energy of the photons, which causes the electrons to vibrate in the energy levels and thus increase the energy in the mitochondria and increase the movement of sperm in the Diabetic mice treated with doses of silver nanoparticles. The toxic effect of silver nanoparticles has been evaluated in other studies, in addition to evaluating antioxidants, antifungals, treating cancer cells, regulating cholesterol levels, the effect of these nanoparticles on sex cells in pregnant female mice, heart tension, and many other tests. In this study, the activities and efficacy of silver nanoparticles on sperms were determined in male mice with diabetes caused by STZ, and the treatment period was long (35 days) so that the evaluation period was a complete life cycle of male sex cells and within a long period of time and at an average nano size. This has not been studied in other previous studies. The results indicate that the biosynthesis of silver nanoparticles using garlic plant led to positive results on sperm treatments by contributing to an increase in the number of sperm with reactivation and a decrease in abnormalities in addition to a decrease in mortality due to diabetes. This is evidence that the synthesis of silver nanoparticles using garlic plant size (50–350 nm) can treat impotence and be used in the future in the treatment of many diseases without side effects.

The therapeutic effect of melatonin on female offspring ovarian reserve and quality in BALB/c mice after exposing their mother to methamphetamine during pregnancy and lactation.

Nowadays, methamphetamine (METH) abuse as a psychotropic drug is increasing. There is insufficient information about its adverse effects on the ovarian reserve of the next generation. Herein, we tried to investigate the effect of METH abuse during pregnancy and lactation and, subsequently, the therapeutic effect of melatonin on ovarian reserve in offspring. In the present study, BALB/c pregnant female mice were divided into 3 groups: Control, Saline, and METH (5mg/Kg). METH was injected during pregnancy and lactation, and the female offspring of each group was divided into 2 subgroups: A) treated with 10 mg/kg Melatonin daily until puberty (6 weeks old) and B) received distilled water. The animals were sacrificed at 6 weeks of age, and blood samples were collected for hormonal assessments; the right ovaries were removed and fixed for TUNEL and Hematoxylin & Eosin staining, and the left ovaries were removed and stored for gene expression and oxidative stress evaluation. In the MTEH group, two indicators of ovarian reserve (including anti-Müllerian hormone (AMH) and primordial follicle, and Cyclin D1 (CCND-1) and proliferating cell nuclear antigen (PCNA) genes expression significantly decreased, and the oxidative stress and apoptosis significantly increased in comparison with other groups. After lactation in the MTEH group, melatonin treatment significantly improved the ovarian reserve and gene expression and declined apoptosis and oxidative stress. METH abuse during pregnancy and lactation decreased ovarian reserve in offspring. The administration of melatonin as an anti-oxidant agent after lactation can counteract the adverse effects of METH on offspring ovaries.

Pups and prolactin are rewarding to virgin female and pregnant mice.

Maternal interactions with offspring are highly rewarding, which reinforces expression of essential caregiving behaviours that promote offspring survival. In rats, the rewarding effect of pups depends on reproductive state, with lactating females specifically developing strong preferences for pup-associated contexts. Whether this also occurs in mice is unknown, hence we aimed to characterise pup-related preference across reproductive states in female mice. In a conditioned place preference (CPP) test, pups were a rewarding stimulus to female mice prior to lactation, with virgin and pregnant females developing a preference for a pup-associated context. We have previously shown that lactogenic hormones, acting through the prolactin receptor (Prlr), play an important role in maternal motivation. Here, we aimed to investigate whether Prlr action is important for pup-related reward behaviour in mice. We showed that prolactin itself had a reinforcing effect in a CPP test, and that exposure to pups increased blood prolactin levels in virgin female mice. Prlr expression in CamKIIα-expressing neurons and GABAergic neurons has previously been shown to be important for different aspects of parental behaviour. However, we found that conditional Prlr deletion from either of these neuronal populations did not disrupt the development of a preference for pup-associated contexts in pregnant female mice, indicating that lactogenic action on these populations is not necessary for the rewarding effect of pups. Together, these data show that while lactogenic hormones likely contribute to a rewarding effect of pups, their action on two key neuronal populations is not necessary for this effect in female mice.

MILK CONSUMPTION AFFECTS THE EXPRESSION OF AMELOGENIN IN AMELOBLAST CELLS DURING AMELOGNESIS (IN VIVO ANALYSIS OF PREGNANT MICE)

Background: Tooth development during embryonic period is complex process that needs enough nutrition for the formation of healthy dental tissue. Amelogenin are proteins that are secreted by ameloblast in the secretory stage that are importants in the crystal formation and the regulation of email thickness. Milk consumption during pregnancy can increase the expression of amelogenin of ameloblas cell in the tooth development process. This research aims to determine the impact of milk during pregnancy against the expression of amelogenin protein of ameloblast cell in the amelogenesis.Method: This is a true experimental laboratories research using post test only control group design. A total of 12 pregnant female mice (Mus Musculus L.) are used and divided into 2 groups, control group (given sterile aquades) and treatment group (given pregnancy milk). The measurements of amelogenin expression are done in 18th day of pregnancy period. Data were analyzed using Independent sampel of T-test analysis.Result: The result of this study showed that the average amounts of amelogenin expression in the treatment group are lower than the control group. Independent sampel t-test showed that there are significant difference in the amount of amelogenin expression between the control and treatment group (P&gt;0,05)Conclusion: The milk consumption during pregnancy influenced the amelogenin expression of ameloblast cell in the mice fetus’s amelogenesis.

Plasmodium berghei infection associated with adverse birth outcomes in pregnant Swiss albino mice

Malaria in pregnancy has been seen to cause poor pregnancy and foetal outcomes. In this study, mice infected with Plasmodium berghei (P. berghei) during the second and third stages of pregnancy were examined for their pregnancy's outcome and changes in their blood's biochemical composition after delivery. Additionally, the physical and behavioural reactions of the mice's pups were also investigated. Thirty pregnant female Swiss Albino mice were randomly divided into three groups; two received intraperitoneal injections of 106 P. berghei-infected red blood cells on gestational days (GD12 and 17), while the third group was left uninfected (control). Pregnancy termination occurred in 20% of mice infected during GD12, whereas mortality before parturition occurred in 40% and 30% of mice infected during GD12 and GD17, respectively. Non-infected group's total protein and glucose concentrations were significantly higher (p&lt;0.05), while cholesterol and triglyceride concentrations were significantly lower (p&lt;0.05) when compared to the infected groups. The Mean birth weights (1.82 ± 0.37 g) of pups were considerably higher (p &lt; 0.05) in control mice compared to pups from infected groups. Offspring born to infected mothers exhibited poor physical and behavioural responses. Mice infection by Plasmodium berghei during pregnancy resulted in adverse birth outcomes, altered measured biochemical parameters, poor physical and behavioural responses in their offspring and was more severe during the 2nd stage of pregnancy.

Prenatal Exposure to L-Citrulline Has Positive Effects on Reflexive Motor Behavior in Newborn Mice.

L-citrulline (L-cit) is a nonessential amino acid that interacts with the veracity of neurotransmitters in the brain and might have a positive effect on fetal growth. However, there is no information about the possible effect of L-cit on reflexive motor behavior. Thus, this study aimed to determine the effects of prenatal exposure to L-cit on reflexive motor behavior in mice offspring. Forty pregnant female mice were allocated into four groups. In the control group, mice received water, while in groups 2-4, female mice orally gavage with L-cit (25, 50, and 100 mg/kg) at 5, 8, 11, 14, and 17 days of gestation (GD). Following delivery, pups were selected, and reflexive motor behaviors were determined using ambulation, hind-limb foot angle, surface righting, hind-limb strength, grip strength, front limb suspension, and negative geotaxis tests. Also, serum Nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPx) were determined. Based on the findings, maternal exposure to L-cit improved ambulation score, hind-limb suspension score, grip strength, and front-limb suspension in offspring (P<0.05). Prenatal exposure to L-cit decreased surface righting, hind-limb foot angle, and negative geotaxis in offspring (P<0.05). L-cit decreased immobility time in forced swimming test (FST), tail suspension test (TST), and increased number of squares crossed in the open field test (OFT) and spending time on rotarod on postpartum mice (P<0.05). L-cit increased serum NO levels (P<0.05). L-cit decreased blood MDA and increased SOD and GPx levels in offspring (P<0.05). Findings revealed that L-cit improves postpartum behaviors in mice and reflexive motor in their pups.

Gingerol fractions bioactivity against butanone cytotoxicity induced in newborns of mice.

Accumulating studies have demonstrated the potential activity of ginger in treating and managing several diseases but little is known about its protective effects against teratogenicity of chemical toxins. Thus, in this study, we have evaluated the protective effect of gingerol fraction (GF) against methyl ethyl ketone (MEK) induced teratogenic effects in newborns of mice. A total of 30 mature females and fifteen male mice (Mus musculus) weighing 25-30 g were included in this study. The pregnant mice were divided into three groups (10 mice each); control group (GI, mice received normal drinking water; NDW), methyl ethyl ketone (MEK) treated group (GII, received MEK at a dose of 350 mg/kg body weight in NDW), and GF treated group (GIII; mice received GF at a dose of 25 mg/kg in NDR). Histological analysis, cellular oxidative, and antioxidant enzymes, fibrosis, and apoptosis of brain, liver, and kidney tissues were estimated by histological and immunoassay techniques. In this study, the treatment of pregnant female mice with gingerol fractions (GF) at a dose of 25 mg/kg significantly protected all tissues organs of mothers and their offspring against the teratogenic effects induced by MEK at a dose of 350 mg/kg. A significant improvement in cellular antioxidant enzymes GSH, SOD, and peroxidase activities along with a reduction in the initiation of cellular oxidative free radicals (TBARS) was reported in GF treated mice compared to mice intoxicated with MEK (350 mg/kg). In addition, a significant reduction in cellular fibrosis and apoptosis was reported in all tissues of mothers and their offspring's following treatment with GF. HPLC analysis of ginger extracts estimated a set of polyphenolic compounds such [6]-gingerol, [8]-gingerol, [10]-gingerol, and [6]-shogaol which are responsible for the antioxidant, anti-fibrotic, and anti-apoptotic protective effects against teratogenic effects of MEK. Gingerol fractions (GF) at a dose of 25 mg/kg significantly protected all tissues organs of mothers and their offspring against the teratogenic effects induced by MEK at a dose of 350 mg/kg. The beneficial effects of ginger phenolic compounds; [6]-gingerol, [8]-gingerol, [10]-gingerol, and [6]-shogaol against teratogenic effects of MEK proceeded through their antioxidant, anti-fibrotic, and anti-apoptotic properties.

Effect of Ethanol Consumption on the Placenta and Liver of Partially IGF-1-Deficient Mice: The Role of Metabolism via CYP2E1 and the Antioxidant Enzyme System

Simple SummaryEthanol is the most consumed drug worldwide, even during pregnancy. One of its adverse outcomes is fetal growth restriction, an alteration in development due to decreased IGF-1 levels. Several studies have shown that ethanol can impair the IGF-1 signaling pathway, thus exacerbating IGF-1 adverse effects in both intrauterine and postnatal growth and development. In this manuscript, we used a partially IGF-1-deficient mouse model to demonstrate the key role of IGF-1 in fetal development, as well as ethanol’s adverse effects on CYP2E1 expression levels and the antioxidant enzyme system during pregnancy.Ethanol use during pregnancy is a risk factor for developing adverse outcomes. Its metabolism by cytochrome P450 2E1 (CYP2E1) produces radical oxygen species (ROS), promoting cellular injury and apoptosis. To date, no studies have been conducted to elucidate the teratogenic effects due to both IGF-1 deficiency and ethanol consumption in mice placentas. The aim of this study is to determine the effect of ethanol consumption on the placenta and liver of partially IGF-1-deficient mice, the role of metabolism via CYP2E1, and the antioxidant enzyme system. Heterozygous (HZ, Igf1+/−) pregnant female mice were given water or 10% ethanol. Wild-type (WT, Igf1+/+) female mice were used as controls. At gestational day 19, pregnant dams were euthanized, and maternal liver and placentas were collected. Pregnant HZ dams were smaller than controls, and this effect was higher due to ethanol consumption. Cyp2e1 gene was overexpressed in the liver of HZ pregnant dams exposed to ethanol; at the protein level, CYP2E1 is reduced in placentas from all genotypes. The antioxidant enzymatic system was altered by ethanol consumption in both the maternal liver and placenta. The results in this work hint that IGF-1 is involved in intrauterine development because its deficiency exacerbates ethanol’s effects on both metabolism and the placenta.

Bacopa monnieri extract ameliorates core autistic behavioural deficits of sodium valproate-induced autism spectrum disorder in mice, and its mechanism of action related to PTEN protein

Our previous study demonstrated the effect of Bacopa monnieri extract (BME) on behavioural deficits in sodium valproate (VPA)-induced autism spectrum disorder in mice. The present study aims to further investigate the effect of BME on neurobehaviors of autism spectrum disorder (ASD) in mice and the biochemical mechanism(s) involved. Female pregnant mice were divided into control and VPA treated groups at 12-13 days of gestation (saline/sodium valproate 500 mg/kg respectively, i.p.). Control group pups of saline-treated mothers received distilled water. The VPA-treated mothers received either distilled water or BME (50 mg/kg, p.o.) after birth until 13 days later. Then, from postnatal day 14, ASD pups were orally treated with BME (50 mg/kg)/distilled water for the duration of the study. Behavioural deficits (repetitive behaviour and social behaviour deficit) were measured by a self-grooming test and a three-chamber test on postnatal days 20 and 30. On postnatal day 40, the cerebral cortex of pups was isolated for evaluation of the expression level of PTEN protein using the Western blot method. The results showed that BME (50 mg/kg, p.o.) significantly improved repetitive behaviour and social behaviour deficits in ASD mice on postnatal day 20 and 30, and also increased PTEN protein expression level in the brain of ASD mice. These results demonstrated that BME ameliorates core behaviours of autism and concurrently restores decreases in PTEN protein expression in the cerebral cortex of valproate-treated mice.

Serotonin limits generation of chromaffin cells during adrenal organ development

Adrenal glands are the major organs releasing catecholamines and regulating our stress response. The mechanisms balancing generation of adrenergic chromaffin cells and protecting against neuroblastoma tumors are still enigmatic. Here we revealed that serotonin (5HT) controls the numbers of chromaffin cells by acting upon their immediate progenitor “bridge” cells via 5-hydroxytryptamine receptor 3A (HTR3A), and the aggressive HTR3Ahigh human neuroblastoma cell lines reduce proliferation in response to HTR3A-specific agonists. In embryos (in vivo), the physiological increase of 5HT caused a prolongation of the cell cycle in “bridge” progenitors leading to a smaller chromaffin population and changing the balance of hormones and behavioral patterns in adulthood. These behavioral effects and smaller adrenals were mirrored in the progeny of pregnant female mice subjected to experimental stress, suggesting a maternal-fetal link that controls developmental adaptations. Finally, these results corresponded to a size-distribution of adrenals found in wild rodents with different coping strategies.

Parental exposure of Tadalafil has beneficial effect on reflexive motor behaviors in mice offspring.

Tadalafil has positive effects on neurodevelopment and antioxidant defense system, but there is no information for its possible role during gestation on reflexive motor behavior in offspring. So current study determined the effect of prenatal exposure to the Tadalafil on reflexive motor behaviors and antioxidant activity in mice offspring and antidepressive behaviors in postpartum dams. Forty pregnant female NMRI mice were allocated into four groups. In control group, mice received water while in Groups 2-4, female mice orally gavage with Tadalafil (0.4, 0.8, and 1.6mg/kg) at gestation day (GD) 5, 8, 11, 14, and 17, respectively. Following delivery, pups were selected and reflexive motor behaviors determined using ambulation, hind-limb foot angle, surface righting, hind-limb strength, grip strength, front-limb suspension, and negative geotaxis tests. Also, serum malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), and total antioxidant status (TAS) were determined in offspring. On Day 2 postpartum, antidepressant activity of Tadalafil was determined by open field test (OFT), rotarod, forced swimming test (FST), and tail suspension test (TST) in dams. Based on the findings, maternal exposure to Tadalafil improved ambulation score, hind-limb suspension score, grip strength, and front-limb suspension in offspring (P < 0.05). Prenatal exposure to Tadalafil decreased surface righting, hind-limb foot angle, and negative geotaxis in offspring (P < 0.05). Tadalafil decreased blood MDA and increased SOD and GPx levels in offspring (P < 0.05). Tadalafil significantly decreased immobility time in FST and TST and increased number of squares crossed in OFT and spending time on rotarod on postpartum mice (P < 0.05). These results suggested that parental exposure of Tadalafil has positive effect on reflexive motor and postpartum behaviors.

Direct Injection of Recombinant AAV-Containing Solution into the Oviductal Lumen of Pregnant Mice Caused In Situ Infection of Both Preimplantation Embryos and Oviductal Epithelium.

Adeno-associated virus (AAV) vector is an efficient viral-based gene delivery tool used with many types of cells and tissues, including neuronal cells and muscles. AAV serotype 6 (AAV-6), one of numerous AAV serotypes, was recently found to efficiently transduce mouse preimplantation embryos. Furthermore, through coupling with a clustered, regularly interspaced, short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) system—a modern genome editing technology—AAV-6 has been shown to effectively create a mutation at a target locus, which relies on isolation of zygotes, in vitro viral infection, and transplantation of the infected embryos to recipient females. Unfortunately, this procedure, termed “ex vivo handling of embryos”, requires considerable investment of capital, time, and effort. Direct transduction of preimplantation embryos through the introduction of AAV-6 into the oviductal lumen of pregnant females would be an ideal approach. In this study, we injected various types of recombinant AAV vectors (namely, rAAV-CAG-EGFP-1, -2, -5, and -6, each carrying an enhanced green fluorescent protein [EGFP] cDNA whose expression is under the influence of a cytomegalovirus enhancer + chicken β-actin promoter) into the ampulla region of oviducts in pregnant female mice at Day 0.7 of pregnancy (corresponding to the late 1-cell stage), and EGFP-derived green fluorescence was assessed in the respective morulae. The highest levels of fluorescence were observed in rAAV-CAG-EGFP-6. The oviductal epithelium was distinctly fluorescent. The fluorescence in embryos peaked at the morula stage. Our results indicate that intra-oviductal injection of AAV-6 vectors is the most effective method for transducing zona pellucida-enclosed preimplantation embryos in situ. AAV-6 vectors could be a useful tool in the genetic manipulation of early embryos, as well as oviductal epithelial cells.

Maternal exposure to glyphosate-based herbicide promotes changes in the muscle structure of C57BL/6 mice offspring.

Glyphosate (GBH) is a worldwide consumption pesticide and is used in the formulation of Roundup®, one of the most commercialized herbicides in the world. Maternal exposure to this herbicide can promote changes and adaptations in the offspring; however, the effects on skeletal muscle are poorly understood. In this sense, the present study sought to evaluate the effect of exposure to GBH on the characteristics of the soleus (SOL) and extensor digitorum longus (EDL) muscles. C57BL/6 pregnant female mice were divided into two groups: control (CTL) receiving water and glyphosate (GBH; n=6) receiving 0.5% glyphosate. Male puppies were designated according to the group to which the mothers belonged, such as CTL-F1 and GBH-F1 and then euthanized at 150 days of age. There was a reduction in body weight and nasoanal length of animals exposed to GBH, while there was an increase in EDL weight, reduction in the proportion of fibers and number of nuclei, and an increase in the connective tissue of the SOL. The animals exposed to GBH presented higher values of body characteristics, mainly adiposity gain, while they presented a reduction in neuromuscular junctions (NMJ), and an increase in fibrosis in the SOL muscle, while there was a reduction in the number of nuclei, and an increase in the weight of the EDL muscle. These findings indicate that glyphosate can promote changes in the offspring's body growth, the deposition of adipose panicles and its effects on muscle can lead to changes in the structure and functioning of this tissue.