Female NMRI Mice Research Articles

Mesenchymal Stromal Cell Exosome-Induced Vascular Regeneration in a PCOS Mouse Model.

The efficacy of Bone Marrow Mesenchymal Stem Cell-derived Exosomes (BMSCs-Exo) in addressing the complexities of Polycystic Ovary Syndrome (PCOS) has been explored in a controlled experimental study using a DHEA-induced PCOS model in 6-8-week-old female NMRI mice. This research undertook an in vivo approach with fifteen female murine subjects to investigate the potential of BMSCs-Exo in promoting vascular regeneration and alleviating the adverse effects associated with PCOS. Through a strategic intervention, the study aimed to modulate the pathophysiological markers of oxidative stress and inflammation that are hallmark features of PCOS. Remarkably, the administration of BMSCs-Exo led to decreased CD31 expression in ovarian tissues, suggesting reduced angiogenesis and endothelial activation. Moreover, a significant reduction in pro-inflammatory cytokines and oxidative stress markers was noted, aligning closely with the metrics observed in the control group. These findings illuminate a promising therapeutic avenue utilizing BMSCs-Exo to recalibrate angiogenic, inflammatory, and oxidative stress responses in PCOS. This research not only contributes to the current understanding of PCOS management but also opens new doors for innovative clinical treatments.

A systematic assessment of robustness in CNS safety pharmacology.

Irwin tests are key preclinical study elements for characterising drug-induced neurological side effects. This multicentre study aimed to assess the robustness of Irwin tests across multinational sites during three stages of protocol harmonisation. The projects were part of the Enhanced Quality in Preclinical Data framework, aiming to increase success rates in transition from preclinical testing to clinical application. Female and male NMRI mice were assigned to one of three groups (vehicle, MK-801 0.1and 0.3 mg kg-1). Irwin scores were assessed at baseline and multiple times following intraperitoneal injection of MK-801 using local protocols (Stage 1), shared protocols with harmonised environmental design (Stage 2) and fully harmonised Irwin scoring protocols (Stage 3). The analysis based on the four functional domains (motor, autonomic, sedation and excitation) revealed substantial data variability in Stages 1 and 2. Although there was still marked overall heterogeneity between sites in Stage 3 after complete harmonisation of the Irwin scoring scheme, heterogeneity was only moderate within functional domains. When comparing treatment groups versus vehicle, we found large effect sizes in the motor domain and subtle to moderate effects in the excitation-related and autonomic domains. The pronounced interlaboratory variability in Irwin datasets for the CNS-active compound MK-801 needs to be carefully considered when making decisions during drug development. While environmental and general study design had a minor impact, the study suggests that harmonisation of parameters and their scoring can limit variability and increase robustness.

The effect of L-carnitine in reactive oxygen species reduction and apoptotic gene expression in mice after cyclophosphamide: An experimental study.

Cyclophosphamide (CP), a utilized anticancer drug, is known to cause infertility in women. However, L-carnitine (LC), an antioxidant, has been shown to offer protective benefits against infertility. This study aimed to evaluate the levels of reactive oxygen species (ROS) and apoptotic gene expression in mice treated with CP and LC. 24 NMRI female mice (6-8 wk, 30 5 gr) were divided into 4 groups: control group: received normal saline intraperitoneal (IP) injection for 10 days; CP group: received 75 mg/kg of CP as a single IP on the 10 day of the experiment; LC group: received 200 mg/kg of LC IP for 10 days; LC+CP group: received LC for 10 days and CP single IP injection on the 10 day of the experiment. After 10 days, mice were superovulated. The oviducts were then removed, and the oocytes of each group were collected for evaluating apoptotic gene expression B-cell lymphoma 2(Bcl2), Bcl2-associated X(Bax), and Caspase3 via real-time polymerase chain reaction and intracellular ROS levels by dichloro-dihydro-fluorescein diacetate fluorescence staining. Data revealed that LC in the LC+CP group significantly increased Bcl2 gene expression (p = 0.01), and decreased Bax and Caspase3 gene expression compared to the CP group (p = 0.03, p = 0.04). LC decreased the ROS level in the LC+CP group compared to the CP group (p 0.001). Findings suggest that LC can scavenge the ROS caused by CP and modulate the apoptotic pathway via downregulating the Bax and Caspase3 genes and upregulating the Bcl2 gene in oocytes of mice exposed to CP.

The effect of vitamin C on the recovery of activity and survival of autografted ovaries through inhibition of oxidation and inflammation

Ovarian tissue autografting is a valuable clinical option to help restore fertility in women with cancer. However, many follicles are lost due to ischemia-reperfusion (IR) injury, which depletes follicles after grafting. We aimed to investigate the effect of vitamin C, an antioxidant with anti-apoptotic and anti-inflammatory properties, on improving the structure and function of autografted ovaries in mice. Thirty-six female NMRI mice (4–5 weeks old) were divided into three groups of 12: control (no grafting), autograft + vitamin C (50 mg/kg/day intraperitoneally), and autograft + saline (100 µl/day/animal, intraperitoneally). After the ovarian autografting and before the start of the experiment, each group was further divided into 7-day and 28-day subgroups. Seven days after ovary autografting, serum levels of malondialdehyde (MDA), total antioxidant capacity (TAC), and inflammatory factors were measured. On day 28, ovarian histology, DNA fragmentation, and estradiol and progesterone levels were assessed. Results were analyzed using one-way ANOVA and Tukey’s test, with significance set at p<0.05. In the autograft + vitamin C group, there were significant increases in the mean total volume of the ovary, cortex (p<0.05), medulla, number of follicles, and levels of IL-10, progesterone, estradiol, and TAC (p<0.001), compared to the autograft group. Conversely, the rate of apoptosis and serum levels of MDA, IL-6, and TNF-α were notably reduced in the autograft + vitamin C group (p<0.001). These results suggest that vitamin C can significantly enhance the recovery of autografted ovaries through its antioxidant, anti-inflammatory, and anti-apoptotic effects.

Effects of combination of melatonin and L-carnitine on in vitro maturation in mouse oocytes: An experimental study.

Melatonin and L-carnitine are free radical scavengers with antiapoptotic and antioxidant properties that improve oocyte development. This study aimed to find the possible effect of combining 2 antioxidant agents of melatonin and L-carnitine on oocyte morphology, maturation, apoptosis, and expression of bone morphogenetic protein 15 (BMP-15) and growth differentiation factor 9 (GDF-9) genes in a mice model. To overstimulation, 60 female NMRI mice were injected intraperitoneally using mare serum gonadotropin. On day 2 post-injection, 70 cumulus-oocyte complexes were collected from each mouse. The collected oocytes randomly were then divided into 4 groups including, the control, melatonin, L-carnitine, and melatonin + L-carnitine groups. The morphology and maturation rate of the oocytes was evaluated using a light microscope. Apoptosis was identified by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay and the expression of BMP-15 and growth and differentiation factor GDF-9 genes was also evaluated by real-time polymerase chain reaction. Oocyte diameter significantly was increased in combination treatment of L-carnitine and melatonin compared to other groups (p 0.05). L-carnitine group showed the highest mean percentage of oocyte cytoplasmic pattern. Results of the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling indicated that the lowest apoptosis rate belonged to the melatonin + L-carnitine group. Moreover, the combination groups showed the highest number of oocytes and maturation rate. The BMP-15 and GDF-9 genes were significantly upregulated in all treatment groups compared to the control group. Our results suggested a combination of melatonin + L-carnitine administration as a more effective choice for in vitro promotion of oocyte maturation.

Stereological and biochemical effects of thymoquinone on ovarian tissue toxicity induced by silver nanoparticles in NMRI mice: An experimental study.

The toxicity of silver nanoparticles (AgNPs) has been proven in the female reproductive system. Thymoquinone (TQ) is a natural antioxidant and bioactive component of Nigella sativa. We evaluated the efficacy of TQ on ovarian tissue following toxicity induced by AgNPs in female mice. 24 female NMRI mice (5-6 wk, an average weight of 33 gr) were randomly divided into 4 groups (n = 6/each): control, AgNPs (500 mg/kg, gavage), TQ (2.5 mg/kg, intraperitoneal injection), and TQ+AgNPs. Mice were treated every day for 35 days. Serum levels of malondialdehyde (MDA), total antioxidant capacity (TAC), luteinizing hormone, and follicle-stimulating hormone were measured. The optical disector and stereological techniques were utilized to estimate the follicular count, their volume at different developmental stages, and the structure of ovarian tissue. In the AgNPs group, the serum concentrations of TAC (p = 0.01), luteinizing hormone (p 0.001), follicle-stimulating hormone, the volume of corpus luteum (p 0.001), and the number of follicles decreased significantly compared to the control group. Nevertheless, AgNPs significantly increased the MDA level. In the TQ+AgNPs group compared to the AgNPs group, a significant decrease in MDA level (p 0.001) and a significant improvement in TAC (p = 0.03), and hormonal levels, the number of primary, preantral, and antral follicles (p = 0.04), and the volume of corpus luteum (p = 0.01) were observed. TQ improved the number of follicles by reducing oxidative stress and lipid peroxidation in AgNPs-damaged ovarian tissue.

Protective Effect of Bio-Scaffold Against Vitrification Damage in Mouse Ovarian Tissue.

Ovarian tissue cryopreservation is regarded as useful method for fertility preservation. This study aimed to preserve most of the follicular reserve from the destructive effects of cryoprotectant solutions and liquid nitrogen. For this purpose, 48 female NMRI mice (8 weeks old) were randomly divided into six groups: Fresh (not vitrified), Vitrification (not encapsulated), Alginate 1 (encapsulated in 1% alginate hydrogel before placing in vitrification solutions), Alginate 2 (encapsulated in 1% alginate hydrogel before placing in liquid nitrogen), Aloe vera 1 (encapsulated in Aloe vera pieces before placing in vitrification solutions), Aloe vera 2 (encapsulated in Aloe vera pieces before placing in liquid nitrogen). After vitrification and warming, the histological evaluation showed that the average number of intact primordial follicles decreased significantly in all groups compared to the Fresh group. (P < 0.05). Results of evaluating the expression of apoptosis-related genes showed that the ratio of Bax/Bcl2 and P53 significantly decreased in the Alginate 2 group compared with the vitrification group. The level of Kit gene (KIT proto-oncogeni receptor tyrosine kinase gene) expression was either the same or lower in the experimental groups than in the vitrification group, but there was no statistically significant difference. Levels of tissue nitric oxide (NO) and malondialdehyde (MDA) in Alginate groups 1 and 2 showed a significant decrease compared with the vitrification group (P < 0.05). To conclude, Encapsulation of ovaries in 1% alginate hydrogel before immersion in liquid nitrogen may reduce the damage caused by cryopreservation.

Angiogenic lipid-based drug delivery system (PhytoSolve) for treatment of a thin endometrium in animal model

Impaired vascular growth resulting from reduced vascular endothelial growth factor (VEGF) in the epithelial tissue of the glands is a primary cause of thin endometrium. Inducing angiogenesis offers a possible therapeutic strategy for this condition. This study aimed to develop a novel drug delivery system using S75 lipoid loaded with VEGF for thin endometrium therapy. The formulation of PhytoSolve consisted of a combination of lipid S75, glycerol, and MCT oil, which was prepared utilizing a probe sonicator. Female NMRI mice (n=30) were divided into six groups: control, sham, thin endometrial model, VEGF treatment, PhytoSolve treatment, and VEGF/PhytoSolve treatment. A thin endometrial model was induced by injecting 95 % ethanol. After the treatment period, tissue samples were collected to assess the endometrial thickness—the mean particle size of the PhytoSolve formulation measured 67.57±7.07 nm. Approximately 40 % of the loaded VEGF was released within the first 24 hours, followed by a sustained release rate of 10–20 % daily. The PhytoSolve group containing VEGF exhibited significantly increased endometrial thickness compared to the VEGF group (P<0.05). S75 lipoid-based PhytoSolve loaded with VEGF effectively promoted blood vessel formation. The combination of PhytoSolve S75 and VEGF holds promise for developing a biocompatible drug delivery system with therapeutic potential for treating thin endometrium and various other biomedical applications.

Effects of Ficus capensis Leaves Aqueous Extracts (Lactogenic Medicinal Plant) on NMRI Mice Milk Secretion

Introduction: Ficus capensis is a plant used in traditional medicine to stimulate lactation in women and animals in Africa. However, the effects of their extracts on the mammary gland are poorly documented. The objective of the study was to evaluate the effects of Ficus capensis leaves aqueous extracts on NMRI mice milk secretion. Methodology: This was an experimental animal study using virgin female NMRI mice aged eight to ten weeks. The mice were grouped into for groups of eight mice each. Each group received one of the following products: distilled water, Galactogil™, sulpiride, aqueous extracts (AE) of capensis leaves. Data were analysed and processed using Microsoft Excel 2016 and Stata MP 16 with P ≤ .05 as the significance threshold. Results: Arborescence of the galactophorous ducts was more developed in the sulpiride lot. Galactogil™, and capensis leaves extracts treated groups showed almost equivalent arborescence with a higher tendency than the distilled water. With histological haematin- eosin staining, the ratio of galactophorous ducts containing secretions to total ducts was higher in the groups of Ficus capensis AE treated group than distilled water (P = .0001). Galactogil™, sulpiride and the group of Ficus capensis extracts each had higher levels of beta-casein in mammary tissue and average prolactinemia than distilled water (P &lt; .01). Mammary tissue stained by immunohistochemistry with anti-prolactin receptor antibodies showed more intensely labelled mammary glands in the sulpiride and Ficus capensis extracts groups. There was no statistically significant difference between average progesteronemia among the different groups. Conclusion: F. capensis leaves AE administered to virgin female NMRI mice showed lactogenic and mammogenic effects. The extracts were able to increase the nutritional quality of the milk produced, as evidenced by the increase in protein secretion.

L-carnitine fails to rescue chemotherapy injured ovaries by epigenetic changes of transcription factors

Cyclophosphamide (CP), as an anti-cancer drug, is frequently used to treat various types of cancer. A decreased number of ovarian follicles impaired normal ovarian function, and subsequent premature ovarian failure (POF) presented as a side effect of cyclophosphamide usage. These events may eventually affect the fertility rate of individuals. The present study showed the effect of cyclophosphamide on ovarian reserves and the protective effect of L-carnitine (LC) as an antioxidant to prevent POF.To design the study, six to eight-week-old NMRI female mice were divided into three groups: control, cyclophosphamide (CP), and cyclophosphamide + L-carnitine (CP + LC). Mice received drugs intraperitoneally (IP) for 21 days. In the following 24 h after the last injection, both ovaries were used to evaluate the expression of Sohlh1 and Lhx8 genes by Real-time PCR. Furthermore, the alteration of Lhx8 promoter methylation was examined by Methylation-sensitive high-resolution melting analysis (MS-HRM).The present data showed the negative effect of CP on regulator genes of oogenesis including Sohlh1 and Lhx8. In addition, an examination of the epigenetic status of the Lhx8 gene showed a change in promoter methylation of this gene following cyclophosphamide injection. Although, L-carnitine is an effective antioxidant in relieving oxidative stress caused by cyclophosphamide and its damage, in the present study, however, the use of L-carnitine failed to protect the ovaries from changes caused by CP injection. So, using cyclophosphamide can alter the expression of folliculogenesis genes through its effects on epigenetic changes and may cause POF. The results of the present study showed that L-carnitine consumption can’t protect the ovaries against the adverse effects of CP.

All-trans retinoic acid and fibroblast growth factor-2 enhance the fertility rate and embryo development in polycystic ovary syndrome mouse model.

Polycystic ovary syndrome (PCOS) causes a developmental arrest of antral follicles and disrupts oocyte maturation. Retinoic acid (RA) and Fibroblast Growth Factor-2 (FGF2) are effective in follicle growth, thus their effects on histopathology and in vitro fertility of oocytes were investigated in PCOS-induced mice. Eighty female NMRI mice were randomly divided into 8 groups including 1-Normal mice, 2-PCOS mice without any treatment, 3-Normal mice treated with RA, 4-Normal mice treated with FGF2, 5-PCOS mice treated with RA, 6- PCOS mice treated with FGF2, 7- PCOS mice treated with RA and FGF2, and 8- Normal mice treated with RA and FGF2. Following PCOS induction, the mice were treated with intraperitoneal RA and FGF2 as a treatment. Then ovarian stimulation, for preparing the oocyte and embryo microscopic examinations was performed. After oocyte morphometry, through in vitro fertilization, the embryo formation was assessed. Data was analyzed by one-way ANOVA and Tukey tests. The results showed simultaneous injection of RA and FGF2 into PCOS-induced mice increases antral follicles and corpus luteum, but decreases cystic follicles. Simultaneous injection of these two substances into healthy mice increases the pre-antral follicles and corpus luteum. Simultaneous injection of RA and FGF2 increases the number of embryos in both control and intervention groups. It can be concluded that RA and FGF2 increase the maturity of ovarian follicles, the number of two-celled embryos, and the number of grade-A embryos in mice with PCOS, which is more effective when these two substances are injected simultaneously.

The Effect of The Conditioned Medium from Human Embryonic Stem Cells on Mouse Oocytes In Vitro Maturation.

Some reports have indicated that conditioned medium from growing mouse embryonic stem cells (ESCs) provides a supportive condition for small follicles growing, oocyte maturation, and following embryo growth. The aim of this study is assessing in vitro maturation (IVM) and consequent in vitro fertilization (IVF) outcome of immature mouse oocytes using human embryonic stem cells conditioned medium (HESCM). In this experimental study, 240 germinal vesicle (GV) oocytes were took from NMRI female mice, aged 4-6 weeks, 48 hours before injection of 5 IU pregnant mare serum gonadotropin (PMSG). 120 GV oocytes without cumulus cells were cultured in each of the groups. 120 GV were cultured in HESCM as test groups and also 120 GV cultured in human embryonic stem cells medium (HESM) as control groups. After evaluating the metaphase II (MII) oocyte maturation rate at 8, 16 and 24 hours, the MII oocytes subsequently were fertilized in vitro and the two-cell embryo development rate was recorded at days 1, 2, and 3. Statistical analysis was performed by using the generalized estimating equations (GEE) method that calculated their rate ratio. Our data indicated there are significant differences between the maturation rates in HESCM and HESM (P=0.004), also the two-cell embryo development was significant between two culture media (P=0.00). Similar to some other studies, the secretome of the HESCM showed a significant impact on the IVM outcomes in mice.

Maternal music exposure during pregnancy influences reflexive motor behaviors in mice offspring.

Evidence supports that music can modulate many physiological roles, exerting clear effects on the central nervous system. For this effect to be positive, music should be tuned at a frequency of 432 Hz. This study aims to determine the effects of prenatal exposure to music on reflexive motor behaviors in mice offspring. Six pregnant female NMRI mice (8-10weeks old) were randomly and equally allocated into two groups. Group 1 as control was placed in a normal housing area (average room noise 35 dB), and Group 2 was exposed to music pitched at 432 Hz for 2h a day played at constant volume (75/80 dB) during pregnancy. Following delivery, four pups from each pregnant mouse were selected, and reflexive motor behaviors including ambulation, hind-limb foot angle, surface righting, grip strength, front- and hind-limb suspension, and negative geotaxis were determined. Based on the findings, prenatal exposure to music significantly increased ambulation score, grip strength, and front- and hind-limb suspension compared to the control group (P< 0.05). Also, prenatal exposure to music significantly decreased hind-limb foot angle, negative geotaxis, and surface righting compared to the control group (P< 0.05). These results suggested that music exposure during pregnancy had a significant positive effect on all tested reflexive motor behaviors in mice offspring.

Maternal supplementation of L-carnosine improves reflexive motor behaviors in mice offspring

This study aimed to investigate the effect of maternal supplementation of L-carnosine on improved reflexive motor behaviors in mice offspring. Forty pregnant female NMRI mice were allocated into four groups. In the control group, mice received water, while in groups 2–4, female mice received supplementation of the L-carnosine (0.001, 0.01, or 0.1 mg/kg) at gestation days (G.D.) 5, 8, 11, 14, and 17. Newborn male pups were selected, and reflexive motor behaviors were analyzed on days 5, 7, 10, and 10‐15, respectively. Serum malondialdehyde(MDA), superoxide dismutase(SOD), glutathione peroxidase(GPx) and total antioxidant status(TAS) of was determined in offspring’s. According to findings, prenatal supplementation of the L-carnosine significantly increased ambulation score, surface righting, hind-limb suspension score, grip strength, front-limb suspension time, and negative geotaxis in mice offspring (P < 0.05). Hind-limb foot angle decreased in mice offspring by maternal supplementation of the L-carnosine (P < 0.05). Prenatal supplementation of the L-carnosine significantly decreased the MDA and increased the SOD, GPx, and TAS levels in offspring (P < 0.05). These results suggested maternal supplementation of the L-carnosine improved reflexive motor behaviors and antioxidant status in mice offspring.

Effects of cigarette smoke condensate on reproduction in mice in vivo

Smoking has dangerous and sometimes irreversible effects on various body tissues, including the reproductive system. We conducted this research to determine the in vivo effects of cigarette smoke condensate (CSC) on reproduction in mice. In this experimental in vivo study, 32 male and female NMRI mice were divided into four groups. The mice were injected with CSC (CSC-1R3F) for 28 days. The mice were mated 1 day after the last injection and observed daily for 1 week for the presence of a vaginal plug to track mating. We evaluated mating success rate, and sperm and oocyte quality, pregnancy outcome, childbearing status, and in vitro fertilization (IVF). The results showed a decrease in successful mating in female mice that received the CSC injections. CSC significantly influenced the number of offspring born to males. When the CSC was injected into male mice, there was a significant increase in the number of offspring compared with the group in which only the females received CSC injections. According to the results, there was a negative effect of CSC on morphological parameters in male and female mice. Also, successful IVF after exposure to CSC was significantly decreased in the female mice treated group. The results indicated that CSC significantly affected the number of offspring and fecundity success in females.

Effects of pulsed electromagnetic fields and N-acetylcysteine on transplantation of vitrified mouse ovarian tissue

ABSTRACT In this experimental study, adult female NMRI mice were randomly assigned to five groups: control ;(fresh ovarian transplantation, OT); sham ;(vitrified OT); NAC ;(vitrified OT treated with N-acetyl cysteine, NAC); EMF ;(vitrified OT treated with pulsed electromagnetic fields, PEMF); and NAC+EMF ;(vitrified OT combined with NAC and PEMF). We conducted histological assessments to evaluate follicle reservation and vascularization. Furthermore, we examined the relative expression of Fgf-2, Vegf, Tnf-α, Il-6, Il-1, and Cd31 genes on days 2 and 7 after OT. Additionally, we measured total antioxidant capacity (TAC), malondialdehyde (MDA) levels, as well as the activity of superoxide dismutase (SOD) and glutathione peroxidase (GPX). Our results demonstrated that NAC, PEMF, and NAC+PEMF treatments significantly increased the number of follicles. Moreover, we observed a more pronounced development of vascularization in the NAC, PEMF, and PEMF+NAC groups. The relative expression levels of Fgf-2, Vegf, Tnf-α, Il-1β, and Il-6 were significantly elevated in the NAC, PEMF, and NAC+PEMF groups. Notably, TAC levels decreased significantly in the NAC group compared to the control group. Additionally, the MDA level showed a significant decrease in the PEMF+NAC group when compared to the other groups. Overall, the combination of NAC and PEMF exhibited a synergistic effect in promoting angiogenesis and protecting against oxidative stress and inflammation during OT.

Insulin Ameliorates Folliculogenesis in An Experimental Model of PCOS Mice.

Insulin is an essential factor that controls female reproductive system. Insulin signaling via Foxo1 and Akt1 can improve steroidogenesis, cell proliferation, and protein synthesis. We aimed to determine the effect of insulin on possible changes in gene expression, hormonal status, and histological aspects of the ovary following the induction of the animal model of polycystic ovary syndrome (PCOS). In this experimental study, 24 adult female NMRI mice weighing 25-30 g were randomly placed in three groups: control, PCOS (60 mg/kg dehydroepiandrosterone (DHEA) for 20 days, and PCOS+insulin (60 mg/kg DHEA for 20 days+100 μL insulin diluted in water twice a week for 30 consecutive days). Blood specimens were obtained from the heart and the serum levels of testosterone, progesterone, and estradiol were measured. Right, and left ovaries were removed for real-time polymerase chain reaction (PCR) and stereological study. DHEA injection significantly amplified the concentration of testosterone, progesterone, and estradiol. While insulin treatment amended the level of reproductive hormones. DHEA injection significantly reduced the expression levels of Irs1-4, Pdk1, Pi3k, and Akt1-3 and raised the expression level of Caspase-3. However, insulin administration amplified expression levels of Irs1-4, Pdk1, Pi3k, and Akt1-3, and reduced Caspase-3. The total volume of ovarian tissue in mice receiving DHEA significantly declined compared to the control group. Besides, a substantial decrease was detected in the number of ovarian antral, Graafian, and primordial follicles and also in the total number of corpus luteum following DHEA administration. Comparison of structural alterations in ovarian tissue between the PCOS+insulin and the PCOS groups displayed that insulin administration improved the total number of Graafian, primordial, and antral follicles and also corpus luteum. In general, short-term insulin treatment showed improvement in hormonal balance, folliculogenesis, and insulin resistance in the ovaries of the PCOS mice model.

Effect of Taurine and Curcumin on In-Vitro Fertilization in NMRI Mice Treated with Acrylamide

Introduction: The aim of this study was to evaluate the effect of taurine and curcumin on in vitro fertilization (IVF) in female mice treated with acrylamideand and its effect on malondialdehyde (MDA) concentration and total antioxidant capacity (TAC).&#x0D; Methods: A total of 48 adult female NMRI mice were randomly divided into 6 groups, including control, curcumin 200 mg / kg, taurine 150 mg / kg, acrylamide 5 mg / kg, acrylamide 5 mg / kg + curcumin 100 and 200, acrylamide 5 mg / kg + Taurine 75 and 150 mg / kg. The drugs were administered orally for 35 days, and then IVF rate, MDA and TAC concentrations were examined in each group. &#x0D; Results: The results showed a significant decrease in oocyte, fertilization percentage, 2, 4 and 8 cell, Compact and blastocytes embryos in the acrylamide group compared to the control (P&lt;0.05). In acrylamide group, MDA concentration increased and TAC showed a significant decrease compared to other groups (P&lt;0.05). There was a significant increase in oocyte count and fertilization percentage in taurine group compared to the control (P‌&lt;0.001). A significant increase in the above parameters was observed in the acrylamide + taurine group at a dose of 150 mg / kg compared to the acrylamide group (P&lt;0.05). Percentage of fertilization and embryos of 2, 4 and 8 cells, Compact and blastocytes in the curcumin group showed a significant decrease compared to the control (P&lt;0.05).&#x0D; Conclusion: The results indicate that taurine has a better performance in reducing the side effects of acrylamide than curcumin. Since curcumin can prevent IVF, it should be used with more caution at the beginning of pregnancy.

Sex-Specific Modulation of the Host Transcriptome in the Spleen of Schistosoma mansoni-Infected Mice.

BackgroundSchistosomiasis is a severe parasitic disease that is primarily driven by the host’s immune response to schistosome eggs trapped in tissue and by the granulomatous inflammatory and fibrotic reaction they cause. Despite significant progress in understanding the complex immunological processes involved in the relationship between schistosomes and their host, neither an effective vaccine against the infection nor anti-fibrotic drugs currently exists, making the search for new targets for schistosome drugs and vaccine candidates even more important. In order to identify new molecular targets for defense against or elimination of the parasite, we investigate herein the interplay between the host and male or female schistosomes, clearly separating this from the action of the parasite eggs.MethodsFor this purpose, we infected 6–8-week-old female NMRI mice with 100 male (M), female (F), or both (MF) S. mansoni cercariae and performed a comparative transcriptomic and flow cytometric analysis of their spleens.ResultsPrincipal component analysis of a total of 22,207 transcripts showed a clear clustering of the experimental groups. We identified a total of 1,293 genes in group M, 512 genes in group F, and 4,062 genes in group MF that were differentially expressed compared to naive controls. The highest percentage of regulated genes (2,972; 65.9%) was found in group MF alone, but there was a large overlap between groups M and MF (798; 17.7%) and a small overlap between groups F and MF (91; 2.0%). Only 4.5% of genes (201) were revealed to be regulated in all experimental groups (M/F/MF). In addition, we were able to show that both worm sexes trigger immune responses in an egg-independent manner (non-polarized Th1 and Th2 response), with female worms exerting less regulatory influence than males.ConclusionOur data show that adult schistosomes trigger sex-specific, egg-independent immune responses. The lists of genes regulated by adult female or male worms presented here may be useful in deciphering host–parasite interactions to identify targets for schistosome elimination.

Insulin improves ovarian function during the ovarian cycle in adult mice

Folliculogenesis is controlled by numerous inside and outside ovarian factors such as endocrine, paracrine, and autocrine signals. Among these factors, insulin is an important molecule that regulates processes in the female reproductive system. So, the purpose of this study was to determine the impact of insulin treatment on ovary tissue during the ovarian cycle. For this probe, 18 adult female NMRI mice were randomly divided into two groups: control and insulin (100 μL with a 72-hour interval by intraperitoneal injection for 30 days). Blood samples for hormonal evaluation were obtained from the heart, and the serum levels of FSH, LH, progesterone, and estradiol were measured. Then, right and left ovaries were extracted for real-time PCR and stereology, respectively. According to our results, insulin administration increased mRNA levels of INS-R, Ki67, while reduced Caspase-3, IGF-1, and FOXO-1. Insulin administration augmented the concentrations of female reproductive hormones. Histological analyses showed that the total volume of ovary in mice receiving insulin was significantly reduced. Likewise, a significant decrease in the number of antral follicles, Graafian follicles, and the number of corpora lutea were seen following the use of insulin. In contrast, the results showed a significant growth in the number of primordial and primary follicles in the insulin group compared with the control group. Briefly, insulin administration is able to increase the expression of genes related to insulin receptor and cell proliferation, as well as the amount of female reproductive hormones, but simultaneously, has a dual effect on the histological parameters of the ovary.