Performance Of Female Mice Research Articles

Caveolin-3 regulates slow oxidative myofiber formation in female mice

Abstract Objectives Caveolin-3 (Cav-3) plays a pivotal role in maintaining skeletal muscle mass and function. Mutations or deletions of Cav-3 can result in the development of various forms of myopathy, which affect the integrity and repair capacity of muscle fiber membranes. However, the potential effect of Cav-3 on myofiber type composition remains unclear. Methods To investigate the effect of Cav-3 on muscle strength and running capacity, we examined the grip force test and the low/high-speed running test. Oxidative and glycolytic myofiber-related genes, proteins, and skeletal muscle fiber composition were measured to determine the role of the Cav-3 in oxidative myofiber formation. Results We report the impact of Cav-3 on enhancing muscle endurance performance in female mice, and the discovery of a new physiological function to increase the proportion of slow-twitch oxidative muscle fiber by analyzing the gastrocnemius and soleus. Skeletal muscle-specific ablation of Cav-3 in female mice increased oxidative myofiber-related gene expression and type I oxidative myofiber composition, with resultant improvements in endurance performance. In male mice, the absence of Cav-3 in skeletal muscle reduced in the expression of glycolytic fiber-related genes and proteins. Conclusions This study identified Cav-3 as a regulator of slow-twitch oxidative muscle fiber formation acting on female mice, which may provide a potential target for improving muscle oxidative function.

Self-triggered thermoelectric nanoheterojunction for cancer catalytic and immunotherapy

The exogenous excitation requirement and electron-hole recombination are the key elements limiting the application of catalytic therapies. Here a tumor microenvironment (TME)-specific self-triggered thermoelectric nanoheterojunction (Bi0.5Sb1.5Te3/CaO2 nanosheets, BST/CaO2 NSs) with self-built-in electric field facilitated charge separation is fabricated. Upon exposure to TME, the CaO2 coating undergoes rapid hydrolysis, releasing Ca2+, H2O2, and heat. The resulting temperature difference on the BST NSs initiates a thermoelectric effect, driving reactive oxygen species production. H2O2 not only serves as a substrate supplement for ROS generation but also dysregulates Ca2+ channels, preventing Ca2+ efflux. This further exacerbates calcium overload-mediated therapy. Additionally, Ca2+ promotes DC maturation and tumor antigen presentation, facilitating immunotherapy. It is worth noting that the CaO2 NP coating hydrolyzes very slowly in normal cells, releasing Ca2+ and O2 without causing any adverse effects. Tumor-specific self-triggered thermoelectric nanoheterojunction combined catalytic therapy, ion interference therapy, and immunotherapy exhibit excellent antitumor performance in female mice.

Roxadustat enhances exercise performance in female mice

Roxadustat enhances exercise performance in female mice

The Effects of Fasting or Ketogenic Diet on Endurance Exercise Performance and Metabolism in Female Mice.

The promotion of ketone body (KB) metabolism via ketosis has been suggested as a strategy to increase exercise performance. However, studies in humans and animals have yielded inconsistent results. The purpose of the current study was to examine the effects of ketosis, achieved via fasting or a short-term ketogenic diet (KD), on endurance exercise performance in female mice. After 8 h of fasting, serum KB significantly increased and serum glucose significantly decreased in fasted compared to fed mice. When subjected to an endurance exercise capacity (EEC) test on a motorized treadmill, both fed and fasted mice showed similar EEC performance. A 5-week KD (90% calories from fat) significantly increased serum KB but did not increase EEC times compared to chow-fed mice. KD mice gained significantly more weight than chow-fed mice and had greater adipose tissue mass. Biochemical tissue analysis showed that KD led to significant increases in triglyceride content in the heart and liver and significant decreases in glycogen content in the muscle and liver. Furthermore, KD downregulated genes involved in glucose and KB oxidation and upregulated genes involved in lipid metabolism in the heart. These findings suggest that a short-term KD is not an effective strategy to enhance exercise performance and may lead to increased adiposity, abnormal endogenous tissue storage, and cardiometabolic remodeling.

The Nest Building Test in Mice for Assessment of General Well-Being.

This chapter presents a method for assessing general behavior, well-being, and sensorimotor gating. A detailed protocol is given for assessment of nest building performance in female mice using a strict scoring system. The test can be used for assessing moods and behaviors associated with psychiatric disorders such as depression and schizophrenia. It can also be useful for testing movement disorders such as Parkinson disease.

Female Reproductive Performance in the Mouse: Effect of Oral Melatonin.

Although melatonin has some of the broadest ranges of actions on the physiology of vertebrates, especially on their reproductive processes, the mechanism by which melatonin regulates animal reproduction is still incompletely understood. This study was designed to determine the effect of oral melatonin on the reproductive performance of female mice. Female ICR mice (7 weeks old) were given melatonin-containing water (3, 30 and 300 μg/mL; melatonin) or water only (control) until 10 weeks of age. Then, some of the mice were successfully mated (confirmed by vaginal plugs), and the number of live births and their weights were recorded. Some mice were used for a histological analysis of the number of follicles in the ovaries. Others were used for oocyte collection after superovulation, and in vitro fertilization (IVF) was performed. The mRNA expression of the apopotosis-related genes (BAX, BCL2) in the IVF embryos were analyzed. After melatonin administration, the mice showed similar serum melatonin levels to that of the control. The number of antral follicles per mm2 unit area in the 30 μg/mL melatonin-treated group (14.60) was significantly higher than that of the control (7.78), which was lower than that of the 3 μg/mL melatonin-treated group (12.29). The litter size was significantly higher in the 3 μg/mL melatonin-treated group (15.5) than in the control (14.3). After IVF, the hatched blastocyst formation rate in the 30 μg/mL melatonin-treated group (85.70%) was significantly higher than that of the control (72.10%), and it was the same for the BCL2/BAX expression ratio. Although oral melatonin did not appear to have an effect on the serum melatonin rhythm in the mouse, melatonin did increase litter size at the 3 μg/mL dose level, and improved the developmental competency of IVF embryos at the 30 μg/mL level.

Mechanisms of Gender Differences in Exercise Capacity

The examination of gender differences has been a recent priority of the NIH. It is well documented that female rodents exhibit higher exercise capacity than their male counterparts. We confirmed this in C57 wild‐type(WT) mice, where female mice exhibited greater, p<0.05, maximal exercise capacity for running distance (469 ± 24 m) than age‐matched male WT mice (337 ± 14 m). The first goal was to examine whether these differences persisted with models of enhanced exercise capacity, e.g. exercise training and the adenylyl cyclase type 5 knockout (AC5 KO) mouse. When WT mice underwent chronic exercise‐training, female mice maintained their superiority over males, with females running a 32% greater distance (p<0.05) than age‐matched trained males. However, AC5 KO mice, which demonstrated enhanced exercise capacity, did not exhibit a gender difference, with female AC5 KO mice (695 ± 51 m) running similar distances to male AC5 KO mice (661 ± 45 m). The next goal was to determine mechanisms mediating these differences. After ovariectomy, WT female mice no longer demonstrated enhanced exercise compared with males. Conversely, chronic administration of estrogen to male mice improved their exercise performance and eliminated the gender differences with exercise. Next we investigated nitric oxide (NO), a downstream target of estrogen. Total NO synthase (NOS) activity was higher in female mice compared with male mice in both sedentary (207 ± 14 U/mg vs. 138 ± 4 U/mg, p<0.05) and exercise trained groups (338 ± 42 vs. 193 ± 15 U/mg, p<0.05). Ovariectomized females exhibited nitric oxide levels similar to males (165 ± 11 U/mg). Administration of L‐NAME, resulting in NO blockade, eliminated the gender differences in exercise performance. In AC5 KO mice NOS activity was not different in male and female mice and similar exercise performance in males and females was still observed after treatment with L‐NAME. Thus, both estrogen and nitric oxide are key mechanisms mediating the enhanced exercise performance in female mice.Support or Funding InformationThis study was supported by the National Institute of Health grant R01HL106511This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Resveratrol protects against age-associated infertility in mice

Does resveratrol counteract age-associated infertility in a mouse model of reproductive aging? Long-term-oral administration of resveratrol protects against the reduction of fertility with reproductive aging in mice. Loss of oocytes and follicles and reduced oocyte quality contribute to age-associated ovarian aging and infertility. Accumulation of free radicals with age leads to DNA mutations, protein damage, telomere shortening, apoptosis and accelerated ovarian aging. Increasing evidence shows that resveratrol, enriched in certain foods, for example red grapes and wine, has anti-tumor and anti-aging effects on somatic tissues by influencing various signaling pathways, including anti-oxidation, as well as activating Sirt1 and telomerase. We investigated the potential of resveratrol to stave off ovarian aging in the inbred C57/BL6 mouse model. Young C57/BL6 females (aged 2-3 months) were fed with resveratrol added to drinking water at 30 mg/l (providing ∼7.0 mg/kg/day) for 6 or 12 months, and the fertility and ovarian functions were compared among mice treated with or without resveratrol, and young mice served as reproductive controls. Experiments were repeated three times, with an average of 25 females randomly allocated to each treatment group for each repeat. Reproductive performance of female mice was determined by litter size, ovarian follicles and oocyte quantity and quality, and compared with age-matched controls. The impact of resveratrol on telomeres and telomerase activity, and expression of genes associated with cell senescence also was evaluated. Young mice fed with resveratrol for 12 months retained the capacity to reproduce, while age-matched controls produced no pups. Consistently, mice fed with resveratrol for 12 months exhibited a larger follicle pool than controls (P < 0.05). Furthermore, telomerase activity, telomere length and age-related gene expression in ovaries of mice fed with resveratrol resembled those of young mice, but differed (P < 0.05) from those of age-matched old mice. Resveratrol improved (P < 0.05) the number and quality of oocytes, as evidenced by spindle morphology and chromosome alignment. Also, resveratrol affected embryo development in vitro in a dose-dependent manner. The doses of resveratrol and the experimental conditions used by different research groups have varied considerably, and the dosage influences both the effectiveness and toxicity of resveratrol. Fine-tuning the dosage of resveratrol likely will optimize its anti-aging effects on ovarian function. Our data provide a proof of principle of the fertility-sparing effect of resveratrol in female mice. Although depletion of the ovarian reserve of high-quality oocytes also contributes to increased infertility with reproductive aging in women, the data obtained using a mouse model may not extrapolate directly to human reproduction, and more extensive research is needed if any clinic trials are to be attempted. This work was supported by MOST of China National Basic Research Program (grant number: 2010CB94500 and 2012CB911200). The authors have no competing interests to declare.

Effects of immunization against a DNA vaccine encoding somatostatin gene (pGM-CSF/SS) by attenuated Salmonella typhimurium on growth, reproduction and lactation in female mice

A novel somatostatin (SS) DNA vaccine (pGM-CSF/SS), delivered orally by attenuated Salmonella typhimurium (CSO22), was used to immunize female mice at 5, 7, and 11 wk of age; the objective was to investigate the humoral immune response and effects of this vaccine on growth, reproduction and lactation. The pGM-CSF/SS induced SS-specific antibodies, which peaked (3.69 ± 0.89; mean ± S.D) 4 wk after the first booster immunization. Compared with a saline-treated control group, body weight gain of a pGM-CSF/SS immunized group increased 30.3% (23.88 vs. 18.32 g, P < 0.05) during the growth period (from 2 wk after primary immunization to 4 wk after the first booster immunization). Immunized mice had higher plasma estradiol concentrations (84.10 ± 2.16 vs. 81.45 ± 2.12 pg/ml, P < 0.05) and a shorter estrous cycle (4.06 ± 0.75 vs. 5.33 ± 0.49 d, P < 0.05), but serum progesterone concentrations were not significantly affected. Since offspring produced by immunized mice gained weight faster (P < 0.05) in the first 2 wk of life (4.27 ± 0.62 and 7.81 ± 1.30 g in Weeks 1 and 2, respectively vs. 3.70 ± 0.23 and 7.14 ± 0.48 g), we inferred that pGM-CSF/SS could have a direct or indirect role in regulating lactation in mice. In conclusion, GM-CSF and CSO22 served as adjuvant and attenuated live vector, respectively, with efficient oral delivery of an SS DNA vaccine which successfully induced a humoral immune response and enhanced rate of weight gain. Furthermore, the DNA vaccine pGM-CSF/SS affected plasma estradiol concentrations and the estrous cycle, and seemed to enhance lactation performance of female mice.

Identification of Genetic Regions of Importance for Reproductive Performance in Female Mice

Both environmental and genetic factors can dramatically affect reproductive performance in mice. In this study we have focused on the identification of genetic regions, quantitative trait loci (QTL), which affect the breeding capacity of female mice. We have identified polymorphic microsatellite markers for the mouse strains used and performed a genomewide scan on 237 females from a gene-segregating backcross between a high breeder and a relatively poor breeder. The high-breeder mouse strain we used is the inbred NFR/N mouse (MHC haplotype H-2q), which has extraordinary good breeding properties. The moderate breeder chosen for F(1) and N2 progeny was B10.Q, which is a genetically well-characterized MHC-congenic mouse of the H-2q haplotype. Each of the 237 females of the N2 generation was allowed to mate twice with MHC-congenic B10.RIII (H-2r) males and twice with B10.Q males. A predetermined number of phenotypes related to reproductive performance were recorded, and these included litter size, neonatal growth, and pregnancy rate. Loci controlling litter size were detected on chromosomes 1 (Fecq3) and 9 (Fecq4). The neonatal growth phenotype was affected by Fecq3 and a locus on chromosome 9 (Neogq1). On chromosome 11 two loci affecting the pregnancy rate (Pregq1 and Pregq2) were identified. Furthermore, on chromosomes 13 and 17 we found loci (Pregq3 and Pregq4) influencing the outcome of allogeneic pregnancy (allogeneic by means of MHC disparity between mother and fetuses). A locus on chromosome 1 affecting maternal body weight was also identified and has been denoted Bwq7. It is well known that reproductive performance is polygenically controlled, and the identification of the major loci in this complex process opens the possibility of investigating the natural genetic control of reproduction.

Effect of delayed breeding on the reproductive performance of female mice.

The aim of the present study was to determine, in the mouse, whether maintaining females as virgins until an advanced reproductive age was associated with decreased reproductive performance and reproductive lifespan compared with females of the same age that were first mated with males at an earlier reproductive age. Randomly selected virgin hybrid (C57BL/6JIco female x CBA/JIco male) female mice were housed individually with a randomly selected 12- to 14-week-old hybrid male either at the age of 28 weeks (normal breeding group; n = 20) or 51 weeks (delayed breeding group; n = 23) for the rest of their reproductive life. Females were checked once daily to determine the day of parturition and to record the litter size and gender of pups at birth for each consecutive litter. At weaning, offspring were weighed and killed. Delayed breeding was associated with smaller litter sizes, both at birth and at weaning, a higher bodyweight of pups at weaning, a higher percentage of litters with at least one newborn pup cannibalised, earlier cessation of female reproductive life and a higher mortality rate of dams during the breeding period. These results show that delayed breeding in the mouse is associated with decreased reproductive performance and a shorter reproductive lifespan compared with females bred at an earlier reproductive age.

Effect of delayed breeding on the reproductive performance of female mice

The aim of the present study was to determine, in the mouse, whether maintaining females as virgins until an advanced reproductive age was associated with decreased reproductive performance and reproductive lifespan compared with females of the same age that were first mated with males at an earlier reproductive age. Randomly selected virgin hybrid (C57BL/6JIco female × CBA/JIco male) female mice were housed individually with a randomly selected 12- to 14-week-old hybrid male either at the age of 28 weeks (normal breeding group; n = 20) or 51 weeks (delayed breeding group; n = 23) for the rest of their reproductive life. Females were checked once daily to determine the day of parturition and to record the litter size and gender of pups at birth for each consecutive litter. At weaning, offspring were weighed and killed. Delayed breeding was associated with smaller litter sizes, both at birth and at weaning, a higher bodyweight of pups at weaning, a higher percentage of litters with at least one newborn pup cannibalised, earlier cessation of female reproductive life and a higher mortality rate of dams during the breeding period. These results show that delayed breeding in the mouse is associated with decreased reproductive performance and a shorter reproductive lifespan compared with females bred at an earlier reproductive age.

Influence of sulfate in drinking water on mouse reproduction during two parities.

Field studies have suggested that high levels of sulfate in drinking water may alter water consumption and have an adverse effect on animal reproduction. This study was conducted to determine whether sulfate in the drinking water affects the reproductive performance of female mice during gestation and lactation over two parities. Sixty random-bred albino mice were randomly assigned to six sulfate treatments. Sodium sulfate was added to deionized distilled water to give sulfate levels in ppm as follows: (1) 0 (control); (2) 0 (Na control); (3) 625; (4) 1,250; (5) 2,500 and (6) 5,000. Treatments 2 to 6 contained the same Na content (2,392 ppm) by varying Na bicarbonate content. Mice receiving only the deionized distilled water drank less (P less than .05) than mice receiving the other treatments at all times measured. Animals offered the 0 (Na control) water drank more (P less than .05) water than mice on the other sulfate treatments. There was no difference (P greater than .10) in litter size, litter weaning weight, or gestational and lactational weight gain of the dam among water treatments. Although levels of sulfate up to 5,000 ppm and 2,392 ppm Na in the drinking water cubicly altered water consumption, they did not affect litter size, litter weaning weight, or gestational and lactational weight gain of the dam when sulfate ingestion was continued over two parities.

Comparative Effects of Protracted Exposures to60Co γ-radiation and239Pu α-radiation on Breeding Performance in Female Mice

Breeding performances are compared of hybrid female mice given 239Pu (5 or 10 mu Cikg-1 body mass in 1% trisodium citrate via the tail-vein), or kept in a 10 rad/day or 20 rad/day 60Co gamma-irradiation field (but mated in the control area), or unirradiated. Ovarian dose-rates from the injected plutonium were initially 0.8 and 1.7 rad/day, changing little thereafter; actual gamma-ray dose-rates to breeding females averaged around 8 and 16 rad/day respectively. Both gamma-ray treatments affected reproductive performance more than the plutonium injections, with respet to duration of fertility and to offspring per litter in successive 4-weekly periods, though overall mean litter-sizes were not significantly less than controls. The r.b.e. for these effects on reproduction, attributed to germ-cell killing, is about 2.5 for the alpha-particles vs. gamma-rays, lower than for testis mass reduction in males. This low r.b.e. may be connected with inhomogeneity of alpha-particle dose within the ovary, but it is known that fission neutron versus gamma r.b.e.'s for impairment of female fertility are also lower than those for impairment of male fertility.