Juvenile Female Mice Research Articles

Histopathological effects on target organ maturation in juvenile female mice upon exposure to 2,3,7,8-TCDD, PCB-153, PBDE-47 or HBCD through a salmon-based diet

Histopathological effects on target organ maturation in juvenile female mice upon exposure to 2,3,7,8-TCDD, PCB-153, PBDE-47 or HBCD through a salmon-based diet

Exposure of juvenile female mice to isoflavone causes lowered expression of estrogen-related receptor gamma gene in vagina

In our previous study, the vaginal opening (VO) day of C57BL/6 mice was accelerated several days by chronic exposure to a 0.05% isoflavone (IF) fortified diet. The purpose of this study was to investigate whether the acceleration of VO by IF (1) has a critical window, (2) is modified by IF exposure combined with 17β-estradiol (E2), and (3) has any relation with gene expressions of estrogen-related receptors (ERRs). As a result, we determined that the critical window for the acceleration of VO was between 15 and 21 days postnatal. The combined effect of E2 and IF was thought to be additional in the acceleration of VO. The gene expression of ERRγ was significantly decreased in vagina by IF. The reduction of ERRγ may have two possible sequelae: disarrangement of vaginal development and high risk of vaginal cancer. In conclusion, IF exposure has a critical window for acceleration of VO and may have adverse effect on mouse vagina.

Age- and region-specific imbalances of basal amino acids and monoamine metabolism in limbic regions of female Fmr1 knock-out mice

The Fragile X syndrome, a common form of mental retardation in humans, originates from the loss of expression of the Fragile X mental retardation gene leading to the absence of the encoded Fragile X mental retardation protein 1 (FMRP). A broad pattern of morphological and behavioral abnormalities is well described for affected humans as well as Fmr1 knock-out mice, a transgenic animal model for the human Fragile X syndrome. In the present study, we examined neurochemical differences between female Fmr1 knock-out and wildtype mice with particular focus on neurotransmission. Significant age- and region-specific differences of basal tissue neurotransmitter and metabolite levels measured by high performance liquid chromatography were found. Those differences were more numerous in juvenile animals (postnatal day (PND) 28–31) compared to adults (postnatal day 209–221). In juvenile female knock-out mice, especially aspartate and taurine were increased in cortical regions, striatum, cerebellum, and brainstem. Furthermore, compared to the wildtype animals, the juvenile knock-out mice displayed an increased level of neuronal inhibition in the hippocampus and brainstem reflected by decreased ratios of (aspartate+glutamate)/(taurine+GABA), as well as an increased dopamine (DA) turnover in cortical regions, striatum, and hippocampus. These results provide the first evidence that the lack of FMRP expression in female Fmr1 knock-out mice is accompanied by age-dependent, region-specific alterations in brain amino acids, and monoamine turnover, which might be related to the reported synaptical and behavioural alterations in these animals.

Galanin synaptic input to gonadotropin-releasing hormone perikarya in juvenile and adult female mice: implications for sexual maturity

Changes in connectivity of the gonadotropin-releasing hormone (GnRH) neuronal system are believed to occur during the transition from juvenile to adulthood in females. Experiments were designed to investigate whether there is any difference in the number of galanin inputs to GnRH cells located in the organum vasculosum of lamina terminalis-rostral preoptic area (OVLT-rPOA) between juvenile (2 weeks old) and adult (10 weeks old) female mice. Triple label immunofluorescence staining of brain sections for galanin, GnRH and the presynaptic vesicle marker synaptophysin coupled with confocal microscopy was employed to identify galanin synapses to GnRH perikarya. The number of galanin synapses to GnRH cells and the proportion of GnRH cells with galanin input were significantly higher in adults than in juvenile mice. In adult mice, the proportions of GnRH cells with 0, 1, 2, 3, 4, 5 or 6 galanin synapses/cell were comparable to each other whereas in the juveniles the vast majority of them received no galanin synaptic input. A greater number of galanin synapses in adult as compared with juvenile female mice suggests a functional role for galanin in the maturation of the GnRH system.

Direct regulation of postnatal GnRH neurons by the progesterone derivative allopregnanolone in the mouse.

The mechanisms through which gonadal steroids exert critical feedback actions upon the activity of the GnRH neurons are not understood. We have examined here whether progesterone may modulate the electrical activity of the GnRH neurons following its rapid metabolism to the neuroactive steroid allopregnanolone within the brain. Using an acute brain slice preparation, whole-cell, patch-clamp recordings were made from GnRH neurons of juvenile (postnatal d 15-20) and adult (postnatal d 60-70) female mice in the presence of tetrodotoxin. Progesterone (1 microM) was not observed to have any actions (up to 5 min exposure) upon GnRH neurons. However, allopregnanolone (500 nM-1 microM) exerted rapid (<1 min) effects upon the baseline membrane potential of all GnRH neurons and also significantly (P < 0.01) enhanced their GABA responses by up to 4-fold. All GABA and allopregnanolone responses were abolished by the GABA(A) receptor antagonist bicuculline. No differences were detected in the allopregnanolone sensitivity of GnRH neurons recorded from juvenile and adult GnRH neurons. These results provide the first evidence for a direct action of the neurosteroid allopregnanolone on postnatal GnRH neurons and suggest a new mechanism through which fluctuating progesterone levels may influence the secretory activity of these important neurons in the female mouse.

Daily Activity and Body Temperature Rhythms Do Not Change Simultaneously With Age in Laboratory Mice

Daily rhythms of locomotor activity (AR) and body temperature (TR) were investigated in juvenile, adult, and senile female laboratory mice (5, 16, or 65 weeks old). All daily patterns were bimodal, with a main maximum in the dark and a secondary one immediately following lights on. The juvenile mice showed the highest magnitude of oscillation of the AR but the lowest magnitude of the TR; the magnitudes of the TR of adult and senile animals were not different, whereas those of AR in senile mice approached zero. For the AR, but not the TR, a phase advance with age was observed. The effect of locomotor activity on the body temperature was higher during the light time (minimum of motor activity) than during the dark time (maximum activity), and was least in juvenile mice. The calculated daily temperatures corresponding to zero activity gave rhythms that showed no age-dependent differences in daily mean or magnitude. This implies that the age-dependent changes of the TR were due mainly to masking effects.

MK-801 and male odours induce c-fos expression in the AOB of juvenile female mice.

The odours of adult males, which accelerate the timing of puberty of female mice, activate c-fos in the accessory olfactory bulb (AOB). To test the hypothesis that NMDA receptors are involved in the male odour-induced increase in c-fos expression, we studied the effects of the non-competitive NMDA receptor agonist MK-801 on male odour-induced c-fos expression in the AOB of juvenile female mice. Surprisingly, MK-801 increased FOS-like immunoreactivity (FLI) within the AOB in the absence of male odour and had no effect on male odour-induced c-fos expression. We suggest that MK-801 increases AOB mitral cell activity by disinhibiting GABAergic granule cells, resulting in increased c-fos expression throughout the AOB.

Effect of chronic cocaine on reproduction in female house mice

The effect of chronic cocaine exposure on the reproductive success of juvenile female house mice was studied. We followed two generations of female mice to examine the consequence of cocaine treatment on developmental and reproductive parameters such as weight gain, first estrus, impregnation, fertility, and maternal success. Twenty-two-day-old female mice were given cocaine at a daily total of 40 mg/kg body weight, delivered by two SC injections of 20 mg/kg each, until they were mated and inseminated by experienced males. The treatment attenuated weight gain and delayed puberty in the females but had no discernible effect on their pups. Administration of cocaine to lactating mothers decreased the weaning weight of their pups. Juvenile females previously nursed by mothers receiving cocaine and receiving 40 mg/kg cocaine daily themselves were impregnated at older ages than controls. Nevertheless, once these juveniles reached puberty, they mated succesfully and their reproductive parameters did not differ from those of control mice. Thus, chronic cocaine treatment of juvenile female mice slows body growth and development but has little effect of the offspring produced later when they reached adulthood.

Inhibition of sexual maturation in juvenile female and male mice by a chemosignal of female origin

Maturation of juvenile house mice ( Mus domesticus) exposed to synthetic 2,5-dimethylpyrazine was compared to the maturation of juvenile male and female mice exposed to urine from adult males and grouped females. Exposure of juvenile male mice to the synthetic compound significantly inhibited the growth of their testes and sex-accessory glands in a fashion similar to the urine of adult males and grouped females. The uterine weight and the presence of ova in the oviducts in females was strongly affected by synthetic stimuli. The majority of females (76–84%) exposed either to grouped females' urine or to the synthetic compound did not exhibit significant uterine weight increase and did not achieve pubertal ovulation before the age of 30 days as it has been reported for control mice. It is suggested that 2,5-dimethylpyrazine delays puberty of juvenile conspecifics in a population and may function whenever the living conditions of growing animals are below the level required for successful reproduction.

Resynchronization of the circadian corticosterone rhythm after a light/dark shift in juvenile and adult mice.

Most of the extensive literature concerning the resynchronization of circadian rhythms after a Zeitgeber shift is devoted to the dependence of resynchronization on the mode of the shift and the strength of the Zeitgeber, as well as on the circadian function investigated. Ontogenetic influences have rarely been investigated. Therefore, we studied the resynchronization of several circadian rhythms in juvenile and adult female laboratory mice. We present here the results concerning the corticosterone rhythm. The daily rhythms were determined as transverse profiles (2-h intervals) before as well as 3, 7, and 14 days after an 8-h phase delay of the light/dark cycle produced by a single prolongation of dark time. The corticosterone concentration in serum was determined radioimmunologically. In the control animals the daily patterns were bimodal, with main maxima at the end of the light time and secondary ones just after lights on. Ontogenetic differences were small. In adult mice the amplitude was slightly increased due to an increase in the maximum values, and the time of highest hormone concentrations was slightly phase advanced. In juvenile mice, a distinct daily pattern with a phase position in relation to the light/dark cycle corresponding to that of control animals was present on the 3rd day after the Zeitgeber shift. The daily mean as well as the minimum and maximum values increased initially and reached the values of control animals during the second week. In adult animals, a pronounced daily rhythm with the normal phase position was present only at the 7th postshift day. The amplitude, daily mean, and maximum values were decreased, and the minimum values were increased. The initial values were not reached even after 2 weeks. The results show that resynchronization was faster in juvenile mice compared with adult mice. As a possible cause for the observed age-related differences, a not yet stabilized phase-coupling between various circadian rhythms is supposed.

Effect of cocaine on the production of puberty-accelerating pheromone by male mice

This study examined whether chronic cocaine exposure could reduce reproductive fitness of adult male mice by interfering with their production of the puberty-accelerating pheromone, an androgen-dependent urinary pheromone that accelerates puberty in juvenile female mice. Administered at a high dose of 60 mg/kg body weight/day, cocaine caused mortality, body weight loss, and suppression of circulating testosterone during the first week of treatment. However, at 40 mg/kg/day, it resulted in little adverse effect of these parameters. Animals showed habituation to repeated cocaine exposure by regaining part of the lost weight and reelevating suppressed testosterone level at later stages of treatment. Urine samples collected from animals receiving 60 mg/kg cocaine daily for 2 weeks lost the puberty-accelerating effect. However, neither a 3-day treatment of the same dose nor a lower dose of 40 mg/kg reduced the effectiveness. The diminished effect of cocaine-treated male mouse urine might reflect lowered testosterone levels with a lag of 10 to 15 days, similar to that of castrated male mouse urine . These results indicate that cocaine has no direct effect on the production of priming pheromone, and its metabolites in the urine did not affect the response of juvenile females to the pheromone.

Odor-induced sexual maturation and expression of c- fos in the olfactory system of juvenile female mice

Exposure to the urine or soiled bedding odors of novel adult males is known to accelerate puberty in juvenile female mice. To determine what part of the olfactory system is activated by these odors, the expression of c- fos in the main olfactory bulb (MOB) and the accessory olfactory bulb (AOB) of juvenile female mice was examined after their exposure to male-soiled bedding, peppermint odor or their own bedding. Fos-like immunoreactivity was found throughout the AOB of the juvenile female mice exposed to the bedding odors of adult males for 3 h. In contrast, dense staining was found in the granular cell layer of the MOB of mice exposed to peppermint odors for 3 h, whereas mice exposed to their own bedding failed to show immunostaining in the AOB and only slight or no staining in the MOB. These results indicate that social odors stimulate the expression of c- fos in the AOB while non-social odors activate the MOB. This method allows the identification of individual cells activated by the different odors and will be useful in locating other areas of the brain involved in the neuroendocrine changes underlying odor-induced precocious puberty.

Sex-related differences in meprin-A, a membrane-bound mouse kidney proteinase

To investigate the expression of meprin-A, a brush-border metalloproteinase in mouse tissues, immunohistochemical studies were conducted using a monoclonal antibody prepared against a purified form of kidney meprin-A form male mice. Kidney slices from female mice displayed markedly less immunoreactivity compared with similar preparations from male mice using this antibody. However, the specific activities of meprin-A in kidney homogenates and purified preparations of meprin-A from male and female mice were not significantly different. Western blots of kidney membrane proteins from several mouse strains indicated that the female form of meprin-A had a decreased mobility relative to the male form when subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis; this difference could be eliminated by treatment of preparations with endoglycosidase F, which removes some asparagine-linked oligosaccharides. These data and lectin blots of membrane proteins indicate that there are differences in the glycosylation (specifically in the complex type oligosaccharides) of meprin-A in adult (8 wk old) male and female mice. Juvenile (3 wk old) male and female mice displayed similar amounts of immunohistochemical staining in kidney slices, as well as similar meprin-A electrophoretic mobilities and lectin affinities. Administration of 17 beta-estradiol to gonadectomized adult mice decreased the immunoreactivity of meprin-A in kidney slices and the electrophoretic mobility of meprin-A. These studies indicate that estrogens affect posttranslational modifications of meprin-A.

Cancer promotion in a mouse‐skin model by a 60‐Hz magnetic field: II. Tumor development and immune response

This paper describes preliminary findings on the influence of 60-Hz (2-mT) magnetic fields on tumor promotion and co-promotion in the skins of mice. The effect of magnetic fields on natural killer (NK) cell activity in spleen and blood was also examined. Groups of 32 juvenile female mice were exposed to the magnetic field as described in part I. The dorsal skin of all animals was treated with a subthreshold dose of the carcinogen 7,12-dimethyl-benz(a)anthracene (DMBA). One week after the treatment, two groups were sham exposed (group A) or field exposed at 2 mT (group B) 6 h/day for 21 weeks, to test whether the field would act as a tumor promoter. No tumors developed in these two groups of mice. To test whether the magnetic field would modify tumor development by directly affecting tumor growth or by suppressing immune surveillance, two additional groups of mice were treated weekly with the tumor promoter 12-0-tetradecanoylphorbol-13-acetate (TPA) and then either sham exposed (group C) or field exposed (group D). The time to appearance of tumors was shorter (but not statistically so) in the group exposed to magnetic fields and TPA. Some differences in NK cell activity and spleen size were observed between the sham- and field-exposed groups.

Sex and age mortality responses in zinc acetate-treated mice.

In regard to trace metal treatment or exposure, a number of variables are known to affect the expression of toxicity concerning its time course and degree. For example, known variables are route of administration, anionic component of the test substance, and sex and age of the recipient animal. Concerning the latter, little, if any, data have been reported dealing with sex- and age-related responses to excess zinc in mammalian systems. The primary purpose of the short communication presented here focuses on the determination of median lethal dose in sexually immature, i.e., juvenile, and adult female and male mice following a single zinc acetate insult. In addition, variation of lethality responses was examined with the age and sex groups to a divided treatment of a lethal dosage of zinc acetate, the injections of which were separated by various intervals.

Induction of a Puberty-Regulating Chemosignal in Wild Mouse Populations

The density of females in wild house mouse populations confined to highway cloverleafs was experimentally altered by adding foreign females. Urine collected from resident females before and after the additions was tested for its ability to delay puberty in juvenile female mice. Only urine collected after density was increased caused a significant delay of puberty. These results suggest that a urinary chemosignal produced in response to increased density may reduce population growth rate by increasing generation time. In a separate study, the fate of female mice introduced to a highway cloverleaf population was examined. Intensive mark-recapture trapping during 3 weeks following introduction of foreign females revealed high mortality and/or emigration rates for this group. However, the interlopers remained on the cloverleaf long enough to transiently increase the female interaction rate, which presumably mediates production of the puberty-delay pheromone.

Nickel acetate-induced mortality in mice of different ages.

Nickel has been shown to be related to a wide variety of pathophysiological conditions spanning a broad spectrum of events from gamete formation to the attainment of sexual maturity. There is, however, little, if any data available in regard to nickel toxicity in animals of different ages and sex. The purpose of this study was to determine the time course and extent of nickel-induced lethality in juvenile male and female mice and to compare juvenile responses to those in adult mice of both sexes.

Kinship affects puberty acceleration in mice (Mus musculus)

Juvenile female mice (Mus musculus) were exposed to the soiled bedding of unfamiliar males of different degrees of genetic relatedness. Females exposed to the soiled bedding of first cousins and unrelated males show an acceleration of first oestrus relative to controls. In contrast, females exposed to the soiled bedding of fathers or uncles show no such acceleration.

Puberty delay by a urinary cue from female house mice in feral populations.

Urine produced by wild female house mice, living in high- and low-density populations and confined to areas within a highway cloverleaf, was tested for its ability to delay puberty in juvenile female mice. Only urine collected from females in the dense population at its maximum density delayed puberty in test females. Urine collected when the population was less dense, or from a population that remained sparse, failed to delay puberty. These results suggest that a urinary factor present at high densities may delay puberty and thus help to slow further population growth.

Seasonal variation in litter size, bodyweight and sexual maturation in juvenile female house mice (Mus musculus).

Over a 4-year period a higher proportion of mated females bore litters during spring and summer than in late autumn and winter. Litter sizes were larger and young female mice weighed more at 21 days of age during spring and summer than at other times. However, young females attained sexual maturity, as indicated by vaginal smears, earlier during the winter months. This contrasts with data indicating that pubertal female mice have lower uterine weights in winter, A multiple regression analysis revealed that mouse bodyweights at 35 days of age and at 1st oestrus were important variables for predicting the age of puberty. Possible factors influencing reproductive seasonality in female house mice maintained under laboratory conditions are discussed.