Induction of murine α-foetoprotein synthesis by oestradiol

Abstract. The synthesis of murine α-foetoprotein (m-AFP) was induced in 43 out of 47 adult mice of both sexes by sc administration of 100 μg oestradiol-17β every second day. The m-AFP serum levels of the oestrogen treated male and female mice were 7 and 17%, respectively, of the levels in mice during late pregnancy. Immunohistochemical examination of liver tissue revealed the intracellular presence of m-AFP in less than 0.5% of the hepatocytes scattered throughout the liver of the oestrogen treated mice.

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CTRP3 deficiency reduces liver size and alters IL-6 and TGFβ levels in obese mice

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00248.2015 ◽

2016 ◽

Vol 310 (5) ◽

pp. E332-E345 ◽

Cited By ~ 28

Author(s):

Risa M. Wolf ◽

Xia Lei ◽

Zhi-Chun Yang ◽

Maeva Nyandjo ◽

Stefanie Y. Tan ◽

...

Keyword(s):

Serum Levels ◽

Whole Body ◽

Activity Levels ◽

Loss Of Function ◽

Physiological Control ◽

Liver Size ◽

Male And Female ◽

Female Mice ◽

Obesity And Diabetes ◽

Similar Weight

C1q/TNF-related protein 3 (CTRP3) is a secreted metabolic regulator whose circulating levels are reduced in human and rodent models of obesity and diabetes. Previously, we showed that CTRP3 infusion lowers blood glucose by suppressing gluconeogenesis and that transgenic overexpression of CTRP3 protects mice against diet-induced hepatic steatosis. Here, we used a genetic loss-of-function mouse model to further address whether CTRP3 is indeed required for metabolic homeostasis under normal and obese states. Both male and female mice lacking CTRP3 had similar weight gain when fed a control low-fat (LFD) or high-fat diet (HFD). Regardless of diet, no differences were observed in adiposity, food intake, metabolic rate, energy expenditure, or physical activity levels between wild-type (WT) and Ctrp3-knockout (KO) animals of either sex. Contrary to expectations, loss of CTRP3 in LFD- or HFD-fed male and female mice also had minimal or no impact on whole body glucose metabolism, insulin sensitivity, and fasting-induced hepatic gluconeogenesis. Unexpectedly, the liver sizes of HFD-fed Ctrp3-KO male mice were markedly reduced despite a modest increase in triglyceride content. Furthermore, liver expression of fat oxidation genes was upregulated in the Ctrp3-KO mice. Whereas the liver and adipose expression of profibrotic TGFβ1, as well as its serum levels, was suppressed in HFD-fed KO mice, circulating proinflammatory IL-6 levels were markedly increased; these changes, however, were insufficient to affect systemic metabolic outcome. We conclude that, although it is dispensable for physiological control of energy balance, CTRP3 plays a previously unsuspected role in modulating liver size and circulating cytokine levels in response to obesity.

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Lead in the Water Supply Alters Swimming-Maze Behavior in Adult Mice

Perceptual and Motor Skills ◽

10.2466/pms.1982.55.2.507 ◽

1982 ◽

Vol 55 (2) ◽

pp. 507-512 ◽

Cited By ~ 1

Author(s):

K. Mc Lean ◽

G. H. Parker ◽

M. A. Persinger

Keyword(s):

Drinking Water ◽

Water Supply ◽

Tap Water ◽

Test Block ◽

Food Regime ◽

Male And Female ◽

Female Mice ◽

Adult Mice ◽

Body Weights ◽

Ad Libitum

After about two weeks of exposure to either 20 ppm or approximately 2000 ppm of lead in the drinking water or tap water only and under an ad libitum or restricted food regime, albino male and female mice ( N = 48) were tested for three consecutive days (3 blocks of 3 trials per day) in a swimming maze. Body weights were not altered by lead treatments significantly. The mice treated with the lead displayed longer escape latencies and more errors than the controls on tap water. Statistically significant interactions of lead treatment by test day by test block were also apparent.

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Membrane progesterone receptor-β, but not -α, in dorsal brain stem establishes sex-specific chemoreflex responses and reduces apnea frequency in adult mice

Journal of Applied Physiology ◽

10.1152/japplphysiol.00397.2016 ◽

2016 ◽

Vol 121 (3) ◽

pp. 781-791 ◽

Cited By ~ 10

Author(s):

Ryma Boukari ◽

Orlane Rossignol ◽

Cécile Baldy ◽

François Marcouiller ◽

Aida Bairam ◽

...

Keyword(s):

Brain Stem ◽

Progesterone Receptors ◽

Respiratory Control ◽

Staining Intensity ◽

Whole Body ◽

Male And Female ◽

Female Mice ◽

Adult Mice ◽

Specific Effects ◽

Membrane Progesterone Receptor

We tested the hypothesis that membrane progesterone receptors (mPR) contribute to respiratory control in adult male and female mice. Mice were implanted with osmotic minipumps for continuous infusion of small interfering RNA (siRNA) directed against mPRα, mPRβ, or a control solution in the fourth ventricle (to target brain stem respiratory areas) for 14 days. We then performed respiratory and metabolic recordings by whole body plethysmography at rest and in response to hypoxia (12% O2) or hypercapnia (5% CO2, 5 min each). For each treatment, we have verified with immunohistochemistry that the staining intensity of mPRα or mPRβ in the brain stem is decreased. At rest, the siRNA against mPRα and mPRβ increased respiratory frequency in males only. The siRNA against mPRβ almost tripled the frequency of apneas in male and in female mice, while the siRNA against mPRα had no effect. Regarding respiratory chemoreflex, the siRNA against mPRβ suppressed the response to hypoxia in male and female mice and reduced by ∼50% the response to hypercapnia, while the siRNA against mPRα had more limited effects. Interestingly, control females had higher ventilatory response to hypoxia and hypercapnia than males, and these sex-specific effects were suppressed by the siRNA against mPRβ, whereas they were still present after treatment with the siRNA against mPRα. We conclude that mPRβ reduces apnea frequency in male and female mice and establishes sex-specific ventilatory chemoreflex.

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Suppression of expulsion ofAspiculuris tetrapterain hydrocortisone and methotrexate treated mice

Parasitology ◽

10.1017/s0031182000053191 ◽

1975 ◽

Vol 71 (1) ◽

pp. 109-116 ◽

Cited By ~ 7

Author(s):

Jerzy M. Behnke

Keyword(s):

Primary Infection ◽

Larval Growth ◽

Male And Female ◽

Treated Male ◽

Female Mice ◽

The Third ◽

Delayed Rejection ◽

Aspiculuris Tetraptera ◽

Anterior Migration

Hydrocortisone treated male and female mice, given a primary infection withAspiculuris tetraptera, did not reject the worms during the third week of infection. Mice given hydrocortisone during the first week of infection had elevated worm burdens on day 10, suggesting that some worm loss was encountered during the anterior migration in control mice. Furthermore, this temporary period of treatment was sufficient totally to suppress rejection and to allow the parasite to persist until day 28. Methotrexate also significantly delayed rejection, but larval growth was retarded in treated mice. These results, it is suggested, add strength to the hypothesis that the loss ofA. tetrapterain a primary infection in mice, is an immunological phenomenon.

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Effects of Neonatal Caffeine Administration on Vessel Reactivity in Adult Mice

American Journal of Perinatology ◽

10.1055/s-0040-1712953 ◽

2020 ◽

Author(s):

Ajay Pratap Singh ◽

Praveen Chandrasekharan ◽

Sylvia Gugino ◽

Sara Berkelhamer ◽

Huamei Wang ◽

...

Keyword(s):

Chronic Stress ◽

Systemic Blood Pressure ◽

Systemic Hypertension ◽

Male Mice ◽

Treated Male ◽

Female Mice ◽

Adult Mice ◽

Specific Effects ◽

Lower Body Weight ◽

The Impact

Abstract Objective The effects of neonatal caffeine therapy in adults born preterm are uncertain. We studied the impact of neonatal caffeine on systemic blood pressure, vessel reactivity, and response to stress in adult mice. Study Design Mice pups were randomized to caffeine (20 mg/kg/d) or saline by intraperitoneal injection for 10 days after birth. We performed tail-cuff BP (8/12 weeks), urinary 8-hydroxydeoxyguanosine and fecal corticosterone (14 weeks), and vessel reactivity in aortic rings (16 weeks) in adult mice. Results No differences were noted in systolic, diastolic, and mean blood pressures between the two groups at 8 and 12 weeks of age. However, norepinephrine-induced vasoconstriction was substantially higher in aortic rings in CAF-treated male mice. More significant vasodilator responses to nitric oxide donors in aortic rings in female mice may suggest gender-specific effects of caffeine. Female mice exposed to caffeine had significantly lower body weight over-time. Caffeine-treated male mice had substantially higher fecal corticosterone and urinary 8-hydroxydeoxyguanosine at 14 weeks, suggestive of chronic stress. Conclusion We conclude sex-specific vulnerability to the heightened vascular tone of the aorta in male mice following neonatal caffeine therapy. Altered vessel reactivity and chronic stress in the presence of other risk factors may predispose to the development of systemic hypertension in adults born preterm.

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Impact of sex, androgens, and prostate size on C57BL/6J mouse urinary physiology: functional assessment

AJP Renal Physiology ◽

10.1152/ajprenal.00270.2019 ◽

2019 ◽

Vol 317 (4) ◽

pp. F996-F1009 ◽

Cited By ~ 4

Author(s):

Hannah Ruetten ◽

Kyle A. Wegner ◽

Helen L. Zhang ◽

Peiqing Wang ◽

Jaskiran Sandhu ◽

...

Keyword(s):

Clear Understanding ◽

Male Mice ◽

Intact Male ◽

Voiding Function ◽

Castrate Male ◽

Male And Female ◽

Female Mice ◽

Adult Mice ◽

Old Adult ◽

Effective Use

Laboratory mice are used to identify causes of urinary dysfunction including prostate-related mechanisms of lower urinary tract symptoms. Effective use of mice for this purpose requires a clear understanding of molecular, cellular, anatomic, and endocrine contributions to voiding function. Whether the prostate influences baseline voiding function has not been specifically evaluated, in part because most methods that alter prostate mass also change circulating testosterone concentrations. We performed void spot assay and cystometry to establish a multiparameter “baseline” of voiding function in intact male and female 9-wk-old (adult) C57BL/6J mice. We then compared voiding function in intact male mice to that of castrated male mice, male (and female) mice treated with the steroid 5α-reductase inhibitor finasteride, or male mice harboring alleles ( Pbsn4cre/+; R26RDta/+) that significantly reduce prostate lobe mass by depleting prostatic luminal epithelial cells. We evaluated aging-related changes in male urinary voiding. We also treated intact male, castrate male, and female mice with exogenous testosterone to determine the influence of androgen on voiding function. The three methods used to reduce prostate mass (castration, finasteride, and Pbsn4cre/+; R26RDta/+) changed voiding function from baseline but in a nonuniform manner. Castration feminized some aspects of male urinary physiology (making them more like intact female mice) while exogenous testosterone masculinized some aspects of female urinary physiology (making them more like intact male mice). Our results provide evidence that circulating testosterone is responsible in part for baseline sex differences in C57BL/6J mouse voiding function while prostate lobe mass in young, healthy adult mice has a lesser influence.

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EFFECT OF PREPUBERTY CASTRATION ON SUBSEQUENT CANCER IMPLANTATION

Journal of Experimental Medicine ◽

10.1084/jem.42.2.155 ◽

1925 ◽

Vol 42 (2) ◽

pp. 155-161 ◽

Cited By ~ 18

Author(s):

James B. Murphy ◽

Ernest Sturm

Keyword(s):

Adult Life ◽

The Other ◽

Male And Female ◽

Female Mice ◽

Adult Mice ◽

Other Hand ◽

Refractory State ◽

Early Adult Life ◽

Subsequent Cancer

Male and female mice castrated during the first 7 weeks of life and implanted with cancer at later periods show a resistance definitely higher than do intact animals of the same age. This increased refractiveness is evident at 3 months after the operation but is more pronounced at 8 months to a year. Even castration in early adult life seems to increase the refractory state to later cancer inoculation. On the other hand, adult mice inoculated within a week after castration show slight if any evidence of increased resistance.

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3024 Osteocyte-derived CXCL12 is Essential for Load-Induced Bone Formation in Adult Mice

Journal of Clinical and Translational Science ◽

10.1017/cts.2019.254 ◽

2019 ◽

Vol 3 (s1) ◽

pp. 111-111 ◽

Cited By ~ 1

Author(s):

Pamela Cabahug Zuckerman ◽

Chao Liu ◽

Emily Fang ◽

Alesha B Castillo

Keyword(s):

New York ◽

Bone Formation ◽

Critical Role ◽

New York University ◽

Cxcl12 Expression ◽

Male And Female ◽

Female Mice ◽

Adult Mice ◽

Basal Bone ◽

Underlying Mechanisms

OBJECTIVES/SPECIFIC AIMS: Our aim is to test whether osteocyte-specific CXCL12 expression is critical to exercise-driven bone formation. METHODS/STUDY POPULATION: All procedures were approved by the NEW YORK UNIVERSITY Institutional Animal Care and Use Committee. We generated male and female mice in which CXCL12 was deleted from OCYs (CXCL12ΔOCY) by crossing CXCL12 floxed mice and 10kb DMP1-Cre transgenic mice (gifts from Drs. Geoffrey Gurtner and Lynda Bonewald, respectively). The 10kb DMP1-Cre has been shown to be robustly expressed in odontoblasts and OCYs, with little to no activity in cells from non-mineralized tissues (Lu+ J Dent Res 2007). Growing male and female mice (n=3-8/group) were given fluorochrome labels every two weeks between 4-16 weeks of age, to monitor the role of CXCL12 during development. A second group, of adult 16-week-old mice (n=5/group), were subjected to tibial axial cyclic loading (1200µɛ, 2Hz, 120cycles, 3days/wk for 2 wks) (Liu+ Bone 2018). Basal and load-induced periosteal (Ps) and endosteal (Es) mineralizing surface (MS/BS, %), mineral apposition (MAR, µm/day) and bone formation rates (BFR/BS, µm3/µm2/year) were calculated (Dempster+ JBMR.2013) at mid-length. RESULTS/ANTICIPATED RESULTS: No significant differences were detected in basal bone formation during development. However, relative load-induced Ps MAR (rMAR) was reduced by 50% in female (p=0.02) and 75% in male (p=0.002) CXCL12ΔOCY mice; and similarly, Ps rBFR/BS was reduced by 50% in female (p=0.01) and 70% in male (p=0.001) CXCL12ΔOCY mice (Figure 1). Es bone formation was not affected by CXCL12 deletion. DISCUSSION/SIGNIFICANCE OF IMPACT: In summary, osteocyte-specific CXCL12 expression plays a critical role in exercise-driven periosteal new bone formation, suggesting that CXCL12 signaling may positively regulate osteogenic differentiation and/or mature osteoblast function. Further underlying mechanisms are currently being explored. Thus, osteocyte-specific CXCL12 signaling may be a promising target to enhance load-induced bone formation in patients with compromised ability to form new bone.

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Viscoelastic Coagulation Monitor (VCMVet) Reference Intervals and Sex Differences in Mature Adult Mice

Acta Haematologica ◽

10.1159/000516587 ◽

2021 ◽

pp. 1-8

Author(s):

Robert R. Rigor ◽

Linda M. Schutzman ◽

Joseph M. Galante ◽

Ian E. Brown

Keyword(s):

Sex Differences ◽

Molecular Mechanisms ◽

Alpha Angle ◽

Reference Intervals ◽

Coagulation Test ◽

Mature Adult ◽

Male And Female ◽

Female Mice ◽

Adult Mice ◽

Coagulation Status

Introduction: Viscoelastic coagulation tests are useful to assess coagulation status in the clinical setting and to aid in understanding underlying pathophysiological mechanisms that affect coagulation status. Such tests also are useful for coagulation research. Because mouse models are widely used to study molecular mechanisms in fine detail, a simple viscoelastic coagulation test requiring small blood volumes would be convenient for such studies in mice. Methods: We tested viscoelastic coagulation properties of normal healthy adult mice using a novel veterinary clinical point-of-care device, Viscoelastic Coagulation Monitor (VCM Vet™; Entegrion Corp.). Fresh whole blood was collected from 63 healthy mature adult C57 black 6N mice, with ultimately 54 mice, equal numbers of male and females, used to determine reference intervals (RIs) for VCM test parameters. Results: RIs were determined for equal numbers of male and female mice: clot time: 43.0–353.0 s; clot formation time: 49.4–137.6 s; alpha angle: 54.4–62.2°; A10: 25.0–49.6 VCM units; A20: 31.0–56.5 VCM units; maximum clot firmness: 37.6–62.8 VCM units; Lysis Index 30 (Li30): 99.8–100.0%; and Li45: 99.7–100.0%. Significant differences were found between male and female subgroups, where females had higher mean A10 and A20 and median MCF values, indicating greater clot firmness in female versus male mice. Conclusion: VCM Vet is a feasible viscoelastic coagulation test device for studies with mature adult mice, including studying inherent sex differences in coagulation parameters. Inherent differences in coagulability of male and female mice warrant further investigation to determine if such differences underlie greater coagulopathic, hemorrhagic, or thromboembolic risk during trauma or other pathophysiologic conditions.

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