In vitro exposure of male and female mice gametes to cadmium chloride during the fertilization process, and its effects on pregnancy outcome

In the liver, energy homeostasis is mainly regulated by mechanistic target of rapamycin (mTOR) signalling, which influences relevant metabolic pathways, including lipid metabolism. However, the Hedgehog (Hh) pathway is one of the newly identified drivers of hepatic lipid metabolism. Although the link between mTOR and Hh signalling was previously demonstrated in cancer development and progression, knowledge of their molecular crosstalk in healthy liver is lacking. To close this information gap, we used a transgenic mouse model, which allows hepatocyte-specific deletion of the Hh pathway, and in vitro studies to reveal interactions between Hh and mTOR signalling. The study was conducted in male and female mice to investigate sexual differences in the crosstalk of these signalling pathways. Our results reveal that the conditional Hh knockout reduces mitochondrial adenosine triphosphate (ATP) production in primary hepatocytes from female mice and inhibits autophagy in hepatocytes from both sexes. Furthermore, in vitro studies show a synergistic effect of cyclopamine and rapamycin on the inhibition of mTor signalling and oxidative respiration in primary hepatocytes from male and female C57BL/6N mice. Overall, our results demonstrate that the impairment of Hh signalling influences mTOR signalling and therefore represses oxidative phosphorylation and autophagy.

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Abstract 153: Inhibition of the 5-a-reductase Reduces Cardiac Hypertrophy and Improves Cardiac Function

Circulation Research ◽

10.1161/res.113.suppl_1.a153 ◽

2013 ◽

Vol 113 (suppl_1) ◽

Author(s):

Carolin Zwadlo ◽

Natali Froese ◽

Johann Bauersachs ◽

Joerg Heineke

Keyword(s):

Cardiac Hypertrophy ◽

Weight Ratio ◽

Capillary Density ◽

Left Ventricular ◽

Heart Weight ◽

Rat Cardiomyocytes ◽

Male And Female ◽

Female Mice

Objectives: Left ventricular hypertrophy (LVH) is an independent risk factor for increased cardiovascular mortality and a precursor of heart failure. Gender-specific differences point to a pivotal role of androgens in the development of pathological LVH. Dihydrotestosterone (DHT) is metabolized from testosterone via the enzyme 5-α-reductase. The 5-α-reductase is upregulated in the hypertrophied myocardium, leading to our assumption that DHT rather than testosterone is the crucial component in the development of LVH and might therefore constitute a potential therapeutic target. Methods: One week after transverse aortic constriction (TAC) or sham surgery male wild-type mice were treated for 2 weeks via an oralgastric tube with the 5-α-reductase inhibitor finasteride (daily dose 25mg/kg BW) or were left untreated (controls). Male and female transgenic Gαq (TG, a model of dilative cardiomyopathy) or non-transgenic mice were treated with finasteride for 6 weeks. Results: Cardiac hypertrophy after TAC was dramatically reduced by finasteride in male mice (heart weight/ body weight ratio, HW/BW in mg/g: control 6.65±0.35 versus finasteride treated 5.23±0.3; p<0.01). The reduced hypertrophy in these mice was accompanied by a reduction in cardiomyocyte diameter, ANP expression and fibrosis, but increased capillary density and Serca2a expression. Accordingly, finasteride also markedly reduced hypertrophy in isolated primary rat cardiomyocytes in vitro . Amelioration of hypertrophy by finasteride was associated with blunted activation of the prohypertrophic kinase mTOR in vitro and in vivo . Left ventricular dilation in male Gαq TG mice was markedly reduced by treatment with finasteride, which also led to an improvement in left ventricular function (determined as fractional area change in % by echocardiography: finasteride 44.72±1.71 vs. control 32.8±3.84, p<0.05) and a similar trend was observed in female mice. Interestingly, finasteride reduced pulmonary congestion in male and female mice alike. Conclusion: Finasteride treatment reduces hypertrophy and eccentric cardiac remodelling in mice, indicating a possible involvement of DHT in these processes as well as a potential benefit of 5-α-reductase inhibition in cardiac disease.

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ULTRASTRUCTURAL STUDY ON THE TEGUMENTAL ALTERATIONS OF MALE AND FEMALE SHISTOSOMA MANSONI Following IN VITRO EXPOSURE TO CURCUMIN

THE EGYPTIAN JOURNAL OF EXPERIMENTAL BIOLOGY (Zoology) ◽

10.5455/egysebz.20170826125825 ◽

2017 ◽

Vol 13 (2) ◽

pp. 1

Author(s):

Nabila Mira

Keyword(s):

Ultrastructural Study ◽

Male And Female ◽

In Vitro Exposure

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Estrogen responsiveness of bone formation in vitro and altered bone phenotype in aged estrogen receptor-α-deficient male and female mice

Acta Endocrinologica ◽

10.1530/eje.1.01832 ◽

2005 ◽

Vol 152 (2) ◽

pp. 301-314 ◽

Cited By ~ 38

Author(s):

Vilhelmiina Parikka ◽

ZhiQi Peng ◽

Teuvo Hentunen ◽

Juha Risteli ◽

Teresa Elo ◽

...

Keyword(s):

Bone Marrow ◽

Bone Formation ◽

Bone Marrow Cells ◽

Type I ◽

Wild Type ◽

Male And Female ◽

Female Mice ◽

Bone Phenotype ◽

Marrow Cells

Objective: Although the beneficial effects of estrogen on bone are well known, the roles of estrogen receptors (ERs) in mediating these effects are not fully understood. Methods: To study the effects of long-term ERα deficiency, bone phenotype was studied in aged ERα knockout (ERKO) mice. In addition, ERKO osteoclasts and osteoblasts were cultured in vitro. Design and results: Histomorphometric analysis showed that the trabecular bone volume and thickness were significantly increased and the rate of bone formation enhanced in both male and female ERKO mice in comparison to the wild-type animals. In ERKO males, however, the bones were thinner and their maximal bending strengths decreased. Consistent with previous reports, the bones of knockout mice, especially of female mice, were shorter than those of wild-type mice. In addition, the growth plates were totally absent in the tibiae of aged ERKO females, whereas the growth plate cartilages were detectable in wild-type females as well as in all the males. Analysis of cultured bone marrow cells from 10- to 12-week-old mice demonstrated that 17β-estradiol could stimulate osteoblastic differentiation of bone marrow cells derived from ERKO mice relatively to the same extent as those derived from wild-type mice. This was demonstrated by increases in synthesis of type I collagen, activity of alkaline phosphatase and accumulation of calcium in cultures. Total protein content was, however, reduced in ERKO osteoblast cultures. Conclusions: These results show altered bone phenotype in ERKO mice and demonstrate the stimulatory effect of estrogen on osteoblasts even in the absence of full-length ERα.

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Loss of CREBRF Reduces Anxiety-like Behaviors and Circulating Glucocorticoids in Male and Female Mice

Endocrinology ◽

10.1210/endocr/bqaa163 ◽

2020 ◽

Vol 161 (11) ◽

Author(s):

Krystle A Frahm ◽

Akeem A Williams ◽

Ashlee N Wood ◽

Michael C Ewing ◽

Polly E Mattila ◽

...

Keyword(s):

Stress Responses ◽

Acute Stress ◽

Plasma Corticosterone ◽

Affective States ◽

Male And Female ◽

Female Mice ◽

Glucocorticoid Signaling ◽

Plus Maze ◽

The Impact

Abstract Glucocorticoid signaling controls many key biological functions ranging from stress responses to affective states. The putative transcriptional coregulator CREB3 regulatory factor (CREBRF) reduces glucocorticoid receptor levels in vitro, suggesting that CREBRF may impact behavioral and physiological outputs. In the present study, we examined adult male and female mice with global loss of CREBRF (CrebrfKO) for anxiety-like behaviors and circulating glucocorticoids in response to various acute stress conditions. Results demonstrate that both male and female CrebrfKO mice have preserved locomotor activity but reduced anxiety-like behaviors during the light–dark box and elevated plus maze. These behavioral phenotypes were associated with lower plasma corticosterone after restraint stress. Further studies using unhandled female mice also demonstrated a loss of the diurnal circulating corticosterone rhythm in CrebrfKO mice. These results suggest that CREBRF impacts anxiety-like behavior and circulating glucocorticoids in response to acute stressors and serves as a basis for future mechanistic studies to define the impact of CREBRF in glucocorticoid-associated behavioral and physiological responses.

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Augmenting Renal Lymphatic Density Prevents Angiotensin II-Induced Hypertension in Male and Female Mice

American Journal of Hypertension ◽

10.1093/ajh/hpz139 ◽

2019 ◽

Vol 33 (1) ◽

pp. 61-69 ◽

Cited By ~ 4

Author(s):

Dakshnapriya Balasubbramanian ◽

Catalina A Lopez Gelston ◽

Alexandra H Lopez ◽

Geina Iskander ◽

Winter Tate ◽

...

Keyword(s):

Angiotensin Ii ◽

Lymphatic Vessel ◽

Immune Cell ◽

Peritoneal Macrophages ◽

Lymphatic Endothelial Cells ◽

Male And Female ◽

Female Mice ◽

Induced Hypertension ◽

Lymphatic Density

Abstract BACKGROUND Renal inflammation and immune cell infiltration are characteristic of several forms of hypertension. Our laboratory has previously demonstrated that renal-inflammation-associated lymphangiogenesis occurs in salt-sensitive and nitric-oxide-inhibition-induced hypertension. Moreover, enhancing renal lymphatic density prevented the development of these two forms of hypertension. Here, we investigated the effects of angiotensin II-induced hypertension on renal lymphatic vessel density in male and female mice. METHODS Wild-type and genetically engineered male and female mice were infused with angiotensin II for 2 or 3 weeks. Isolated splenocytes and peritoneal macrophages from mice, and commercially available mouse lymphatic endothelial cells were used for in vitro studies. RESULTS Compared to vehicle controls, angiotensin II-infused male and female mice had significantly increased renal lymphatic vessel density in association with pro-inflammatory immune cells in the kidneys of these mice. Direct treatment of lymphatic endothelial cells with angiotensin II had no effect as they lack angiotensin II receptors; however, angiotensin II treatment of splenocytes and peritoneal macrophages induced secretion of the lymphangiogenic growth factor VEGF-C in vitro. Utilizing our genetic mouse model of inducible renal lymphangiogenesis, we demonstrated that greatly augmenting renal lymphatic density prior to angiotensin II infusion prevented the development of hypertension in male and female mice and this was associated with a reduction in renal CD11c+F4/80- monocytes. CONCLUSION Renal lymphatics play a significant role in renal immune cell trafficking and blood pressure regulation, and represent a novel avenue of therapy for hypertension.

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Studies on the dominant-lethal and fertility effects of the heavy metal compounds methylmercuric hydroxide, mercuric chloride, and cadmium chloride in male and female mice

Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis ◽

10.1016/0027-5107(75)90007-x ◽

1975 ◽

Vol 30 (3) ◽

pp. 365-374 ◽

Cited By ~ 37

Author(s):

Kurt E. Sutler

Keyword(s):

Heavy Metal ◽

Mercuric Chloride ◽

Cadmium Chloride ◽

Metal Compounds ◽

Male And Female ◽

Female Mice ◽

Dominant Lethal

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Functional impact of diaphragm muscle sarcopenia in both male and female mice

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00064.2015 ◽

2015 ◽

Vol 309 (1) ◽

pp. L46-L52 ◽

Cited By ~ 35

Author(s):

Sarah M. Greising ◽

Carlos B. Mantilla ◽

Juan S. Medina-Martínez ◽

Jessica M. Stowe ◽

Gary C. Sieck

Keyword(s):

Functional Limitations ◽

Diaphragm Muscle ◽

Specific Force ◽

Transdiaphragmatic Pressure ◽

Male And Female ◽

Female Mice ◽

Motor Behaviors ◽

Age Related

To perform a range of ventilatory and nonventilatory behaviors, the diaphragm muscle (DIAm) must be able to generate sufficient forces throughout the lifespan. We hypothesized that sarcopenia impacts DIAm force generation and thus limits performance of expulsive, higher force, nonventilatory behaviors. Male and female mice ( n = 79) at 6 and 24 mo of age (100 vs. 70–75% survival, respectively) were used to examine transdiaphragmatic pressure (Pdi) generation across motor behaviors in vivo and in vitro DIAm specific force. We found a significant effect of age on maximum Pdi (20–41% decline during tracheal occlusion and bilateral phrenic nerve stimulation), maximum DIAm specific force (30% decline), and DIAm fatigue resistance (15% increase). There were no differences between sexes in these age effects on DIAm performance. These results support our hypothesis that sarcopenia primarily impacts higher force, nonventilatory motor behaviors of the DIAm. Such functional limitations may have negative implications in the ability of the DIAm to generate forces needed for airway clearance in old age and thereby contribute to age-related respiratory complications.

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