Anxiety in adult female mice following perinatal exposure to chlorpyrifos

Abstract Background Exposure to the bioaccumulative pesticide dichlorodiphenyltrichloroethane (DDT) and its metabolite dichlorodiphenyldichloroethylene (DDE) has been associated with increased risk of insulin resistance and obesity in humans and experimental animals. These effects appear to be mediated by reduced brown adipose tissue (BAT) thermogenesis, which is regulated by the sympathetic nervous system. Although the neurotoxicity of DDT is well-established, whether DDT alters sympathetic innervation of BAT is unknown. We hypothesized that perinatal exposure to DDT or DDE promotes thermogenic dysfunction by interfering with sympathetic regulation of BAT thermogenesis. Methods Pregnant C57BL/6 J mice were administered environmentally relevant concentrations of DDTs (p,p’-DDT and o,p’-DDT) or DDE (p,p’-DDE), 1.7 mg/kg and 1.31 mg/kg, respectively, from gestational day 11.5 to postnatal day 5 by oral gavage, and longitudinal body temperature was recorded in male and female offspring. At 4 months of age, metabolic parameters were measured in female offspring via indirect calorimetry with or without the β3 adrenergic receptor agonist, CL 316,243. Immunohistochemical and neurochemical analyses of sympathetic neurons innervating BAT were evaluated. Results We observed persistent thermogenic impairment in adult female, but not male, mice perinatally exposed to DDTs or p,p’-DDE. Perinatal DDTs exposure significantly impaired metabolism in adult female mice, an effect rescued by treatment with CL 316,243 immediately prior to calorimetry experiments. Neither DDTs nor p,p’-DDE significantly altered BAT morphology or the concentrations of norepinephrine and its metabolite DHPG in the BAT of DDTs-exposed mice. However, quantitative immunohistochemistry revealed a 20% decrease in sympathetic axons innervating BAT in adult female mice perinatally exposed to DDTs, but not p,p’-DDE, and 48 and 43% fewer synapses in stellate ganglia of mice exposed to either DDTs or p,p’-DDE, respectively, compared to control. Conclusions These data demonstrate that perinatal exposure to DDTs or p,p’-DDE impairs thermogenesis by interfering with patterns of connectivity in sympathetic circuits that regulate BAT. Graphical abstract

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Diet-induced obesity resistance of adult female mice selectively bred for increased wheel-running behavior is reversed by single perinatal exposure to a high-energy diet

Physiology & Behavior ◽

10.1016/j.physbeh.2016.02.003 ◽

2016 ◽

Vol 157 ◽

pp. 246-257 ◽

Cited By ~ 4

Author(s):

Stefano Guidotti ◽

Neele Meyer ◽

Ewa Przybyt ◽

Anton J.W. Scheurink ◽

Martin C. Harmsen ◽

...

Keyword(s):

Adult Female ◽

Wheel Running ◽

High Energy ◽

Perinatal Exposure ◽

Female Mice ◽

Diet Induced Obesity ◽

Obesity Resistance

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Review for "Brain-derived acetylcholine maintains peak bone mass in adult female mice"

10.1002/jbmr.4024/v2/review2 ◽

2020 ◽

Keyword(s):

Bone Mass ◽

Adult Female ◽

Peak Bone Mass ◽

Female Mice

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Decision letter for "Brain-derived acetylcholine maintains peak bone mass in adult female mice"

10.1002/jbmr.4024/v2/decision1 ◽

2020 ◽

Keyword(s):

Bone Mass ◽

Adult Female ◽

Peak Bone Mass ◽

Female Mice

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Developmental androgen excess programs sympathetic tone and adipose tissue dysfunction and predisposes to a cardiometabolic syndrome in female mice

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00620.2012 ◽

2013 ◽

Vol 304 (12) ◽

pp. E1321-E1330 ◽

Cited By ~ 38

Author(s):

Kazunari Nohara ◽

Rizwana S. Waraich ◽

Suhuan Liu ◽

Mathieu Ferron ◽

Aurélie Waget ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Glucose Intolerance ◽

Adult Female ◽

Sympathetic Tone ◽

Visceral Adiposity ◽

Androgen Excess ◽

Altered Expression ◽

Female Mice ◽

The Impact

Among women, the polycystic ovarian syndrome (PCOS) is considered a form of metabolic syndrome with reproductive abnormalities. Women with PCOS show increased sympathetic tone, visceral adiposity with enlarged adipocytes, hypoadiponectinemia, insulin resistance, glucose intolerance, increased inactive osteocalcin, and hypertension. Excess fetal exposure to androgens has been hypothesized to play a role in the pathogenesis of PCOS. Previously, we showed that neonatal exposure to the androgen testosterone (NT) programs leptin resistance in adult female mice. Here, we studied the impact of NT on lean and adipose tissues, sympathetic tone in cardiometabolic tissues, and the development of metabolic dysfunction in mice. Neonatally androgenized adult female mice (NTF) displayed masculinization of lean tissues with increased cardiac and skeletal muscle as well as kidney masses. NTF mice showed increased and dysfunctional white adipose tissue with increased sympathetic tone in both visceral and subcutaneous fat as well as increased number of enlarged and insulin-resistant adipocytes that displayed altered expression of developmental genes and hypoadiponectinemia. NTF exhibited dysfunctional brown adipose tissue with increased mass and decreased energy expenditure. They also displayed decreased undercarboxylated and active osteocalcin and were predisposed to obesity during chronic androgen excess. NTF showed increased renal sympathetic tone associated with increased blood pressure, and they developed glucose intolerance and insulin resistance. Thus, developmental exposure to testosterone in female mice programs features of cardiometabolic dysfunction, as can be observed in women with PCOS, including increased sympathetic tone, visceral adiposity, insulin resistance, prediabetes, and hypertension.

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Model of induction of thyroid dysfunctions in adult female mice

Arquivo Brasileiro de Medicina Veterinária e Zootecnia ◽

10.1590/s0102-09352007000500022 ◽

2007 ◽

Vol 59 (5) ◽

pp. 1245-1249 ◽

Cited By ~ 11

Author(s):

E. Ferreira ◽

A.E. Silva ◽

R. Serakides ◽

A.E.S. Gomes ◽

G.D. Cassali

Keyword(s):

Drinking Water ◽

Adult Female ◽

Thyroid Dysfunction ◽

The State ◽

Female Mice ◽

Thyroid Dysfunctions ◽

Swiss Strain

It is described the elaboration of a protocol to induce hyperthyroidism and hypothyroidism in mice by administrating thyroxin and propylthiouracil, respectively, in the drinking water. The drugs were administered to adult female mice of the Swiss strain for 30 days in order to obtain a systemic status of thyroid dysfunction. The induction of hyperthyroidism and hypothyroidism in the animals was confirmed by the histomorphological analysis of the thyroid in the end of the experiment, when the state of gland dysfunction in the animals submitted to the treatment was observed.

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Perinatal exposure to 19-Nor-17α-ethynyltestosterone (norethindrone) influences morphology and aggressive behavior of female mice

Hormones and Behavior ◽

10.1016/0018-506x(81)90005-2 ◽

1981 ◽

Vol 15 (4) ◽

pp. 404-415 ◽

Cited By ~ 4

Author(s):

Ronald Gandelman ◽

Steven M. Howard ◽

June Machover Reinisch

Keyword(s):

Aggressive Behavior ◽

Perinatal Exposure ◽

Female Mice

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Fluoxetine exposure in adolescent and adult female mice decreases cocaine and sucrose preference later in life

Journal of Psychopharmacology ◽

10.1177/0269881118805488 ◽

2018 ◽

Vol 33 (1) ◽

pp. 145-153 ◽

Cited By ~ 5

Author(s):

Francisco J Flores-Ramirez ◽

Israel Garcia-Carachure ◽

David O Sanchez ◽

Celene Gonzalez ◽

Samuel A Castillo ◽

...

Keyword(s):

Drinking Water ◽

Conditioned Place Preference ◽

Early Development ◽

Adult Female ◽

Model System ◽

Psychotropic Medications ◽

Sucrose Preference ◽

Female Mice ◽

Male Subjects ◽

Conditioned Place Preference Paradigm

Background: Preclinical evidence from male subjects indicates that exposure to psychotropic medications, during early development, results in long-lasting altered responses to reward-related stimuli. However, it is not known if exposure to the antidepressant fluoxetine, in female subjects specifically, changes sensitivity to natural and drug rewards, later in life. Aims: The aim of this work was to investigate if exposure to fluoxetine mediates enduring changes in sensitivity to the rewarding properties of cocaine and sucrose, using female mice as a model system. Methods: We exposed C57BL/6 female mice to fluoxetine (250 mg/L in their drinking water) for 15 consecutive days, either during adolescence (postnatal day 35–49) or adulthood (postnatal day 70–84). Twenty-one days later, mice were examined on their behavioral reactivity to cocaine (0, 2.5, 5, 7.5 mg/kg) using the conditioned place preference paradigm, or assessed on the two-bottle sucrose (1%) test. Results: We found that regardless of age of antidepressant exposure, female mice pre-exposed to fluoxetine displayed reliable conditioning to the cocaine-paired compartment. However, when compared to respective age-matched controls, antidepressant pre-exposure decreased the magnitude of conditioning at the 5 and 7.5 mg/kg cocaine doses. Furthermore, fluoxetine pre-exposure reduced sucrose preference without altering total liquid intake. Conclusions: The data suggest that pre-exposure to fluoxetine, during adolescence or adulthood, results in a prolonged decrease in sensitivity to the rewarding properties of both natural and drug rewards in female C57BL/6 mice.

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