Prenatal exposure to an environmentally relevant phthalate mixture alters ovarian steroidogenesis and folliculogenesis in the F1 generation of adult female mice

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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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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