Accurate Control of 17β-Estradiol Long-Term Release Increases Reliability and Reproducibility of Preclinical Animal Studies

Gérard, Céline; Gallez, Anne; Dubois, Clémence; Drion, Pierre; Delahaut, Philippe; Quertemont, Étienne; Noël, Agnès; Péqueux, Christel

doi:10.1007/s10911-016-9368-1

Cited by 16 publications

(12 citation statements)

References 33 publications

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“…In the present study, total T levels were maintained at the physiological level of the intact middle-aged males, which represents a low physiological dose of T. In addition, the Cheng study used commercial dissolvable pellets (Innovative Research of America), whereas we used silastic capsules. Previous studies demonstrate significant kinetic and supraphysiological dose release from commercial pellets, albeit for estradiol, that could affect outcomes [66-68]. Importantly, in our study, intact, STTD + T, and LTTD + T all achieved similar circulating T, suggesting that the duration of deprivation rather than the dose of T contributed to the detrimental effects in LTTD + T rats.…”

Section: Discussionsupporting

confidence: 54%

Chronic Testosterone Deprivation Sensitizes the Middle-Aged Rat Brain to Damaging Effects of Testosterone Replacement

et al. 2019

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Introduction: An increasing number of middle-aged men are being screened for low testosterone levels and the number of prescriptions for various forms of testosterone replacement therapy (TRT) has increased dramatically over the last 10 years. However, the safety of TRT has come into question with some studies suggesting increased morbidity and mortality. Objective: Because the benefits of estrogen replacement in postmenopausal women and ovariectomized rodents are lost if there is an extended delay between estrogen loss and replacement, we hypothesized that TRT may also be sensitive to delayed replacement. Methods: We compared the effects of testosterone replacement after shortterm (2 weeks) and long-term testosterone deprivation (LTTD; 10 weeks) in middle-aged male rats on cerebral ischemia, oxidative stress, and cognitive function. We hypothesized that LTTD would increase oxidative stress levels and abrogate the beneficial effects of TRT. Results: Hypogonadism itself and TRT after short-term castration did not affect stroke outcome compared to intact rats. However, after long-term hypogonadism in middle-aged male Fischer 344 rats, TRT exacerbated the detrimental behavioral effects of experimental focal cerebral ischemia, whereas this detrimental effect was prevented by administration of the freeradical scavenger tempol, suggesting that TRT exacerbates oxidative stress. In contrast, TRT improved cognitive performance in non-stroked rats regardless of the length of hypogonadism. In the Morris water maze, peripheral oxidative stress was highly associated with decreased cognitive ability. Conclusions: Taken together, these data suggest that TRT after long-term hypogonadism can exacerbate functional recovery after focal cerebral ischemia, but in the absence of injury can enhance cognition. Both of these effects are modulated by oxidative stress levels.

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Section: Discussionsupporting

confidence: 54%

Chronic Testosterone Deprivation Sensitizes the Middle-Aged Rat Brain to Damaging Effects of Testosterone Replacement

et al. 2019

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“…Bodyweight of normal and treated animals was measured daily. At days 21 and 60, eight mice from each group were sacrificed by rapid decapitation (Gérard et al, 2017).…”

Section: Methodsmentioning

confidence: 99%

Protective effects of Avena sativa against oxidative stress‐induced kidney damage resulting from an estrogen deficiency in ovariectomized Swiss mice model

et al. 2020

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The aim of this study was to evaluate the antioxidant capacity of Avena sativa and to confirm its protective effects on estrogen deficiency in ovariectomized mice (OVX) model. Animals were treated during 21 and 60 days as follows: negative control, positive control treated with oat, ovariectomized, and ovariectomized receiving hormonal or oat treatments, respectively. 21 days post‐surgery, our results showed that ovariectomy increases weight gain and urea level in plasma. After 60 days of treatment, OVX showed a gain in weight, high increases in relative kidney weight, plasmatic creatinine, glutathione peroxidase (GPX) activity, and protein oxidation as shown by elevated protein carbonyl (PCO) and advanced oxidation protein products (AOPP) levels. On the other side, a decrease was detected in catalase activity. Meanwhile, no significant changes in urea level, lipid peroxidation, SOD and GSH activity were detected. Conversely, supplementation with oat reduced weight gain, as well as oxidative stress and oxidation protein in the kidney of OVX mice. Practical applications In our study, we removed the two ovaries of adult female mice in order to eliminate the essential source of steroid hormones. Deficiency in these sexual hormones, especially estrogen, leads to several physiological and morphological disturbances that are found in post‐menopausal women. The gain in weight and oxidative kidney damages were the main health problems detected in ovariectomized animals. This work explored for the first time the use of oat grains as a safe natural remedy to treat all previous health problems and to avoid carcinogenic effects of the menopausal hormone therapy. Owing to its health benefits, this cereal species has recently gained attention as an important source of antioxidants and fibers. Thanks to these two components, it can be able to restore all indicated disturbances. Therefore, this cereal can be very useful in the prevention of obesity and kidney oxidative damage occurring during menopause.

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“…We aimed to assess the influence of estrogen during the sleep cycle; therefore, a slowrelease formulation may avoid undesirable pulsatile concentrations of estrogen and daily animal manipulation. 17) Silastic capsule implantation was performed in all male and female SHRs in the same procedure as in the animal preparation. The silastic capsules were artificially made through a 30-mm-long laboratory tubing (inner/ outer diameter: 1.6/3.2 mm, Dow Corning, VWR International, Buffalo Grove, IL, USA) containing 60 μg of 17βestradiol benzoate in 60 μL sesame oil.…”

Section: Estrogen Silastic Capsule Production and Implantationmentioning

confidence: 99%

The Impact of Estrogen Supplementation to Autonomic and Sleep Modulations in Free-Moving Spontaneously Hypertensive Rats

Liu

Lai²,

Chen³

et al. 2020

Int. Heart J.

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Sleep and estrogen levels have an impact on neural regulation and are associated with cardiovascular (CV) events. We investigated the effects of estrogen on heart rate variability (HRV) and circadian cycle in spontaneously hypertensive rats (SHRs). Polysomnographic recording was performed in seven male and seven female SHRs during sleep. The electroencephalogram (EEG) and electromyogram (EMG) were evaluated to define active waking (AW), quiet sleep (QS), and paradoxical sleep (PS) stages. Cardiac activities were measured by RR interval of the electrocardiogram (ECG), mean arterial pressure (MAP), and power spectrum of HRV. In ECG, estrogen prolonged the RR interval in total sleep when compared with that at baseline in male SHRs (203.74 ± 6.61 versus 181.30 ± 8.06 ms, P < 0.001) and in female SHRs (169.21 ± 6.43 versus 160.76 ± 10.66 ms, P < 0.05). In HRV, the estrogen increased the high frequency (HF) in total sleep when compared with that at baseline in male SHRs (1.03 ± 0.28 versus 0.60 ± 0.43 ln (ms 2), P < 0.001) and in female SHRs (0.71 ± 0.26 versus 0.42 ± 0.19 ln (ms 2), P < 0.05). In male SHRs, estrogen increased the frequency of QS (26.50 ± 4.85 versus 20.79 ± 5.07, P < 0.01) and PS (25.64 ± 5.18 versus 20.14 ± 4.75, P < 0.05) stages when compared with baseline. In female SHRs, estrogen increased the percentage of delta waves in total sleep (79.87% ± 3.10% versus 76.71% ± 2.74%, P < 0.05) when compared with that at baseline. In HRV, estrogen leads to neuromodulation by increased parasympathetic tone in all SHRs, suggesting a lower risk to CV events. In sleep analyses, estrogen in male SHRs caused poor sleep quality. In contrast, estrogen in female SHRs demonstrated improved quality of sleep and decreased risk of hypertension.

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Accurate Control of 17β-Estradiol Long-Term Release Increases Reliability and Reproducibility of Preclinical Animal Studies

Cited by 16 publications

References 33 publications

Chronic Testosterone Deprivation Sensitizes the Middle-Aged Rat Brain to Damaging Effects of Testosterone Replacement

Chronic Testosterone Deprivation Sensitizes the Middle-Aged Rat Brain to Damaging Effects of Testosterone Replacement

Protective effects of Avena sativa against oxidative stress‐induced kidney damage resulting from an estrogen deficiency in ovariectomized Swiss mice model

The Impact of Estrogen Supplementation to Autonomic and Sleep Modulations in Free-Moving Spontaneously Hypertensive Rats

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