Diet-Independent Remodeling of Cellular Membranes Precedes Seasonally Changing Body Temperature in a Hibernator

Polyunsaturated fatty acids (PUFA) have a multitude of health effects. Their incorporation into membrane phospholipids (PL) is generally believed to depend directly on dietary influx. PL influence transmembrane protein activity and thus can compensate temperature effects; e.g. PL n-6 PUFA are thought to stabilize heart function at low body temperature (Tb), whereas long chain (>C18) n-3 PUFA may boost oxidative capacity. We found substantial remodeling of membranes in free-living alpine marmots which was largely independent of direct dietary supply. Organ PL n-6 PUFA and n-6 to n-3 ratios were highest at onset and end of hibernation after rapid increases during a brief transitional period prior to hibernation. In contrast, longer chain PL n-3 PUFA content was low at end of summer but maximal at end of hibernation. After termination of hibernation in spring, these changes in PL composition were rapidly reversed. Our results demonstrate selective trafficking of PUFA within the body, probably governed by a circannual endogenous rhythm, as hibernating marmots were in winter burrows isolated for seven months from food and external cues signaling the approaching spring. High concentrations of PL n-6 PUFA throughout hibernation are in line with their hypothesized function of boosting SERCA 2a activity at low Tb. Furthermore, we found increasing rate of rewarming from torpor during winter indicating increasing oxidative capacity that could be explained by the accumulation of long-chain PL n-3 PUFA. It may serve to minimize the time necessary for rewarming despite the increasing temperature range to be covered, because rewarming is a period of highest metabolic rate and hence production of reactive oxygen species. Considering the importance of PUFA for health our results may have important biomedical implications, as seasonal changes of Tb and associated remodeling of membranes are not restricted to hibernators but presumably common among endothermic organisms

Vaginal Er:YAG laser application in the menopausal ewe model: a randomised estrogen and sham-controlled trial

Objective: To describe effects of non-ablative erbium-doped:yttrium-aluminium-garnet (Er:YAG) laser on vaginal atrophy induced by iatrogenic menopause in the ewe. Design: Animal experimental, randomised, sham and estrogen-treatment controlled study with blinding for primary outcome. Setting: KU Leuven, Belgium. Sample: Twenty-four ewes. Methods: Menopause was surgically induced, after which the ewes were randomised to three groups receiving vaginal Er:YAG laser application three times, with a 1-month interval; three sham manipulations with a 1-month interval; or estrogen replacement and sham manipulations. At given intervals, ewes were clinically examined and vaginal wall biopsies were taken. Vaginal compliance was determined by passive biomechanical testing from explants taken at autopsy. Main outcome measures: Vaginal epithelial thickness (primary), composition of the lamina propria (collagen, elastin, glycogen and vessel content), vaginal compliance, clinical signs. Results: Animals exposed to Er:YAG laser application and sham manipulation, but not to estrogens, displayed a significant and comparable increase in vaginal epithelial thickness between baseline and 7 days after the third application (69% and 67%, respectively, both P < 0.0008). In laser-treated ewes, temporary vaginal discharge and limited thermal injury were observed. Estrogen-substituted ewes displayed a more prominent increase in epithelial thickness (202%; P < 0.0001) and higher vaginal compliance (P < 0.05). None of the interventions induced changes in the lamina propria. Conclusions: Vaginal Er:YAG laser has comparable effect to sham manipulation in menopausal ewes. Tweetable abstract: Vaginal Er:YAG laser has comparable effect to sham manipulation in menopausal ewes #LASER #GSM #RCT

Supplementary Material for: Comparative Anatomy of the Ovine and Female Pelvis

<p><b><i>Background:</i></b> Pelvic organ prolapse affects half of vaginally parous women. Several animal models are used to study its pathophysiology and treatment. Sheep are interesting because they develop spontaneously prolapse with similar risk factors as women and can be used for vaginal surgery. This study describes ovine pelvis anatomy and compares it to women's pelvis to provide anatomical tools for translational researchers. <b><i>Methods:</i></b> MRI, pelvic dissections, and histology were used for detailed macro- and microscopic analysis of relevant anatomical structures in 6 nulliparous ewes. <b><i>Results:</i></b> Although sheep are quadrupeds, the gross and microscopic anatomies are similar to the female pelvis. Principal differences are the shape and its orientation, the absence of the sacrospinous ligament and the internal obturator. The levator ani (except for the puborectalis) and the coccygeus muscle are present, yet the latter is more developed - coinciding with the tail. The dimensions and morphology of the ovine vagina is comparable. The retropubic and the rectovaginal space are accessible transvaginally. There is a wide expression of estrogen receptors with low or absent immunoreactivity in the urethral epithelium, bladder, anus and internal anal sphincter. <b><i>Conclusion</i></b>: The ovine pelvic floor has many anatomical and ultrastructural similarities to the female pelvic floor.</p