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STAR Protocols Mar 2024Ovariectomy, involving the surgical removal of ovaries, and estradiol replacement facilitate the understanding of sexual dimorphism-related physiological changes,...
Ovariectomy, involving the surgical removal of ovaries, and estradiol replacement facilitate the understanding of sexual dimorphism-related physiological changes, encompassing reproductive biology, metabolism, and hormone-related diseases. In this study, we present a protocol for conducting ovariectomy and estradiol replacement in mice. We describe steps for performing sham and ovariectomy operations, outline preoperative preparations, and provide details on postoperative care, including analgesia administration and the removal of surgical clips. Additionally, we elaborate on the procedures for performing vehicle and estradiol injections. For complete details on the use and execution of this protocol, please refer to Luengo-Mateos et al..
Topics: Female; Humans; Mice; Animals; Estradiol; Ovariectomy; Ovary
PubMed: 38416648
DOI: 10.1016/j.xpro.2024.102910 -
Hypertension (Dallas, Tex. : 1979) May 2024Arterial stiffness is a cardiovascular risk factor and dramatically increases as women transition through menopause. The current study assessed whether a mouse model of...
BACKGROUND
Arterial stiffness is a cardiovascular risk factor and dramatically increases as women transition through menopause. The current study assessed whether a mouse model of menopause increases arterial stiffness in a similar manner to aging and whether activation of the G-protein-coupled estrogen receptor could reverse stiffness.
METHODS
Female C57Bl/6J mice were ovariectomized at 10 weeks of age or aged to 52 weeks, and some mice were treated with G-protein-coupled estrogen receptor agonists.
RESULTS
Ovariectomy and aging increased pulse wave velocity to a similar extent independent of changes in blood pressure. Aging increased carotid wall thickness, while ovariectomy increased material stiffness without altering vascular geometry. RNA-sequencing analysis revealed that ovariectomy downregulated smooth muscle contractile genes. The enantiomerically pure G-protein-coupled estrogen receptor agonist, LNS8801, reversed stiffness in ovariectomy mice to a greater degree than the racemic agonist G-1. In summary, ovariectomy and aging induced arterial stiffening via potentially different mechanisms. Aging was associated with inward remodeling, while ovariectomy-induced material stiffness independent of geometry and a loss of the contractile phenotype.
CONCLUSIONS
This study enhances our understanding of the impact of estrogen loss on vascular health in a murine model and warrants further studies to examine the ability of LNS8801 to improve vascular health in menopausal women.
Topics: Animals; Female; Mice; Aging; Carotid Arteries; Estrogens; GTP-Binding Proteins; Ovariectomy; Pulse Wave Analysis; Receptors, Estrogen; Receptors, G-Protein-Coupled; Vascular Stiffness
PubMed: 38445498
DOI: 10.1161/HYPERTENSIONAHA.123.22024 -
Journal of Applied Physiology... May 2023Female mice have a greater capacity for exercising in the heat than male mice, reaching greater power output and longer times of heat exposure before succumbing to...
Female mice have a greater capacity for exercising in the heat than male mice, reaching greater power output and longer times of heat exposure before succumbing to exertional heat stroke (EHS). Differences in body mass, size, or testosterone do not explain these distinct sex responses. Whether the ovaries could account for the superior exercise capacity in the heat in females remains unknown. Here, we determined the influence of ovariectomy (OVX) on exercise capacity in the heat, thermoregulation, intestinal damage, and heat shock response in a mouse EHS model. We performed bilateral OVX ( = 10) or sham ( = 8) surgeries in young adult (4 mo) female C57/BL6J mice. Upon recovery from surgeries, mice exercised on a forced wheel placed inside an environmental chamber set at 37.5 °C and 40% relative humidity until experiencing loss of consciousness (LOC). Terminal experiments were performed 3 h after LOC. OVX increased body mass by the time of EHS (sham = 3.8 ± 1.1, OVX = 8.3 ± 3.2 g, < 0.05), resulted in shorter running distance (sham = 753 ± 189, OVX = 490 ± 87 m, < 0.05), and shorter time to LOC (sham = 126.3 ± 21, OVX = 99.1 ± 19.8 min, < 0.05). Histopathological assessment of the intestines revealed damage in the jejunum (sham = 0.2 ± 0.7, OVX = 2.1 ± 1.7 AU, < 0.05) and ileum (sham = 0.3 ± 0.5, OVX = 1.8 ± 1.4 AU, < 0.05). OVX increased mesenteric microvascular density (sham = 101 ± 25, OVX = 156 ± 66 10 mm/mm, < 0.05) and decreased concentration of circulatory heat shock protein 72 (HSP72) (sham = 26.7 ± 15.8, OVX = 10.3 ± 4.6 ng/mL, < 0.05). No differences were observed in cytokines or chemokines between groups. Our findings indicate that OVX aggravates the pathophysiological response to EHS in mice. Females outperform males in a mouse model of exertional heat stroke (EHS). Here, we show for the first time the impact of ovariectomy (OVX) on EHS pathophysiology. OVX resulted in a shorter exercise capacity in the heat, greater intestinal damage, and lower heat shock response following EHS.
Topics: Humans; Mice; Male; Female; Animals; Heat Stroke; Cytokines; Ovariectomy
PubMed: 37022961
DOI: 10.1152/japplphysiol.00092.2023 -
Acta Neurobiologiae Experimentalis 2021Advanced glycation end products (AGEs) have been reported to cause neurodegeneration, senile plaque formation and spatial learning and memory deficits. There is much...
Advanced glycation end products (AGEs) have been reported to cause neurodegeneration, senile plaque formation and spatial learning and memory deficits. There is much evidence describing the beneficial effects of aminoguanidine (AG) on the central nervous system; AG is able to inhibit the receptor for AGEs and beta-amyloid (Aβ) deposition in the brain, thus preventing cognitive decline and neurodegeneration. In this study, we investigated whether AG protects against ovariectomy-induced neuronal deficits and Aβ deposition in rats. Animals in the ovariectomy group (OVX) group, and those in the OVX+AG group were treated with AG (100 mg/kg/day) for 8 weeks. Learning and memory were evaluated using the electric Y maze. AGE and Aβ biochemical assessments were performed using enzyme-linked immunosorbent assay (ELISA) kits. Furthermore, evaluations of brain amyloid precursor protein 695 (APP) mRNA expression by RT-PCR and AGE expression by immunohistochemistry were carried out. Ovariectomized rats exhibited memory impairment and Aβ production disorder with upregulated APP mRNA and AGE expression levels. AG pretreatment relieved the ovariectomy-induced learning and memory disorder and significantly ameliorated the Aβ production disturbance and AGE generation. Additionally, pathological changes in morphology were also significantly recovered. Our data reveal that AG plays a potentially neuroprotective role against ovariectomy-induced learning and cognitive impairment and Aβ production disorder. Advanced glycation end products (AGEs) have been reported to cause neurodegeneration, senile plaque formation and spatial learning and memory deficits. There is much evidence describing the beneficial effects of aminoguanidine (AG) on the central nervous system; AG is able to inhibit the receptor for AGEs and beta-amyloid (Aβ) deposition in the brain, thus preventing cognitive decline and neurodegeneration. In this study, we investigated whether AG protects against ovariectomy-induced neuronal deficits and Aβ deposition in rats. Animals in the ovariectomy group (OVX) group, and those in the OVX+AG group were treated with AG (100 mg/kg/day) for 8 weeks. Learning and memory were evaluated using the electric Y maze. AGE and Aβ biochemical assessments were performed using enzyme-linked immunosorbent assay (ELISA) kits. Furthermore, evaluations of brain amyloid precursor protein 695 (APP) mRNA expression by RT-PCR and AGE expression by immunohistochemistry were carried out. Ovariectomized rats exhibited memory impairment and Aβ production disorder with upregulated APP mRNA and AGE expression levels. AG pretreatment relieved the ovariectomy-induced learning and memory disorder and significantly ameliorated the Aβ production disturbance and AGE generation. Additionally, pathological changes in morphology were also significantly recovered. Our data reveal that AG plays a potentially neuroprotective role against ovariectomy-induced learning and cognitive impairment and Aβ production disorder.
Topics: Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Animals; Brain; Cognitive Dysfunction; Guanidines; Memory; Memory Disorders; Neurons; Ovariectomy; Rats
PubMed: 33949165
DOI: 10.21307/ane-2021-002 -
Aging Feb 2021Vulvovaginal atrophy (VVA) is a common menopause-related symptom affecting more than 50% of midlife and older women and cancer patients whose ovarian function are lost...
Vulvovaginal atrophy (VVA) is a common menopause-related symptom affecting more than 50% of midlife and older women and cancer patients whose ovarian function are lost or damaged. Regardless of estrogen deficiency, whether other factors such as the gut microbiota play role in VVA have not been thoroughly investigated. To this end, we performed ovariectomy on 12-weeks' old mice and follow-up at 4 weeks after ovariectomy, and observed atrophied vagina and an altered gut microbiota in ovariectomized mice.. We further performed fecal microbiota transplantation with feces from another cohort of ovary-intact fecund female mice to the ovariectomized ones, and found that the vaginal epithelial atrophy was significantly alleviated as well as the gut microbiota was pointedly changed. All these results suggest that ovarian activity has some influence on the gut microbiota, and the latter from the ovary-intact female mice can somehow make the vagina of mice deficient in ovarian function healthier maybe by up-expressing ESR1 in vaginal cells and enhancing regeneration in vagina. This kind of association between gut microbiota and vaginal health need further exploration such that it may provide an alternative treatment by modulating gut microbiota in patients suffering from VVA but may be reluctant to hormone therapy.
Topics: Animals; Atrophy; Fecal Microbiota Transplantation; Female; Gastrointestinal Microbiome; Mice; Mice, Inbred C57BL; Ovariectomy; RNA, Ribosomal, 16S; Vagina
PubMed: 33658399
DOI: 10.18632/aging.202627 -
PloS One 2022Decline of ovarian function in menopausal women increases metabolic disease risk. Curcuma comosa extract and its major compound,...
Decline of ovarian function in menopausal women increases metabolic disease risk. Curcuma comosa extract and its major compound, (3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol (DPHD), improved estrogen-deficient ovariectomized (OVX) rat metabolic disturbances. However, information on their effects on metabolites is limited. Here, we investigated the impacts of C. comosa ethanol extract and DPHD on 12-week-old OVX rat metabolic disturbances, emphasizing the less hydrophobic metabolites. Metabolomics analysis of OVX rat serum showed a marked increase compared to sham-operated rat (SHAM) in levels of lysophosphatidylcholines (lysoPCs), particularly lysoPC (18:0) and lysoPC (16:0), and of arachidonic acid (AA), metabolites associated with inflammation. OVX rat elevated lysoPCs and AA levels reverted to SHAM levels following treatments with C. comosa ethanol extract and DPHD. Overall, our studies demonstrate the effect of C. comosa extract in ameliorating the metabolic disturbances caused by ovariectomy, and the elevated levels of bioactive lipid metabolites, lysoPCs and AA, may serve as potential biomarkers of menopausal metabolic disturbances.
Topics: Animals; Curcuma; Ethanol; Female; Humans; Lysophosphatidylcholines; Ovariectomy; Phytoestrogens; Plant Extracts; Rats
PubMed: 35588422
DOI: 10.1371/journal.pone.0268179 -
Biomedicine & Pharmacotherapy =... Oct 2023Both estrogen deficiency and aging may lead to osteoporosis. Developing novel drugs for treating osteoporosis is a popular research direction. We screened several...
Both estrogen deficiency and aging may lead to osteoporosis. Developing novel drugs for treating osteoporosis is a popular research direction. We screened several potential therapeutic agents through a new deep learning-based efficacy prediction system (DLEPS) using transcriptional profiles for osteoporosis. DLEPS screening led to a potential novel drug examinee, ataluren, for treating osteoporosis. Ataluren significantly reversed bone loss in ovariectomized mice. Next, ataluren significantly increased human bone marrow-derived mesenchymal stem cell (hBMMSC) osteogenic differentiation without cytotoxicity, indicated by the high expression index of osteogenic differentiation genes (OCN , BGLAP, ALP, COL1A, BMP2, RUNX2). Mechanistically, ataluren exerted its function through the BMP-SMAD pathway. Furthermore, it activated SMAD phosphorylation but osteogenic differentiation was attenuated by BMP2-SMAD inhibitors or small interfering RNA of BMP2. Finally, ataluren significantly reversed bone loss in aged mice. In summary, our findings suggest that the DLEPS-screened ataluren may be a therapeutic agent against osteoporosis by aiding hBMMSC osteogenic differentiation.
Topics: Humans; Female; Animals; Mice; Osteogenesis; Bone Diseases, Metabolic; Osteoporosis; Aging; Ovariectomy
PubMed: 37597324
DOI: 10.1016/j.biopha.2023.115332 -
Stroke Feb 2023There has been a plethora of studies focused on female-specific risk factors and sex differences in stroke published in the past year. This article summarizes several of...
There has been a plethora of studies focused on female-specific risk factors and sex differences in stroke published in the past year. This article summarizes several of those novel studies which provide new knowledge about the field of stroke in women. The Nurses' Health Study II provides new data on the association between laparoscopically proven endometriosis and future stroke, accounting for the mediation effects of hysterectomy and oophorectomy. In a cohort of women from China, the relationship between hysterectomy, oophorectomy, and stroke is further clarified, accounting for the age at which the procedure is performed. The UK Biobank study provides new information on the relationship between oral contraceptive and hormone replacement therapy and stroke, with analytical techniques that focus on the timing of events related to duration of exposure. Finally, 2 new meta-analyses address the question of whether sex differences exist in the presentation of stroke symptoms.
Topics: Female; Humans; Male; Risk Factors; Hysterectomy; Ovariectomy; Contraceptives, Oral; Stroke
PubMed: 36689601
DOI: 10.1161/STROKEAHA.122.041734 -
Gynecologic Oncology Jun 2023Increasing evidence suggests the fallopian tube as the site of origin of BRCA1/2-associated high-grade ovarian cancers. Several ongoing trials are evaluating... (Review)
Review
OBJECTIVE
Increasing evidence suggests the fallopian tube as the site of origin of BRCA1/2-associated high-grade ovarian cancers. Several ongoing trials are evaluating salpingectomy with delayed oophorectomy (RRSDO) for ovarian cancer risk reduction and patients are beginning to ask their clinicians about this surgical option. This study sought to systematically review the available literature examining patient preferences regarding RRSDO and risk-reducing salpingo-oophorectomy (RRSO) to provide clinicians with an understanding of patient values, concerns, and priorities surrounding ovarian cancer risk-reducing surgery.
METHODS
We conducted a systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO No.: CRD42023400690). We searched key electronic databases to identify studies evaluating acceptance and surgical decision-making regarding RRSO and RRSDO among patients with an increased risk of ovarian cancer.
RESULTS
The search yielded 239 results, among which six publications met the systematic review inclusion criteria. Acceptance of RRSDO was evaluated in all studies and ranged from 34% to 71%. Factors positively impacting patients' acceptance of RRSDO included: avoidance of surgical menopause, preservation of fertility, concerns about sexual dysfunction, family history of breast cancer, and avoidance of hormone replacement therapy. Factors limiting this acceptance reported by patients included concerns regarding oncologic safety, surgical timing, and surgical complications.
CONCLUSION
To date, few studies have explored patient perspectives surrounding RRSDO. Collectively, the limited data available indicate a high level of acceptance among BRCA1/2 carriers, and provides insight regarding both facilitating and limiting factors associated with patient preferences to better equip clinicians in the counseling and support of their patients.
Topics: Humans; Female; BRCA1 Protein; BRCA2 Protein; Ovariectomy; Salpingectomy; Ovarian Neoplasms; Breast Neoplasms; Risk Reduction Behavior; Mutation; Genetic Predisposition to Disease
PubMed: 37116391
DOI: 10.1016/j.ygyno.2023.04.006 -
Canadian Journal of Veterinary Research... Oct 2021This study aimed to identify potential biomarkers of canine pyometra and their correlations with clinical parameters. First, 90 dogs with pyometra and 26 healthy female... (Comparative Study)
Comparative Study
This study aimed to identify potential biomarkers of canine pyometra and their correlations with clinical parameters. First, 90 dogs with pyometra and 26 healthy female dogs were compared. Then, paired samples (before and after ovariohysterectomy) from 22 dogs with pyometra and 9 healthy controls from the initial cohort were compared. Concentrations of acute inflammatory proteins, C-reactive protein (CRP) and serum amyloid A (SAA), and cell-free DNA (cfDNA), were significantly higher in dogs with pyometra than in clinically healthy dogs. Cell-free DNA was the most sensitive biomarker for systemic inflammation, based on the receiver operating characteristic curve analysis (area under the curve = 0.959). In addition, cfDNA and CRP were significantly associated with inflammation and organ injury-related clinical parameters. Following the surgical removal of the inflamed uterus, interleukin-6 (IL-6), high-mobility group box 1 (HMGB1), and procalcitonin (PCT) significantly decreased, whereas changes in CRP, SAA, and cfDNA were not significant. These findings indicate that cfDNA, CRP, and SAA are potential clinical biomarkers of systemic inflammation in dogs with pyometra and PCT, IL-6, and HMGB1 are potential biomarkers of clinical recovery.
Topics: Animals; Biomarkers; C-Reactive Protein; Case-Control Studies; Cell-Free Nucleic Acids; Cohort Studies; Dog Diseases; Dogs; Female; Hysterectomy; Inflammation; Ovariectomy; Pyometra; ROC Curve; Serum Amyloid A Protein
PubMed: 34602731
DOI: No ID Found