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BMC Veterinary Research Sep 2023Aldosterone represents an important target of heart failure therapy and may be a valuable indicator of the renin-angiotensin-aldosterone system activity. However, its...
BACKGROUND
Aldosterone represents an important target of heart failure therapy and may be a valuable indicator of the renin-angiotensin-aldosterone system activity. However, its assessment might be challenging because of the effect of individual factors. In a recent study, intact female dogs showed the highest value of urinary aldosterone-to-creatinine ratio (UAldo:C) compared to other sex categories. In humans and rodents, an influence of progesterone has been reported by several studies. To our knowledge, the relationship between aldosterone and progesterone has not yet been investigated in dogs. The aim of this prospective study was to investigate this relationship in sexually intact Chihuahua females, measuring both hormones twice in the same bitch, that is in anoestrus when progesterone concentrations are baseline and in dioestrus when they are high.
RESULTS
The study population consisted of 14 sexually intact Chihuahua bitches. Serum progesterone (34.06 (21.17-44.90) vs. 0.19 [0.13-0.38] ng/ml; P < 0.001) and urinary aldosterone (9886.98 ± 5735.22 vs. 5005.72 ± 2127.73 pg/ml; P = 0.01) were significantly higher in dioestrus compared to anoestrous. Urinary aldosterone-to-creatinine ratio was higher in dioestrus compared to anoestrus (4.16 [3.17-6.80] vs. 3.39 ± 1.64 µg/g), but it did not reach the statistical significance (P = 0.056). Serum progesterone showed a moderate positive correlation with urinary aldosterone (ρ = 0.638, P < 0.001) and UAldo:C (ρ = 0.516, P = 0.005).
CONCLUSIONS
The results of the present study suggest the existence of a progesterone-aldosterone relationship in canine species, indicating that sex and phase of reproductive cycle should be taken into account when interpreting aldosterone concentrations. Further studies are needed to confirm these results on a larger canine population and to identify the underlying mechanisms in this species.
Topics: Humans; Animals; Dogs; Female; Aldosterone; Progesterone; Creatinine; Prospective Studies; Diuretics; Anti-Arrhythmia Agents; Cardiotonic Agents
PubMed: 37670293
DOI: 10.1186/s12917-023-03704-2 -
Scientific Reports Feb 2023The present study aimed to investigate whether time-restricted feeding (TRF) ameliorates metabolic and reproductive phenotypes in a letrozole-induced mouse model of...
The present study aimed to investigate whether time-restricted feeding (TRF) ameliorates metabolic and reproductive phenotypes in a letrozole-induced mouse model of polycystic ovary syndrome (PCOS). Sixty female C57BL/6 N mice were randomly divided into two groups according to the type of food received: either a chow or a 60% high-fat diet. Those mice were subcutaneously implanted with letrozole or placebo pellets at four weeks of age. Then, letrozole-treated mice were randomly assigned to different feeding regimens: (1) TRF for 4 h (ZT12-ZT16) or (2) ad libitum diet. After 4 weeks of dietary intervention, estrous cycles were determined with daily vaginal smear examination, and serial tail-tip blood sampling was performed at 5-min intervals for 2 h to measure the luteinizing hormone (LH) pulse frequency, amplitude, and mean LH levels in the diestrus cycle stage. Letrozole-treated mice in the ad libitum group demonstrated multiple PCOS-like phenotypes including ovulatory dysfunction, polycystic ovaries, and increased body weight, parametrial fat weight, adipocyte size and inflammation, and higher expression of Cyp17, Cyp19, and Fshr in the ovary, and Kiss1r and Gnrh in the hypothalamus, elevated serum testosterone levels, and more rapid and elevated LH pulsatility, with increased pulse frequency, amplitude, and mean levels in the diestrus stage, compared with the controls. After TRF for 4 weeks, those phenotypes reverted to normal levels in letrozole-treated mice, except the percentage of diestrus cycles indicating the arrest of estrous cycling which did not differ between the TRF and ad libitum groups. Our results demonstrate that TRF has therapeutic effects on the reproductive and metabolic phenotypes of a letrozole-induced mouse model of PCOS.
Topics: Humans; Female; Mice; Animals; Letrozole; Polycystic Ovary Syndrome; Mice, Inbred C57BL; Luteinizing Hormone; Disease Models, Animal
PubMed: 36732546
DOI: 10.1038/s41598-023-28260-5 -
Ecotoxicology and Environmental Safety Jun 20234-Vinylcyclohexene diepoxide (VCD), an industrial occupational health hazard chemical associated with premature ovarian insufficiency (POI) and reproductive failure....
4-Vinylcyclohexene diepoxide (VCD), an industrial occupational health hazard chemical associated with premature ovarian insufficiency (POI) and reproductive failure. Recently, investigators have paid an increasing attention on VCD model of menopause recapitulates the natural, physiological transition through perimenopause to menopause. The current study sought to examining the mechanisms of follicular loss and exploring the effect of the model on systems outside of the ovaries. In this study, 28 days female SD rats were injected with VCD (160 mg/kg) vehicle for 15 consecutive days, euthanized in the diestrus phase approximately 100 days after the onset of treatment. Reproductive system injury, Neuroendocrine, sex hormone levels and receptor were observed, the levels of N6-methyladenosine (m6A) RNA modification and the expression of modulator genes were first measured. The VCD treated rats showing irregular estrous cycles, significantly reduced in the number of primordial follicles, the preantral and antral follicles also decreased significantly, accompanied by the plasma level of FSH increased and anti-Mullerian hormone (AMH) were decreased. The total m6A level was significantly decreased after exposure to VCD. Moreover, ALKBH5-mediated YAP m6A modification changed in VCD - induced premature ovarian insufficiency. These present work provides a new perspective on m6A modification in the VCD-induced POI rat model, which could provide valuable insights into the mechanisms underlying follicle development and finding new therapeutic targets for follicle prematurely exhausted. Also provide novel methodological guidance and endocrine basis to guide research and extend the applications in premature ovarian insufficiency model.
PubMed: 37393819
DOI: 10.1016/j.ecoenv.2023.115192 -
Journal of Feline Medicine and Surgery Nov 2023The aim of this study was to evaluate the expression profile of sex steroid receptors and redox mediators in the uterus of domestic cats with pyometra.
OBJECTIVES
The aim of this study was to evaluate the expression profile of sex steroid receptors and redox mediators in the uterus of domestic cats with pyometra.
METHODS
Twelve cats were used and divided into groups: (1) non-gestational healthy diestrus (n = 7) and (2) pyometra (n = 5). The plasma profiles of estradiol and progesterone (P) as well as uterine expression levels of estradiol alpha (ERα), progesterone (PR) and androgen (AR) receptors, of the antioxidant enzymes superoxide dismutase 1 (SOD1), catalase and glutathione peroxidase 1 (GPX1), and of the oxidative damage marker 8-hydroxy-2'-deoxyguanosine (8-OHdG) were evaluated.
RESULTS
Cats with pyometra showed higher plasma P levels and increased uterine messenger RNA (mRNA) and protein expression of ERα and PR, mainly in the glandular epithelium for ERα and in stromal and myometrial cells for PR. In addition, there was an increase in 8-OHdG immunostaining and GPX1 mRNA and protein expression in cats with pyometra compared with those in non-gestational diestrus, while catalase showed a reduction in endometrial immunostaining in cats with pyometra. There were no differences in uterine AR and SOD1 expression between the groups.
CONCLUSION AND RELEVANCE
The findings of this study showed that pyometra is associated with oxidative stress in the uterus of domestic cats and alterations of the profile of sex steroid receptors, especially ERα and PR, and of antioxidant enzymes, suggesting that changes in these mediators may play a role with the etiopathogenesis of this disease.
Topics: Female; Cats; Animals; Receptors, Progesterone; Pyometra; Progesterone; Catalase; Estrogen Receptor alpha; Antioxidants; Superoxide Dismutase-1; Uterus; Estrogens; Estradiol; Oxidation-Reduction; RNA, Messenger; Cat Diseases
PubMed: 38018511
DOI: 10.1177/1098612X231170159 -
Toxicological Sciences : An Official... Oct 2021Di-isononyl phthalate (DiNP) is a high-molecular-weight phthalate commonly used as a plasticizer for polyvinyl chloride and other end products, such as medical devices...
Di-isononyl phthalate (DiNP) is a high-molecular-weight phthalate commonly used as a plasticizer for polyvinyl chloride and other end products, such as medical devices and construction materials. Most of our initial exposure to DiNP occurs by ingestion of DiNP-contaminated foods. However, little is known about the effects of DiNP on the colon. Therefore, the goal of this study was to test the hypothesis that DiNP exposure alters immune responses and impacts specialized epithelial cells in the colon. To test this hypothesis, adult female mice were orally dosed with corn-oil vehicle control or doses of DiNP ranging from 20 µg/kg/d to 200 mg/kg/d for 10-14 days. After the dosing period, mice were euthanized in diestrus, and colon tissues and sera were collected for histological, genomic, and proteomic analysis of various immune factors and specialized epithelial cells. Subacute exposure to DiNP significantly increased protein levels of Ki67 and MUC2, expression of a Paneth cell marker (Lyz1), and estradiol levels in sera compared with control. Gene expression of mucins (Muc1, Muc2, Muc3a, and Muc4), Toll-like receptors (Tlr4 and Tlr5), and specialized epithelial cells (ChgA, Lgr5, Cd24a, and Vil1) were not significantly different between treatment groups and control. Cytokine levels of IL-1RA and CXCL12 were also not significantly different between DiNP treatment groups and control. These data reveal that DiNP exposure increases circulating estradiol levels and gene expression in specialized epithelial cells with immune response capabilities (eg, goblet and Paneth cells) in the mouse colon, which may initiate immune responses to prevent further damage in the colon.
Topics: Animals; Colon; Diethylhexyl Phthalate; Epithelial Cells; Female; Mice; Phthalic Acids; Proteomics
PubMed: 34453847
DOI: 10.1093/toxsci/kfab105 -
Reproduction in Domestic Animals =... Oct 2022In this study, uterine blood flow area (BFA) has been evaluated for the first time using power Doppler ultrasound (PD) as a marker of endometritis in mares and jennies....
In this study, uterine blood flow area (BFA) has been evaluated for the first time using power Doppler ultrasound (PD) as a marker of endometritis in mares and jennies. The uterine BFA in healthy mares was greater in oestrus than in diestrus (p < .001). However, differences in endometrial blood flow between oestrus and diestrus were not observed in mares with endometritis. The uterine blood flow in healthy jennies is not affected by the oestrus cycle. Both species showed an increase in endometrial BFA in pathological uterine conditions compared to controls. BFA was a good marker of endometritis with an area under curve (AUC) (estrus:0.94 (p < .001) diestrus:0.98 (p < .001) in mares and AUC (0.91 (p < .0001) in jennies. The results of this preliminary study suggest that PD ultrasound in combination with computerized image analysis has the potential to be a very useful tool in the diagnosis of endometritis.
Topics: Animals; Endometritis; Endometrium; Equidae; Female; Horse Diseases; Horses; Uterus
PubMed: 35467047
DOI: 10.1111/rda.14132 -
Translational Research : the Journal of... Aug 2021Nociception and opioid antinociception in females are pliable processes, varying qualitatively and quantitatively over the reproductive cycle. Spinal estrogenic... (Review)
Review
Nociception and opioid antinociception in females are pliable processes, varying qualitatively and quantitatively over the reproductive cycle. Spinal estrogenic signaling via membrane estrogen receptors (mERs), in combination with multiple other signaling molecules [spinal dynorphin, kappa-opioid receptors (KOR), glutamate and metabotropic glutamate receptor 1 (mGluR)], appears to function as a master coordinator, parsing functionality between pronociception and antinociception. This provides a window into pharmacologically accessing intrinsic opioid analgesic/anti-allodynic systems. In diestrus, membrane estrogen receptor alpha (mERα) signals via mGluR to suppress spinal endomorphin 2 (EM2) analgesia. Strikingly, in the absence of exogenous opioids, interfering with this suppression in a chronic pain model elicits opioid anti-allodynia, revealing contributions of endogenous opioid(s). In proestrus, robust spinal EM2 analgesia is manifest but this requires spinal dynorphin/KOR and glutamate-activated mGluR. Furthermore, spinal mGluR blockade in a proestrus chronic pain animal (eliminating spinal EM2 analgesia) exacerbates mechanical allodynia, revealing tempering by endogenous opioid(s). A complex containing mu-opioid receptor, KOR, aromatase, mGluRs, and mERα are foundational to eliciting endogenous opioid anti-allodynia. Aromatase-mERα oligomers are also plentiful, in a central nervous system region-specific fashion. These can be independently regulated and allow estrogens to act intracellularly within the same signaling complex in which they are synthesized, explaining asynchronous relationships between circulating estrogens and central nervous system estrogen functionalities. Observations with EM2 highlight the translational relevance of extensively characterizing exogenous responsiveness to endogenous opioids and the neuronal circuits that mediate them along with the multiplicity of estrogenic systems that concomitantly function in phase and out-of-phase with the reproductive cycle.
Topics: Analgesia; Analgesics; Animals; Central Nervous System; Chronic Pain; Estrogens; Female; Glutamates; Humans; Male; Models, Neurological; Nociception; Opioid Peptides; Receptors, Estrogen; Receptors, Glutamate; Receptors, Opioid; Translational Research, Biomedical
PubMed: 33567346
DOI: 10.1016/j.trsl.2021.02.002 -
Frontiers in Immunology 2017Sexual bias is a hallmark in various diseases. This review evaluates sexual dimorphism in clinical and experimental coxsackievirus B3 (CVB3) myocarditis, and how sex... (Review)
Review
Sexual bias is a hallmark in various diseases. This review evaluates sexual dimorphism in clinical and experimental coxsackievirus B3 (CVB3) myocarditis, and how sex bias in the experimental disease changes with increased age. Coxsackieviruses are major causes of viral myocarditis, an inflammation of the heart muscle, which is more frequent and severe in men than women. Young male mice infected with CVB3 develop heart-specific autoimmunity and severe myocarditis. Females infected during estrus (high estradiol) develop T-regulatory cells and when infected during diestrus (low estradiol) develop autoimmunity similar to males. During estrus, protection depends on estrogen receptor alpha (ERα), which promotes type I interferon, activation of natural killer/natural killer T cells and suppressor cell responses. Estrogen receptor beta has opposing effects to ERα and supports pro-inflammatory immunity. However, the sexual dimorphism of the disease is significantly ameliorated in aged animals when old females become as susceptible as males. This correlates to a selective loss of the ERα that is required for immunosuppression. Therefore, sex-associated hormones control susceptibility in the virus-mediated disease, but their impact can alter with the age and physiological stage of the individual.
PubMed: 29201031
DOI: 10.3389/fimmu.2017.01585 -
Scientific Reports Nov 2023Despite the prevalent expression of freezing behavior following Pavlovian fear conditioning, a growing body of literature suggests potential sex differences in defensive...
Despite the prevalent expression of freezing behavior following Pavlovian fear conditioning, a growing body of literature suggests potential sex differences in defensive responses. Our study investigated how female defensive behaviors are expressed in different threat situations and modulated by the estrous cycle. We aimed to compare freezing and flight-like responses during the acquisition and retrieval of fear conditioning using two distinct unconditioned stimuli (US) in two different spatial configurations: (1) electrical footshock (FUS) in a small, conventional enclosure with a grid floor, and (2) a predator-like robot (PUS) in a spacious, open arena. Fear conditioning with FUS showed no substantial differences between male and female rats of two different estrous cycles (proestrus and diestrus) in the levels of freezing and flight. However, when PUS was employed, proestrus female rats showed significantly more flight responses to the CS during both acquisition and the retrieval compared to the male and diestrus female rats. Taken together, our findings suggest that hormonal influences on the choice of defensive strategies in threat situations are significantly modulated by both the type of US and the spatial configuration of the environment.
Topics: Rats; Female; Male; Animals; Conditioning, Classical; Estrous Cycle; Fear; Proestrus; Behavior, Animal
PubMed: 38017045
DOI: 10.1038/s41598-023-47591-x -
British Journal of Pharmacology Jan 2023Kcnq-encoded K 7 channels (termed K 7.1-5) regulate vascular smooth muscle cell (VSMC) contractility at rest and as targets of receptor-mediated responses. However, the...
BACKGROUND AND PURPOSE
Kcnq-encoded K 7 channels (termed K 7.1-5) regulate vascular smooth muscle cell (VSMC) contractility at rest and as targets of receptor-mediated responses. However, the current data are mostly derived from males. Considering the known effects of sex, the oestrous cycle and sex hormones on vascular reactivity, here we have characterised the molecular and functional properties of K 7 channels from renal and mesenteric arteries from female Wistar rats separated into di-oestrus and met-oestrus (F-D/M) and pro-oestrus and oestrus (F-P/E).
EXPERIMENTAL APPROACH
RT-qPCR, immunocytochemistry, proximity ligation assay and wire myography were performed in renal and mesenteric arteries. Circulating sex hormone concentrations were determined by liquid chromatography-tandem mass spectrometry. Whole-cell electrophysiology was undertaken on cells expressing K 7.4 channels in association with G-protein-coupled oestrogen receptor 1 (GPER1).
KEY RESULTS
The K 7.2-5 activators S-1 and ML213 and the pan-K 7 inhibitor linopirdine were more effective in arteries from F-D/M compared with F-P/E animals. In VSMCs isolated from F-P/E rats, exploratory evidence indicates reduced membrane abundance of K 7.4 but not K 7.1, K 7.5 and Kcne4 when compared with cells from F-D/M. Plasma oestradiol was higher in F-P/E compared with F-D/M, and progesterone showed the converse pattern. Oestradiol/GPER1 agonist G-1 diminished K 7.4 encoded currents and ML213 relaxations and reduced the membrane abundance of K 7.4 and interaction between K 7.4 and heat shock protein 90 (HSP90), in arteries from F-D/M but not F-P/E.
CONCLUSIONS AND IMPLICATIONS
GPER1 signalling decreased K 7.4 membrane abundance in conjunction with diminished interaction with HSP90, giving rise to a 'pro-contractile state'.
Topics: Male; Rats; Female; Animals; Rats, Wistar; Mesenteric Arteries; Myocytes, Smooth Muscle; Myography; Estradiol
PubMed: 36085551
DOI: 10.1111/bph.15947