Intact Females Research Articles

Sex-related response in mice after sub-acute intraperitoneal exposure to silver nanoparticles

Silver nanoparticles (AgNPs) are among the most commercialized nanomaterials in biomedicine due to their antimicrobial and anti-inflammatory properties. Nevertheless, possible health hazards of exposure to AgNPs are yet to be understood and therefore raise public concern in regards of their safety.In this study, sex-related differences, role of steroidal hormones and influence of two different surface stabilizing agents (polymer vs. protein) on distribution and adverse effects of AgNPs were investigated in vivo. Intact and gonadectomised male and female mice were treated with seven AgNPs doses administered intraperitoneally during 21 days. After treatment, steroid hormone levels in serum, accumulation of Ag levels and oxidative stress biomarkers in liver, kidneys, brain and lungs were determined.Sex-related differences were observed in almost all tissues. Concentration of Ag was significantly higher in the liver of females compared to males. No significant difference was found for AgNP accumulation in lungs between females and males, while the lungs of intact males showed significantly higher Ag accumulation compared to gonadectomised group. Effect of surface coating was also observed, as Ag accumulation was significantly higher in kidneys and liver of intact females, as well as in kidneys and brain of intact males treated with protein-coated AgNPs compared to polymeric AgNPs. Oxidative stress response to AgNPs was the most pronounced in kidneys where protein-coated AgNPs induced stronger effects compared to polymeric AgNPs. Interestingly, protein-coated AgNPs reduced generation of reactive oxygen species in brains of females and gonadectomised males. Although there were no significant differences in levels of hormones in the AgNP-exposed animals compared to controls, sex-related differences in oxidative stress parameters were observed in all organs.Results of this study highlight the importance of including the sex-related differences and effects of protein corona in biosafety evaluation of AgNPs exposure.

Phlpp1 is induced by estrogen in osteoclasts and its loss in Ctsk-expressing cells does not protect against ovariectomy-induced bone loss.

Prior studies demonstrated that deletion of the protein phosphatase Phlpp1 in Ctsk-Cre expressing cells enhances bone mass, characterized by diminished osteoclast activity and increased coupling to bone formation. Due to non-specific expression of Ctsk-Cre, the definitive mechanism for this observation was unclear. To further define the role of bone resorbing osteoclasts, we performed ovariectomy (Ovx) and Sham surgeries on Phlpp1 cKOCtsk and WT mice. Micro-CT analyses confirmed enhanced bone mass of Phlpp1 cKOCtsk Sham females. In contrast, Ovx induced bone loss in both groups, with no difference between Phlpp1 cKOCtsk and WT mice. Histomorphometry demonstrated that Ovx mice lacked differences in osteoclasts per bone surface, suggesting that estradiol (E2) is required for Phlpp1 deficiency to have an effect. We performed high throughput unbiased transcriptional profiling of Phlpp1 cKOCtsk osteoclasts and identified 290 differentially expressed genes. By cross-referencing these differentially expressed genes with all estrogen response element (ERE) containing genes, we identified IGFBP4 as potential estrogen-dependent target of Phlpp1. E2 induced PHLPP1 expression, but reduced IGFBP4 levels. Moreover, genetic deletion or chemical inhibition of Phlpp1 was correlated with IGFBP4 levels. We then assessed IGFBP4 expression by osteoclasts in vivo within intact 12-week-old females. Modest IGFBP4 immunohistochemical staining of TRAP+ osteoclasts within WT females was observed. In contrast, TRAP+ bone lining cells within intact Phlpp1 cKOCtsk females robustly expressed IGFBP4, but levels were diminished within TRAP+ bone lining cells following Ovx. These results demonstrate that effects of Phlpp1 conditional deficiency are lost following Ovx, potentially due to estrogen-dependent regulation of IGFBP4.

G protein-coupled estrogen receptor 1: a novel target to treat cardiovascular disease in a sex-specific manner?

As an agonist of the classical nuclear receptors, estrogen receptor-α and -β (NR3A1/2), estrogen has been assumed to inhibit the development of cardiovascular disease in premenopausal women. Indeed, reduced levels of estrogen after menopause are believed to contribute to accelerated morbidity and mortality rates in women. However, estrogen replacement therapy has variable effects on cardiovascular risk in postmenopausal women, including increased serious adverse events. Interestingly, preclinical studies have shown that selective activation of the novel membrane-associated G protein-coupled estrogen receptor, GPER, can promote cardiovascular protection. These benefits are more evident in ovariectomised than intact females or in males. It is therefore possible that selective targeting of the GPER in postmenopausal women could provide cardiovascular protection with fewer adverse effects that are caused by conventional 'receptor non-specific' estrogen replacement therapy. This review describes new data regarding the merits of targeting GPER to treat cardiovascular disease with a focus on sex differences.

Evaluation of the ability of haemodynamic variables obtained with minimally invasive techniques to assess fluid responsiveness in endotoxaemic Beagles

ObjectiveTo examine the ability of different haemodynamic variables recorded by minimally invasive monitoring techniques to assess fluid responsiveness (FR) in endotoxaemic Beagles. Study designProspective terminal experimental study. AnimalsA group of six healthy, purpose-bred Beagle dogs (three intact females and males), age 5–9.8 years (range) and weighing 11.4–17.9 kg. MethodsEndotoxaemic shock was induced by injecting 1 mg kg–1Escherichia coli lipopolysaccharide (LPS) intravenously in six sevoflurane-anaesthetized mechanically ventilated Beagles for another project. After 10 minutes, three Ringer’s acetate boluses (10 mL kg–1) were administered each over 10 minutes with collection of haemodynamic data immediately before and after each bolus. Thereafter, arterial hypotension was treated with noradrenaline ± dexmedetomidine until arterial pressures increased to a target value. After a wash-out period of 20 minutes another three boluses of fluid were administered and measurements were repeated equally. For each fluid bolus, FR was considered positive when change (Δ) in stroke volume measured by pulmonary artery thermodilution was ≥15%. To test predictive accuracy for FR, we recorded heart rate, invasive arterial, right atrial and pulmonary capillary wedge pressures, pulse wave transit time with haemodynamic monitors, calculated pulse pressure, shock index and rate over pressure evaluation (ROPE) and measured stroke distance and corrected flow time (FTc) with oesophageal Doppler monitoring. ResultsA total of 35 measurements (19 positive and 16 negative responses) were evaluated. A FTc < 330 ms, Δ pulse pressure ≥20%, Δ shock index ≤–14% and ΔROPE ≤–17% were the most significant indicators of positive FR with an area under the receiver operating characteristics curve between 0.72 and 0.74. Conclusions and clinical relevanceIn endotoxaemic Beagles, none of the assessed haemodynamic variables could predict FR with high sensitivity and specificity.

Репродуктивна токсичність тріазолових фунгіцидів ципроконазолу і епоксиконазолу при дії на самців і самиць щурів wistar у період гаметогенезу

Aim. Studying the effect of generic pesticides cyproconazole (98 %) and two samples of epoxiconazole (epoxiconazole 1 — 95,75 % and epoxiconazole 2 — 98,7 %) on the reproductive system of male and female Wistar Han rats at the level of the organism when exposed during gametogenesis, identification and characterization of their hazard, as well as assessment of the risk of reproductive toxicity of these compounds. Materials and Methods. The test samples were administered daily (5 days a week) by oral gavage at doses of 0.2 and 2.0 mg/kg for cyproconazole and 0.5 and 2.0 mg/kg for epoxiconazoles during 11 weeks for males, and 10 weeks for females. Also, there were kept intact males and females, intended for crossover mating with experimental animals. After the end of the exposure, functional indicators of the state of the gonads and the ability of animals to reproduce offspring were studied. The duration and the frequency of each stage of the estrous cycle in female rats and the number of motile sperm, the total amount of sperm and the number of abnormal forms of germ cells of the male rats were studied. The reproductive function state in females was evaluated on day 20th of pregnancy. Thereby the number of corpora lutea in the ovaries, number of alive, dead and resorbed foetuses and embryos, the foetus weight, total weight of litters were registered. The studies were carried out in accordance with the recommendations of the Bioethics Commission and the Centre’s standard operating procedures, developed in accordance with the recommendations and requirements of Good Laboratory Practice (GLP). Conclusions. Test substances at a maximum dose of 2.0 mg/kg of body weight have reproductive toxicity and endocrine-disruptive effect, exerting a significant antiandrogenic effect on males and antiestrogenic effect on female rats. No-observed-adverse-effect-level (NOАEL) for gonadal and reproductive toxicity for male and female Wistar Han rats were established. They are 0.2 mg/kg body weight for cyproconazole and 0.5 mg/kg body weight for epoxiconazole. Key Words: azole fungicides, cyproconazole, epoxiconazole, reproductive toxicity, antiandrogenic and antiestrogenic effects, Wistar Han rats.

Comorbidity affects Вcl-2 levels in mitochondria in C57BL/6 mice with transplantable B16/F10 melanoma.

e21581 Background: Overexpression of the Bcl-2 protein inhibits apoptosis and promotes carcinogenesis. Stress causes signaling leading to cell buffering with Bcl-2 protein above acceptable levels. The purpose of the study was to analyze the influence of comorbidity – chronic neurogenic pain (CNP) – on the Bcl-2 levels in mitochondria of cells of melanoma, the heart, skin and brain in female mice with growing tumors. Methods: Female С57ВL/6 mice were divided into groups: intact group (n = 21); control group with a CNP model – bilateral sciatic nerve ligation (n = 21); group M – B16/F10 melanoma (n = 63); CNP+M group – B16/F10 melanoma was transplanted 3 weeks after the CNP model creation (n = 63). The concentration of Bcl-2 (ng/mg of protein) was determined in mitochondrial samples by ELISA (Thermo Fisher Scientific, Austria). Statictical analysis of results: Statistica 10.0. Results: CNP decreased the Bcl-2 level in heart mitochondria by 1.3 times (p &lt; 0.05), but increased it in skin and brain mitochondria by 5.8 and 1.3 times, respectively. Similar changes were observed in melanoma growth 1 week after its transplantation: Bcl-2 levels decreased in heart mitochondria by 1.3 times, and increased in the skin and brain by 8.9 and 1.3 times, respectively. After 2 weeks of the tumor growth, Bcl-2 in brain mitochondria decreased by 1.7 times, and it started declining in the skin by the 3rd week – by 4 times, compared to intact females. Bcl-2 in tumor mitochondria exceeded the values in the skin by more than 4 times throughout the experiment. Tumor growth in presence of CNP caused a decrease in Bcl-2 in brain mitochondria by 2.4 times after 3 weeks, and in the heart and skin – by 2 and 1.7 times, respectively, after 2 weeks. Bcl-2 in tumor mitochondria in presence of CNP was lower than in the intact skin on average by 1.8 times throughout the experiment. Conclusions: CNP as a comorbidity caused a modulating effect on the mechanisms of survival and apoptosis of cells both in the tumor and in the main organs providing the vital functions of the body - the brain and heart, and also affects the target organ of melanoma - the skin. The results demonstrated the ability of comorbidity to change levels of Bcl-2 in mitochondria depending on the stage of tumor development.

Estrogen Receptor β Contributes to Both Hypertension and Hypothalamic Plasticity in a Mouse Model of Peri-Menopause.

Hypertension susceptibility in women increases at the transition to menopause, termed perimenopause, a state characterized by erratic estrogen fluctuation and extended hormone cycles. Elucidating the role of estrogen signaling in the emergence of hypertension during perimenopause has been hindered by animal models that are confounded by abrupt estrogen cessation or effects of aging. In the present study, accelerated ovarian failure (AOF) in estrogen receptor β (ERβ) reporter mice was induced by 4-vinylcyclohexene diepoxide in young mice to model early-stage ovarian failure (peri-AOF) characteristic of peri-menopause. It was found that administering ERβ agonists suppressed elevated blood pressure in a model of neurogenic hypertension induced by angiotensin II (AngII) in peri-AOF, but not in age-matched male mice. It was also found that ERβ agonist administration in peri-AOF females, but not males, suppressed the heightened NMDAR signaling and reactive oxygen production in ERβ neurons in the hypothalamic paraventricular nucleus (PVN), a critical neural regulator of blood pressure. It was further shown that deleting ERβ in the PVN of gonadally intact females produced a phenotype marked by a sensitivity to AngII hypertension. These results suggest that ERβ signaling in the PVN plays an important role in blood pressure regulation in female mice and contributes to hypertension susceptibility in females at an early stage of ovarian failure comparable to human perimenopause.

Tissue‐Specific Differences in Myocardial and Coronary Vascular ACE2 and TMPRSS2 mRNA Levels are Dependent Upon Sex, Comorbidities, Pressure‐Overload, and Pig Species

SARS‐COV‐2, or COVID‐19, is a respiratory virus infecting over 86 million people worldwide. In addition to respiratory infections, SARS‐COV‐2 has been shown to include cardiovascular (CV) complications, including myocarditis and acute coronary syndrome. Risk of severe complications from SARS‐COV‐2 in individuals with existing CV and metabolic disease has been shown to be increased. Evidence indicates SARS‐COV‐2 enters tissues via the angiotensin‐converting enzyme 2 (ACE2) receptor and that the virus is primed and activated by transmembrane protease, serine 2 (TMPRSS2). The goal of this study was to determine ACE2 and TMPRSS2 mRNA levels in pre‐clinical swine models of heart failure (HF). We hypothesized sex, pressure‐overload, and comorbidities would increase ACE2 and TMPRSS2 mRNA levels. A retrospective analysis was conducted in previously completed studies in our lab including: 1) Female, intact Ossabaw swine that were either lean control or western diet‐fed aortic‐banded (N=4‐5/group); 2) Female Yucatan mini‐swine subject to ovariectomy and/or aortic banding (N=5‐8/group); and 3) Sedentary and exercise trained male, intact Yucatan mini‐swine that were aortic banded. ACE2 and TMPRSS2 mRNA levels were evaluated in the left ventricle (LV), right ventricle (RV), and coronary vasculature using qRT‐PCR. Linear regression analysis was used to determine differences between the following variables: pig species, sex hormones, aortic banding, comorbidities, exercise training, and tissue. Data was log‐transformed to meet linear regression assumptions. ACE2 and TMPRSS2 mRNA levels were significantly influenced by sex, comorbidity, and tissue type. TMPRSS2 mRNA levels were also influenced by species and disease status. Specifically, ACE2 mRNA levels decreased 57.1% in the LV and increased 169.9% in the RV of males compared to coronary vessels in intact females. TMPRSS2 mRNA levels increased in the LV and RV of males (1,218.6% and 5,479.8%, respectively) compared to coronary vessels in intact females. ACE2 and TMPRSS2 mRNA levels increased 344% and 453.4%, respectively, in the LV of Ossabaw swine fed a Western Diet compared to coronary vessels from Yucatan and Ossabaw swine without comorbidities. Species differences indicated TMPRSS2 mRNA levels increased 449.2% in the RV and 498.6% in the LV in Yucatan mini‐swine compared to coronary vessels in Ossabaw swine. A 107.3% increase in TMPRSS2 mRNA level was observed in male swine without HF compared to female intact swine with HF highlighting the importance of sex and disease state. Exercise training did not impact ACE2 or TMPRSS2 mRNA levels irrespective of tissue. In conclusion, these results suggest differences in RV, LV and coronary mRNA levels of ACE2 and TMPRSS2 are dependent upon sex and comorbidities. TMPRSS2 levels are additionally influenced by pig species and pressure‐overload. These results provide insight into how ACE2 and TMPRSS2 mRNA levels may influence the cardiovascular involvement of SARS‐COV‐2 infection in an experimental setting of pre‐clinical HF incorporating different swine species, sex, and comorbidities.

Estradiol‐Specific Neural Regulation of Social Stress Susceptibility in Female Rats

Repeated exposure to social stress is a common risk factor for development of anxiety disorders. Women are twice as likely as men to suffer from anxiety. However, this increased susceptibility in females is confined between the onset of puberty and the end of menopause. This suggests that ovarian hormones may contribute to the disproportionate development of stress-related anxiety disorders among women. We have previously shown that witness stress (WS), a model of social stress in which a female rat is subjected to witnessing an aggressive social defeat encounter between a male intruder and a novel male resident, produces anxiety-like behaviors selectively in intact, cycling female rats. Ovariectomized (OVX) females are largely resistant to witness stress. Moreover, intact females exposed to WS exhibit a distinct increase in corticotropin releasing factor (CRF) expression in the CeA. The current study seeks to understand specific 17-β estradiol-induced neural regulation that may contribute to the heightened susceptibility to social stress among females. Following recovery from implantation of an intravenous catheter and OVX or sham surgery, female rats were treated with either 17-β estradiol (17-βE, 10μg/rat, s.c.) or vehicle (veh, 0μg/rat, s.c.). One hour after injection, female rats were exposed to WS or control handling and video-recorded for 15 minutes. Witness stress-evoked burying, freezing, and rearing behaviors were subsequently quantified to assess stress-induced anxiety-like responses. To quantify CRF expression, frozen brains were sliced coronally, immunohistochemistry was conducted, and brains were double labeled for CRF and cfos in various stress-sensitive regions. Behavioral responses showed WS rats spent significantly more time burying compared to control rats. Veh-treated OVX rats were less behaviorally reactive to WS as evidenced by decreased WS-evoked burying durations compared with intact veh-treated witnesses. However, OVX rats treated with 17-βE exhibited WS-induced anxiety-like responses similar to those of intact females as demonstrated by similar stress-evoked burying durations during stress. There was no effect of stress or treatment on freezing or rearing behaviors. Furthermore, cfos positive CRF expression in the CeA was increased for intact WS rats. Analysis of stress sensitive brain regions such as the hippocampus and locus coeruleus are ongoing. Taken together, these finding suggest that 17-βE plays a paramount role in facilitating the anxiety-like behaviors to witness stress and points towards specific neural regulation of these responses. These studies will lay the foundation for identifying pharmacological targets to increase stress resilience.

Serum cross-linked N-telopeptide of type I collagen across the canine life span: An investigation in intact and neutered male and female dogs

In this study, we conducted study to explore the association between serum cross-linked N-telopeptide of type I collagen (NTx), a marker of bone resorption, and age, body weight, and blood biochemical parameters as well as the neutered and intact status in male and female dogs. We targeted 145 healthy dogs (aged 0.33–18.33 years); 70 were males (38 intact, 32 castrated), and 75 were females (31 intact, 44 ovariohysterectomized). We found that the NTx levels were significantly higher in dogs aged ≤2 years than in older dogs. NTx concentration tended to decrease with age in dogs aged ≤2 years, but not significantly, and remained constant in dogs aged >2 years. Accordingly, we investigated sex/sterilization status in two age cohorts (juvenile-to-young-adult, ≤2 years of age; adult-to-geriatric, >2 years of age). In the adult-to-geriatric cohort, NTx concentration was highest in intact males, followed by neutered males, neutered females, and intact females. The intact vs. neutered difference was significant in males, but not in females. Our results suggested that estradiol deficiency may not affect bone metabolism in female dogs, but androgen deficiency may affect bone metabolism in male dogs. Furthermore, age did not affect bone metabolism after 2 years. NTx concentrations were significantly higher in the juvenile-to-young-adult cohort than in the adult-to-geriatric cohort and tended to decrease with age, similar to young humans. This study unveils novel sex differences in canine serum NTx concentrations and suggests the effect of neutering on bone metabolism, showing that serum NTx concentrations change with age.

Onset and duration of action of lokivetmab in a canine model of IL-31 induced pruritus.

BackgroundInterleukin (IL)‐31 is a cytokine involved in allergic inflammation which induces pruritus across species including dogs. Using recombinant canine IL‐31 we have developed a model of pruritus in the dog to evaluate onset of action and duration of effect of therapeutic drugs.ObjectiveTo assess the onset of action and duration of effect of lokivetmab (Cytopoint) in the IL‐31‐induced pruritus model.AnimalsTwenty‐four purpose‐bred beagle dogs (neutered males, spayed and intact females) 1.5–4.7 years old and weighing between 6 and14 kg.Methods and materialsRandomized, blinded, placebo‐controlled studies were designed to evaluate the antipruritic properties of lokivetmab. Laboratory beagle dogs were given either placebo, 0.125, 0.5 or 2.0 mg/kg lokivetmab, subcutaneously. IL‐31 then was administered to evaluate pruritus 3–5 h post‐placebo or ‐lokivetmab administration as well as one, seven, 14, 28, 42 and 56 days post‐dosing. Pruritus was evaluated over a 2 h window in animals by video monitoring and scored using a categorical scoring system.ResultsWhen animals were given 2.0 mg/kg lokivetmab, a significant reduction in pruritus was observed at 3–4, 4–5 and 3–5 h post‐treatment (P ≤ 0.0001). When animals were given either 0.125, 0.5 or 2 mg/kg lokivetmab, the duration of effect was dose‐dependent and statistically significant for 14, 28 and 42 days, respectively (P ≤ 0.0288).ConclusionThese data indicate that a single subcutaneous injection of 2 mg/kg lokivetmab produces a significant suppression of pruritus starting 3 h post‐treatment that can be sustained for 42 days.

17β-Estradiol Is Involved in the Sexual Dimorphism of the Immune Response to Malaria.

Malaria is the leading cause of parasitic infection-related death globally. Additionally, malaria-associated mortality is higher in men than in women, and this sexual dimorphism reflects differences in innate and adaptive immune responses that are influenced by sex hormones. Normally, females develop more robust immune responses against parasites than males. However, most clinical and laboratory studies related to the immune response to malaria do not consider sex as a variable, and relatively few studies have compared the sex-dependent role of 17β-estradiol in this process. In this study, we decreased in vivo the levels of 17β-estradiol by gonadectomy or administered 17β-estradiol to intact or gonadectomized male and female CBA/Ca mice infected with Plasmodium berghei ANKA. Subsequently, we assessed the effects of 17β-estradiol on parasite load; the percentages of different immune cells in the spleen; the plasma levels of antibodies and pro- and anti-inflammatory cytokines; and the mRNA expression levels of cytokine-encoding genes in the brain. The results showed that the administration of 17β-estradiol increased parasitemia and decreased body weight in intact female mice. Moreover, intact females exhibited higher levels of CD8+ T cells and lower levels of NK1.1+ cells than their male counterparts under the same condition. Gonadectomy increased IFN-γ and decreased TNF-α concentrations only in intact female mice. Additionally, IL-10 levels were higher in intact females than in their male counterparts. Finally, the mRNA expression levels of cytokines coding genes in the brain showed a dimorphic pattern, i.e., gonadectomy upregulated Tnf, Il1b, and Il10 expression in males but not in females. Our findings explain the sexual dimorphism in the immune response to malaria, at least in part, and suggest potential sex-dependent implications for the efficacy of vaccines or drugs targeting malaria.

Reproductive performance of Macrobrachium acanthurus (Crustacea, Palaemonidae) females subjected to unilateral eyestalk ablation

AbstractThe present study investigated the effects of eyestalk ablation on the reproductive performance of females from the native caridean shrimp Macrobrachium acanthurus. The reproduction parameters fertility, fecundity, egg volume, larvae size, loss of embryos and number of females with viable eggs/larvae were evaluated. Females presenting carapace length of 12–15 mm and spent stage of gonadal development were divided into two groups, one undergoing unilateral eyestalk ablation and the other remaining intact. The specimens were kept in aquarium until ovarian maturation, then brought together with males for mating (proportion of two females for each male). Fecundity and fertility were greater in intact females (1,741 eggs and 1,045 larvae) than in ablated ones (1,373 eggs and 741 larvae). Ablation also reduced the percentage of females with viable eggs (68% intact versus 49% ablated) and larvae (82% intact versus 64% ablated), besides increasing the loss of embryos. Egg volume and shape (ellipsoid) and larvae size were similar, as was the duration of embryonic development. The results of this study suggest that, although ablated females exhibit a high rate of survival, their reproductive performance is reduced; therefore, the ablation technique is not recommended in M. acanthurus farming, so as to protect the animals from physiological stress.

Occurrence of uroliths - age-, breed-, and gender-specific differences in dogs from Germany

The aim of this study was to assess the distribution and frequency of uroliths in dogs in Germany and to evaluate age-, gender-, and breed-specific differences. A total of 2772 uroliths from dogs in Germany that had been submitted from veterinary practices during the years 2017-2019 were analyzed by infrared spectroscopy. Uroliths were analyzed as follows: Struvite (44.7 %), calcium oxalate monohydrate (whewellite 24.5 %), cystine (15.2 %), ammonium urate (5.3 %), calcium oxalate dihydrate (weddellite 4.4 %), calcium phosphate (1.6 %), xanthine (1.2 %), whewellite/weddellite (11 %), brushite (0.4 %) and other substances (1.7 %). The dogs' median age (in years) with regards to the urolith type amounted to: struvite 8, calcium oxalate (whewellite and weddellite) 10, cystine 5, brushite 11, xanthine 6.5, and ammonium urate 6 years. Struvite uroliths were most common in intact females (83.8 %) and neutered females (80.8 %), while cystine uroliths (36.7 %) and calcium oxalates (35.7 % whewellite and weddellite) were most common in intact males. Calcium oxalate (50 %), struvite (17.3 %), and cystine uroliths (10.5 %) were found in male neutered dogs. The most frequent breeds with struvite uroliths were Pug (75.9 %), Labrador (73.1 %), Shih Tzu (62.2 %), Dachshund (50.4 %) and Maltese (36 %). Calcium oxalates were most frequently encountered in the breeds Miniature Schnauzer (54.8 %), Jack Russell Terrier (49.5 %), and Yorkshire Terrier (48.2 %). Cystine uroliths were most frequent in the breeds French Bulldog (47.2 %), Bulldogs (44.8 %), Chihuahua (44.1 %) and Dachshund (32.8 %). Dogs from Germany displayed age-, gender- and breed-specific differences in the frequency of urine calculi occurrence. Knowledge of the frequent occurrence of the distinct uroliths in Germany as well as potential breed dispositions allow the veterinarian to implement an appropriate preventive treatment plan. This would involve a targeted monitoring program for the prevention and follow-up care of the patient in conjunction with the pet owner.

Homeostatic Regulation of Estrus Cycle of Young Female Mice on Western Diet.

The etiology of reproductive disorders correlates with weight gain in patients, but the link between reproduction, diet, and weight has been difficult to translate in rodents. As rates of childhood obesity and reproductive disorders increase, the need to study the effects of weight and diet on adolescent females is key. Previous studies show that female mice are resistant to high-fat diet–induced weight gain, but the mechanisms are unclear. Literature also suggests that ovarian function is essential to resistance in weight gain, as an ovariectomy leads to a weight-gaining phenotype similar to male mice on a high-fat diet. However, reproductive changes that occur in adolescent mice on high-fat diet have not been assessed. Here, we show that regulation of the estrus cycle via progesterone is critical to metabolic homeostasis in female mice on a high-fat diet. Female mice were put on high-fat diet or control diet for 12 weeks starting at 4 weeks of age. Every 4 weeks, their estrus cycle was tracked and fasting glucose was measured. We found that after 4 weeks on high-fat diet, there was no difference in weight between groups, but an increase in time spent in proestrus and estrus in mice on high-fat diet and an increase in serum progesterone during proestrus. These results show that intact females modulate their estrus cycle in response to a high-fat diet as a mechanism of homeostatic regulation of body weight, protecting them from metabolic abnormalities. Understanding the mechanisms behind this protection may yield therapeutic opportunities for treatment of reproductive disorders in adolescent female patients.

Fitness Implications of Nonlethal Injuries in Scorpions: Females, but Not Males, Pay Reproductive Costs.

AbstractThe ability to detach a body part in response to a predation attempt is known as autotomy, and it is perhaps the most intensively studied form of nonlethal injury in animals. Although autotomy enhances survival, it may impose reproductive costs on both males and females. We experimentally investigated how autotomy affects the reproductive success of males and females of a scorpion species. Individuals of Ananteris balzani autotomize the last abdominal segments (the tail), losing the anus and leading to lifelong constipation, since regeneration does not occur. Although the male tail is used during courtship and sperm transfer, autotomy has no effect on male mating success. The combined effect of increased mortality and reduced fecundity resulted in autotomized females producing nearly 35% fewer offspring than intact females. In conclusion, the negative effects of tail autotomy are clearly sex dependent, probably because the factors that influence reproductive success in males and females are markedly different.

EFFECTS OF CASTRATION ON GROWTH RATE, BODY AND VISCERAL ORGAN WEIGHTS OF PIGS.

Effects of castration on growth rate, body and visceral organ weights of pigs were investi­gated using data from intact males, intact females of Large White pigs full or half cast­rated at 2, 4, or 6 weeks of age. Body weights and feed intake were recorded to the nearest 0.1kg at weekly intervals from birth, while weights of abdominal and thoracic organs were taken at slaughter. Results show that age at castration signi­ficantly affected weaning weights and weights at 2 months of age (P &lt; 0.05), but did not affect the weights of visceral organs and the average daily weight gain (P&gt; 0.05). Castration significantly affected weaning weights (P &lt;0.05) average daily gain (P &lt;0.01), body weights at 4 months (P &lt;0.05), but not the weights of the visceral organs (P&gt; 0.05) Intact females and, intact males significant­ly differed in body weights at 4 months and in average daily weight gain (P 0.05). Com­parisons between full castrates and intact males showed significant differences in all the measured parameters except the weights of visceral organs. Full castrates and intact females did not differ, significantly (P &gt; 0.05) in any of the traits measured.

Effects of a new thyrotropic drug isolated from Potentilla alba on the male reproductive system of rats and offspring development

BackgroundThe dysfunction of the thyroid gland is a common medical condition. Nowadays, patients frequently use medicinal herbs as complementary or alternative options to conventional drug treatments. These patients may benefit from treatment of thyroid dysfunctions with Potentilla alba L. preparations. While it has been reported that Potentilla alba preparations have low toxicity, nothing is known about their ability to affect reproductive functions in patients of childbearing age.MethodsMale Wistar rats were orally treated with a thyrotrophic botanical drug, standardized Potentilla alba Dry Extract (PADE), at doses 8 and 40 times higher than the median therapeutic dose recommended for the clinical trials, for 60 consecutive days. Male Wistar rats receiving water (H2O) were used as controls. After completing treatment, half of the PADE-treated and control males were used to determine PADE gonadotoxicity, and the remaining half of PADE-treated and control males were mated with intact females. Two female rats were housed with one male for two estrus cycles. PADE effects on fertility and fetal/offspring development were evaluated.ResultsHerein, we report that oral treatment of male Wistar rats with PADE before mating with intact females instigated marked effects on male reproductive organs. Treatment significantly decreased the motility of the sperm and increased the number of pathological forms of spermatozoa. Additionally, a dose-dependent effect on Leydig cells was observed. However, these PADE effects did not significantly affect male fertility nor fetal and offspring development when PADE-treated males were mated with intact females.ConclusionsPADE treatment of male rates negatively affected sperm and testicular Leydig cell morphology. However, these changes did not affect male fertility and offspring development. It is currently not known whether PADE treatment may affect human male fertility and offspring development. Therefore, these results from an animal study need to be confirmed in humans. Results from this animal study can be used to model the exposure-response relationship and adverse outcomes in humans.

Castration: Its economic implications on swineherd profitability

A 16-week trial was conducted to investigate the effect of castration on the profitability of the weaning to finishing operation of the swine enterprise. Eighteen pigs were allotted into three treatments comprising the male castrates (MC), the intact males (IM) and the intact females (IF), respectively. The pigs were exposed to the same management and environmental conditions throughout the duration of the trial. Total costs per treatment were N67,583.14, N68, 256.34 and 167,583.14 for the I.M, M.C and I.F and did not show any significant difference (P&gt;0.001). The gross margin per treatment however gave values (revenue) of N85,268±40.62 for the intact male group, N68,962±26.56 for the male castrate group and N69,588±35.38 for the I.F group with statistical significant differences (P&lt;0.001) between the I. M group and the other two groups. 97.08 cycles or 32.35 years were needed as the pay back period for the M.C. group. 33.67 cycles or 11.22 years for the I.F group and 3.82 cycles or 1.27 years for the I.M. group. The calculated return on capital employed (ROCE) gave values of 1.03 %, 26.17% and 2.97% for the M.C., I.M and I.F groups respectively. The study revealed an enormous economic damage that could be inflicted by castration as a management practice on the profitability of the weaning to finishing operation of the pig enterprise. The study also unlocked the huge economic benefit that could accrue to farmers when intact males as opposed to their male castrate counterparts are used in this line of pig production enterprise.

СТАТЕВА ПОВЕДІНКА НАЩАДКІВ САМИЦЬ ЩУРІВ НАРОДЖЕНИХ ВІД МАТЕРІВ РІЗНОГО ВІКУ З ФЕТОПЛАЦЕНТАРНОЮ НЕДОСТАТНІСТЮ

Sexual behaviour is an integral part of reproduction and is considered as a neuroendocrine function of the body. It is the result of sexual differentiation of the brain in the early stages of development of the body and is regulated by steroids of the gonads, which is confirmed by the presence of receptors for these hormones in the centre of sexual behaviour. Any negative factors during pregnancy can cause a lot of harm to the unborn child. To date, it is almost unknown how fetoplacental insufficiency affects the reproductive function of offspring of both sexes from birth to puberty very little. The purpose of this work was to study the effects of fetoplacental insufficiency of mothers of different ages on the sexual behaviour of female offspring. Materials and methods of research. The experiment involved healthy sexually mature female mothers of Wistar rats, young (3 months) and mature (10 months) of reproductive age, with a normal four to five day estrous cycle. 4 groups of 7 pregnant females were formed: 1 group, intact young animals; group 2, intact females of mature reproductive age; group 3, young females with experimental fetoplacental insufficiency; 4 - females with experimental fetoplacental insufficiency of mature reproductive age. Modelling of fetoplacental insufficiency was performed by daily subcutaneous injection to females from the 12th to the 18th day of pregnancy 50% oil solution of carbon tetrachloride at a dose of 2 ml/kg body weight. The sexual behaviour of females was studied according to generally accepted methods. After a study of sexual behaviour at the age of 3 months, female offspring were removed from the experiment. The uterus and ovaries were weighed, and the number of follicles in the ovary was counted. The estrous cycle of females was studied. Serum samples were taken to determine the concentration of the hormones estradiol and testosterone. Conclusions and prospects for further development. Fetoplacental insufficiency in young mothers of reproductive age affects the sexual behaviour of female offspring, reduces the number of lordosis reactions by almost 20% and increasing the receptive indicators of sexual behaviour. Such changes occur against the background of elevated levels of sex hormones while reducing the number of cycling females and the number of follicles in the ovary. Due to the fact that the rupture of the follicle and the release of the egg require sequential activation of the secretion of hypothalamic gonadotropin and luteinizing hormone, and against the background of fetoplacental insufficiency, there may be no preovulatory growth of their levels in the blood due to refractoriness of the ovaries. In the study of sexual behaviour of offspring of females born to mothers of mature reproductive age with fetoplacental insufficiency, a decrease in the number of lordosis reactions by 50% of the intact group and increased receptive behaviour were noted. Also, this group of offspring had a reduced number of cycling females but the number of follicles in the ovaries remained within the intact group. Such reproductive changes occurred against the background of elevated testosterone levels, without changes in estradiol concentrations, which led to the relative androgenization of females. The prospect of further development is to study the effects of fetoplacental insufficiency on the fertility of mature offspring of both sexes born to female rats of different reproductive ages with fetoplacental insufficiency. Key words: fetoplacental insufficiency, reproductive system, sexual behaviour, female offspring.