Factors affecting survival of adult female white-tailed deer after coyote establishment in south Carolina: Adult Female Deer Survival
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Biodiversity & Conservation↗
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DEHP exposure in utero disturbs sex determination and is potentially linked with precocious puberty in female mice
Human's ubiquitous exposure to di (2-ethylhexyl) phthalate (DEHP) is thought to be associated with female reproductive toxicity. Previous studies found that DEHP inhibited follicle growth and decreased estradiol levels in adult female mice. However, limited information is available on the link between in utero DEHP exposure and ovarian development in female mouse offspring. The present study evaluates the disturbances in regulatory genes involved in female sex determination and the ovarian outcomes in fetal and postnatal female mice treated with in utero DEHP exposure. Pregnant mice were exposed to DEHP by gavage, with the dosage regime beginning at human relevant exposure levels. After in utero DEHP exposure, increased follicular atresia was observed in the female pups at postnatal days (PND) 21. Foxl2 expression was significantly upregulated, and Fst was significantly downregulated by DEHP above 2 mg/kg/d at PND 1 and 21. This suggests that lesion of granulosa cell differentiation and disturbance of follicle development in postnatal female mice. The expression of Cyp11a1 and Star were significantly downregulated by in utero DEHP exposure, indicating effects on estradiol biosynthesis. The female sex determination pathway was disturbed in fetus by DEHP at 2 mg/kg/d and above during the critical time window of sex determination causing significant upregulation of Foxl2, Wnt4, β-catenin and Fst. Furthermore, the increased expression of Wnt4 was supported by whole-mount in situ hybridization (WISH). These results suggest a possible association between in utero DEHP exposure and precocious puberty in the postnatal life of mice offspring, where disturbance of the sex determination regulating pathway acted as an important mechanism. - Highlights: • Maternal exposure to di (2-ethylhexyl) phthalate disturbs fetus sex determination. • DEHP upregulated Foxl2 expression potentially disturbs postnatal granulosa cell differentiation. • DEHP accelerated medulla follicular atresia potentially leading to precocious puberty.
60 APPLIED LIFE SCIENCES↗
β-cell serotonin production is associated with female sex, old age, and diabetes-free condition
Serotonin is known to be present in pancreatic β-cells and to play several physiological roles, including insulin secretion, β-cell proliferation, and paracrine inhibition of α-cells. However, the serotonin production of different cell lines and islets has not been compared based on age, sex, and diabetes related conditions. Here, we directly compared the serotonin concentrations in βTC and MIN6 cell lines, as well as in islets from mice using ultra-performance liquid chromatography tandem mass spectrometry. The average serotonin concentration was 5–10 ng/mg protein in the islets of male and non-pregnant female mice. The serotonin level was higher in females than males at 8 weeks, although there was no difference at 1 year. Furthermore, we observed serotonin by immunofluorescence staining in the pancreatic tissues of mice and human. Serotonin was detected by immunofluorescence staining in a portion of β-cells from islets of old female mice, but not of male or young female mice. A similar pattern was observed in human pancreas as well. In humans, serotonin production in β-cells was associated with a diabetes-free condition. Thus, serotonin production in β-cells was associated with old age, female sex, and diabetes-free condition. - Highlights: • Actual serotonin concentrations in cell lines and islets are compared. • Serotonin over-production in mouse β-cell is aged and female specific. • Ovariectomy lowers serotonin concentrations in islets. • Serotonin over-production in human β-cell is aged, female, and non-diabetes specific.
60 APPLIED LIFE SCIENCES↗
Maternal exposure to di(2-ethylhexyl)phthalate (DEHP) promotes the transgenerational inheritance of adult-onset reproductive dysfunctions through the female germline in mice
Endocrine disruptors (EDs) are compounds known to promote transgenerational inheritance of adult-onset disease in subsequent generations after maternal exposure during fetal gonadal development. This study was designed to establish whether gestational and lactational exposure to the plasticizer di(2-ethylhexyl)phthalate (DEHP) at environmental doses promotes transgenerational effects on reproductive health in female offspring, as adults, over three generations in the mouse. Gestating F0 mouse dams were exposed to 0, 0.05, 5 mg/kg/day DEHP in the diet from gestational day 0.5 until the end of lactation. The incidence of adult-onset disease in reproductive function was recorded in F1, F2 and F3 female offspring. In adult F1 females, DEHP exposure induced reproductive adverse effects with: i) altered ovarian follicular dynamics with reduced primordial follicular reserve and a larger growing pre-antral follicle population, suggesting accelerated follicular recruitment; ii) reduced oocyte quality and embryonic developmental competence; iii) dysregulation of the expression profile of a panel of selected ovarian and pre-implantation embryonic genes. F2 and F3 female offspring displayed the same altered reproductive morphological phenotype and gene expression profiles as F1, thus showing transgenerational transmission of reproductive adverse effects along the female lineage. These findings indicate that in mice exposure to DEHP at doses relevant to human exposure during gonadal sex determination significantly perturbs the reproductive indices of female adult offspring and subsequent generations. Evidence of transgenerational transmission has important implications for the reproductive health and fertility of animals and humans, significantly increasing the potential biohazards of this toxicant. - Highlights: • Maternal exposure to DEHP transgenerationally affects female reproductive health. • DEHP reduced ovarian follicular reserve up to the third generation. • DEHP reduced oocyte and blastocyst developmental competence up to F3. • DEHP altered expression levels for key genes in ovary and blastocysts up to F4. • DEHP's adverse effects were observed at doses relevant for human exposure.
60 APPLIED LIFE SCIENCES↗
Male breast cancer incidence and mortality risk in the Japanese atomic bomb survivors – Differences in excess relative and absolute risk from female breast cancer
There are well-known associations of ionizing radiation with female breast cancer, and emerging evidence also for male breast cancer. In the UK, female breast cancer following occupational radiation exposure is among that set of cancers eligible for state compensation and consideration is currently being given to an extension to include male breast cancer. The objectives here, compare radiation-associated excess relative and absolute risks of male and female breast cancers. Breast cancer incidence and mortality data in the Japanese atomic-bomb survivors were analyzed using relative and absolute risk models via Poisson regression. As a result, we observed significant ( p≤ 0.01) dose-related excess risk for male breast cancer incidence and mortality. For incidence and mortality data, there are approximate 15-fold and 5- fold elevations, respectively, of relative risk for male compared with female breast cancer incidence, the former borderline significant (p = 0.050). In contrast, for incidence and mortality data there are approximate 20-fold and 10-fold elevations, respectively, of female absolute risk compared with male, both statistically significant (p < 0.001). There are no indications of differences between the sexes in age/time-since-exposure/age-at-exposure modifications to the relative or absolute excess risk. The probability of causation of male breast cancer following radiation exposure exceeds by at least 5-fold that of many other malignancies. In conclusion, there is evidence of much higher radiation-associated relative risk for male than for female breast cancer, although absolute excess risks for males are much less than for females. However, the small number of male cases and deaths suggests a degree of caution in interpretation of this finding.
60 APPLIED LIFE SCIENCES↗
DIFFERENTIAL CANID PREDATION OF TRANSLOCATED JUVENILE DESERT TORTOISES AND CHEMICAL SIGNATURE DIFFERENCES BETWEEN FEMALE AND MALE ADULT AND JUVENILE DESERT TORTOISES
Differential predation was observed in a population of 59 translocated juvenile Desert Tortoises (Gopherus agassizii) of known sex during a juvenile translocation survival study between September 2012 and November 2017. The main source of mortality (77%; 24 of 31 deaths) was attributed to Coyote (Canis latrans) and Kit Fox (Vulpes macrotis) predation. Predation was skewed with 71% (n = 17) female mortality versus 29% (n = 7) male mortality. We tested the hypothesis that juvenile females smell different than males which leads to increased canid predation. We also explored differences in chemical signatures of resident adult female and male Desert Tortoises. We collected oral, cloacal and chin/forelimb swabs from translocated juvenile and resident adult female and male tortoises during fall 2015 and fall 2017 and analyzed them using headspace gas chromatography/mass spectrometry to determine potential differences in the chemical signatures among the four groups. Standardized chromatographic peak responses were subjected to repeated analyses of variance (ANOVA). For development of artificial scents, mean responses were calculated for each juvenile tortoise from standardized responses representing all collections (i.e., oral, cloacal, and chin/forelimb swabs) and grand means were determined for males and females. Repeated measures ANOVAs clearly demonstrated that the collections of volatiles differed according to age and/or sex depending on the body location of collection. Among the plausibly endogenous volatiles that differed by age, many of them are alcohols. Two field trials using captive Coyotes and one field trial partially within the translocation area were conducted to test if Coyotes showed a preference for female or bias against male synthesized scent. No consistent preference or bias was shown, suggesting that no innate preference for female odor was evident.
60 APPLIED LIFE SCIENCES↗
Integrative epigenomic analysis reveals unique epigenetic signatures involved in unipotency of mouse female germline stem cells
Background: Germline stem cells play an essential role in establishing the fertility of an organism. Although extensively characterized, the regulatory mechanisms that govern the fundamental properties of mammalian female germline stem cells remain poorly understood. Results: We generate genome-wide profiles of the histone modifications H3K4me1, H3K27ac, H3K4me3, and H3K27me3, DNA methylation, and RNA polymerase II occupancy and perform transcriptome analysis in mouse female germline stem cells. Comparison of enhancer regions between embryonic stem cells and female germline stem cells identifies the lineage-specific enhancers involved in germline stem cell features. Additionally, our results indicate that DNA methylation primarily contributes to female germline stem cell unipotency by suppressing the somatic program and is potentially involved in maintenance of sexual identity when compared with male germline stem cells. Moreover, we demonstrate down-regulation of Prmt5 triggers differentiation and thus uncover a role for Prmt5 in maintaining the undifferentiated status of female germline stem cells. Conclusions: The genome-wide epigenetic signatures and the transcription regulators identified here provide an invaluable resource for understanding the fundamental features of mouse female germline stem cells.
59 BASIC BIOLOGICAL SCIENCES↗
Low cadmium exposure in males and lactating females–estimation of biomarkers
Background: Urine cadmium (Cd) and renal function biomarkers, mostly analysed in urine spot samples, are well established biomarkers of occupational exposure. Their use and associations at low environmental level are common, but have recently been questioned, particularly in terms of physiological variability and normalisation bias in the case of urine spot samples. Aim: To determine the appropriateness of spot urine and/or blood Cd exposure biomarkers and their relationships with renal function biomarkers at low levels of exposure. To this end, we used data from Slovenian human biomonitoring program involving 1081 Slovenians (548 males, mean age 31 years; 533 lactating females, mean age 29 years; 2007–2015) who have not been exposed to Cd occupationally. Results: Geometric means (GMs) of Cd in blood and spot urine samples were 0.27 ng/mL (0.28 for males and 0.33 for females) and 0.19 ng/mL (0.21 for males and 0.17 for females), respectively. Differing results were obtained when contrasting normalisation by urine creatinine with specific gravity. GMs of urine albumin (Alb), alpha-1-microglobulin (A1M), N-acetyl-beta-glucosaminidase (NAG), and immunoglobulin G (IgG) were far below their upper reference limits. Statistical analysis of unnormalised or normalised urine data often yielded inconsistent and conflicting results (or trends), so association analyses with unnormalised data were taken as more valid. Relatively weak positive associations were observed between urine Cd (ng/mL) and blood Cd (β=0.11, p=0.002 for males and β=0.33, p<0.001 for females) and for females between urine NAG and blood Cd (β=0.14, p=0.04). No associations were found between other renal function biomarkers and blood Cd. Associations between Cd and renal function biomarkers in urine were stronger (p<0.05, β=0.11–0.63). Mostly, all of the associations stayed significant but weakened after normalisation for diuresis. In the case of A1M, its associations with Cd were influenced by current smoking and blood Pb in males and by pre-pregnancy smoking and blood Se in females (β up to 0.34, p<0.001). Statistical analysis of unnormalised or normalised urine data often yielded inconsistent and conflicting results (or trends), so association analyses data with unnormalised were taken as more valid. Conclusions: The observed uncertainties introduced by urine normalisation, particularly by creatinine, confirm blood Cd as a superior low-Cd exposure biomarker versus urine Cd in cases when 24 h urine is unattainable. Evidence that A1M can be positively related to Cd, smoking (current or pre-pregnancy), Pb, and Se status, points to the versatile biological functions of A1M. - Highlights: • Creatinine normalisation of spot urine data is inappropriate at low Cd exposure. • Blood Cd as low-Cd exposure biomarker is superior over spot urine Cd. • Cd in urine, but not in blood, was significantly associated with A1M. • A1M – Cd relations were influenced by smoking, Se and less so by Pb.
60 APPLIED LIFE SCIENCES↗
Pregnancy level of estradiol attenuated virus-specific humoral immune response in H5N1-infected female mice despite inducing anti-inflammatory protection
Estradiol, a major female steroid produced during pregnancy, has been reported to protect ovariectomized animals against H1N1 influenza infections via its anti-inflammatory effects. However, it remains unclear why pregnant women with high gestational estradiol levels are highly susceptible to influenza infections. This study was aimed to investigate the effects of pregnancy level of estradiol on female immunity against H5N1 infection in Balb/c mice. A sex-dependent susceptibility to H5N1 infection (higher morbidity and higher mortality) was observed in both pregnant and non-pregnant female mice as compared to male mice. Subcutaneous implantation of estradiol pellets increased serum estradiol concentrations of non-pregnant female mice to the pregnancy level. These mice were protected from H5N1 infection through downregulation of pulmonary pro-inflammatory cytokines. However, the production of virus-specific antibodies after infection was significantly delayed in estradiol-implanted mice when compared to placebos. Virus-specific IgG-secreting and IL-4-secreting cells were also reduced in estradiol-implanted mice. Similarly, lower antibody titers to seasonal vaccine antigens were found in pregnant women as compared to non-pregnant females without hormone usage. Our results indicate that estradiol levels equivalent to those found during pregnancy have divergent effects on female immunity against influenza, highlighting the importance of vaccination during pregnancy to prevent severe influenza infections.
60 APPLIED LIFE SCIENCES↗
Bisphenol A, bisphenol F and bisphenol S affect differently 5α-reductase expression and dopamine–serotonin systems in the prefrontal cortex of juvenile female rats
Background: Early-life exposure to the endocrine disruptor bisphenol A (BPA) affects brain function and behavior, which might be attributed to its interference with hormonal steroid signaling and/or neurotransmitter systems. Alternatively, the use of structural analogs of BPA, mainly bisphenol F (BPF) and bisphenol S (BPS), has increased recently. However, limited in vivo toxicity data exist. Objectives: We investigated the effects of BPA, BPF and BPS on 5α-reductase (5α-R), a key enzyme involved in neurosteroidogenesis, as well as on dopamine (DA)- and serotonin (5-HT)-related genes, in the prefrontal cortex (PFC) of juvenile female rats. Methods: Gestating Wistar rats were treated with either vehicle or 10 μg/kg/day of BPA, BPF or BPS from gestational day 12 to parturition. Then, female pups were exposed from postnatal day 1 through day 21 (PND21), when they were euthanized and RT-PCR, western blot and quantitative PCR-array experiments were performed. Results: BPA decreased 5α-R2 and 5α-R3 mRNA and protein levels, while both BPF and BPS decreased 5α-R3 mRNA levels in PFC at PND21. Further, BPA, BPF and BPS significantly altered, respectively, the transcription of 25, 56 and 24 genes out of the 84 DA and 5-HT-related genes assayed. Of particular interest was the strong induction by all these bisphenols of Cyp2d4, implicated in corticosteroids synthesis. Conclusions: Our results demonstrate for the first time that BPA, BPF and BPS differentially affect 5α-R and genes related to DA/5-HT systems in the female PFC. In vivo evidence of the potential adverse effects of BPF and BPS in the brain of mammals is provided in this work, raising questions about the safety of these chemicals as substitutes for BPA. - Highlights: • Juvenile prefrontal cortex of female rats exposed to bisphenol A, F or S was analyzed. • We provide the first in vivo data of BPF and BPS effects in mammal brain. • BPA, BPF and BPS differently affected dopamine and serotonin-related genes. • 5α-reductase was found as a potential target for BPA action in juvenile female brain.
60 APPLIED LIFE SCIENCES↗
Female Representation in the Academic Oncology Physician Workforce: Radiation Oncology Losing Ground to Hematology Oncology
Purpose: Our purpose was to assess comparative female representation trends for trainees and full-time faculty in the academic radiation oncology and hematology oncology workforce of the United States over 3 decades. Methods and Materials: Simple linear regression models with year as the independent variable were used to determine changes in female percentage representation per year and associated 95% confidence intervals for trainees and full-time faculty in each specialty. Results: Peak representation was 48.4% (801/1654) in 2013 for hematology oncology trainees, 39.0% (585/1499) in 2014 for hematology oncology full-time faculty, 34.8% (202/581) in 2007 for radiation oncology trainees, and 27.7% (439/1584) in 2015 for radiation oncology full-time faculty. Representation significantly increased for trainees and full-time faculty in both specialties at approximately 1% per year for hematology oncology trainees and full-time faculty and 0.3% per year for radiation oncology trainees and full-time faculty. Compared with radiation oncology, the rates were 3.84 and 2.94 times greater for hematology oncology trainees and full-time faculty, respectively. Conclusion: Despite increased female trainee and full-time faculty representation over time in the academic oncology physician workforce, radiation oncology is lagging behind hematology oncology, with trainees declining in recent years in radiation oncology; this suggests a de facto ceiling in female representation. Whether such issues as delayed or insufficient exposure, inadequate mentorship, or specialty competitiveness disparately affect female representation in radiation oncology compared to hematology oncology are underexplored and require continued investigation to ensure that the future oncologic physician workforce reflects the diversity of the population it serves.
62 RADIOLOGY AND NUCLEAR MEDICINE↗
Omics Analyses of Trichoderma reesei CBS999.97 and QM6a Indicate the Relevance of Female Fertility to Carbohydrate-Active Enzyme and Transporter Levels
Here, the filamentous fungus Trichoderma reesei is found predominantly in the tropics but also in more temperate regions, such as Europe, and is widely known as a producer of large amounts of plant cell wall-degrading enzymes. We sequenced the genome of the sexually competent isolate CBS999.97, which is phenotypically different from the female sterile strain QM6a but can cross sexually with QM6a. Transcriptome data for growth on cellulose showed that entire carbohydrate-active enzyme (CAZyme) families are consistently differentially regulated between these strains. We evaluated backcrossed strains of both mating types, which acquired female fertility from CBS999.97 but maintained a mostly QM6a genetic background, and we could thereby distinguish between the effects of strain background and female fertility or mating type. We found clear regulatory differences associated with female fertility and female sterility, including regulation of CAZyme and transporter genes. Analysis of carbon source utilization, transcriptomes, and secondary metabolites in these strains revealed that only a few changes in gene regulation are consistently correlated with different mating types. Different strain backgrounds (QM6a versus CBS999.97) resulted in the most significant alterations in the transcriptomes and in carbon source utilization, with decreased growth of CBS999.97 on several amino acids (for example proline or alanine), which further correlated with the downregulation of genes involved in the respective pathways. In combination, our findings support a role of fertility-associated processes in physiology and gene regulation and are of high relevance for the use of sexual crossing in combining the characteristics of two compatible strains or quantitative trait locus (QTL) analysis.
59 BASIC BIOLOGICAL SCIENCES↗
Importance of Depth and Artificial Structure as Predictors of Female Red Snapper Reproductive Parameters
Abstract The Red Snapper Lutjanus campechanus is a structure‐associated species occurring across a wide depth range in the northern Gulf of Mexico. We used the random forest machine learning algorithm to understand which habitat and individual fish characteristics could predict reproductive parameters of female Red Snapper. We evaluated fish captured from 2016 to 2018 on three artificial structure types with various structure heights at depths of 100 m or less. Overall, we found that depth and month were important predictors for most reproductive parameters, but the type of structure (artificial reefs, oil platforms, and rigs‐to‐reefs structures) was not important. Maturity was correctly classified in 88.9% of the cases when using the random forest ensemble model, with important predictors including FL, depth, structure height, and month of collection. Spawning seasonality (measured as gonadosomatic index [GSI]) was correctly classified in 59.5% of the cases when using histology reproductive phase, FL, month, and depth variables. Reproductively active or inactive females were correctly classified in 89.3% of the cases using GSI, month, FL, and depth, while females in the developing versus spawning capable phases were correctly classified in 82.2% of the cases using GSI, FL, month, and depth. Histological indicators that show potential spawning within a 36‐h period were correctly classified 61.5% of the time, with the best predictors being depth, FL, GSI, and month. Stepwise regression indicated that month was the only factor that significantly predicted contrasts in relative batch fecundity, with significantly greater values in August compared to all other months. Our findings suggest that female Red Snapper reproductive effort is not consistently or well predicted by artificial structure type or height but that a combination of fish FL, month, and depth can predict reproductive characteristics of female Red Snapper.
Brown‐Peterson, Nancy J.↗
Multiple Paternity Benefits Female Marbled Salamanders by Increasing Survival of Progeny to Metamorphosis
Abstract Multiple paternity occurs in most species and animal groups that have been studied. Because mating involves fitness costs to individual females, theory predicts that polyandrous females gain greater fitness benefits than costs, allowing the behavior to be maintained. Genetic, rather than material, benefits often occur in species where males provide females with little more than sperm and seminal fluid. We compared fitness correlates of single‐ and double‐sire clutches from female marbled salamanders ( Ambystoma opacum ) at the egg, hatchling, and metamorph stages of offspring development. Because clutches were collected from experimental breeding groups, strict paternity exclusion of offspring using microsatellite data allowed us to categorize each clutch as having either one or two fathers. Early offspring viability and size of hatchlings were not different between single‐ and multiple‐paternity clutches. Larvae from the two clutch types were allowed to develop together in field enclosures until metamorphosis. Although there was no difference in size at metamorphosis, survival to metamorphosis was significantly higher in multiple‐paternity clutches (44% vs. 40%) suggesting a benefit for females. The results were consistent with genetic benefits, although maternal effects could not be ruled out. The data did not support predictions of the genetic bet‐hedging and good sperm hypotheses for genetic benefits of polyandry.
Croshaw, Dean A.↗
Effects of Six Sequential Charged Particle Beams on Behavioral and Cognitive Performance in B6D2F1 Female and Male Mice
The radiation environment astronauts are exposed to in deep space includes galactic cosmic radiation (GCR) with different proportions of all naturally occurring ions. To assist NASA with assessment of risk to the brain following exposure to a mixture of ions broadly representative of the GCR, we assessed the behavioral and cognitive performance of female and male C57BL/6J × DBA2/J F1 (B6D2F1) mice two months following rapidly delivered, sequential 6 beam irradiation with protons (1 GeV, LET = 0.24 keV, 50%), 4 He ions (250 MeV/n, LET = 1.6 keV/μm, 20%), 16 O ions (250 MeV/n, LET = 25 keV/μm 7.5%), 28 Si ions (263 MeV/n, LET = 78 keV/μm, 7.5%), 48Ti ions (1 GeV/n, LET = 107 keV/μm, 7.5%), and 56 Fe ions (1 GeV/n, LET = 151 keV/μm, 7.5%) at 0, 25, 50, or 200 cGy) at 4–6 months of age. When the activity over 3 days of open field habituation was analyzed in female mice, those irradiated with 50 cGy moved less and spent less time in the center than sham-irradiated mice. Sham-irradiated female mice and those irradiated with 25 cGy showed object recognition. However, female mice exposed to 50 or 200 cGy did not show object recognition. When fear memory was assessed in passive avoidance tests, sham-irradiated mice and mice irradiated with 25 cGy showed memory retention while mice exposed to 50 or 200 cGy did not. The effects of radiation passive avoidance memory retention were not sex-dependent. There was no effect of radiation on depressive-like behavior in the forced swim test. There was a trend toward an effect of radiation on BDNF levels in the cortex of males, but not for females, with higher levels in male mice irradiated with 50 cGy than sham-irradiated. Finally, sequential 6-ion irradiation impacted the composition of the gut microbiome in a sex-dependent fashion. Taxa were uncovered whose relative abundance in the gut was associated with the radiation dose received. Thus, exposure to sequential six-beam irradiation significantly affects behavioral and cognitive performance and the gut microbiome.
60 APPLIED LIFE SCIENCES↗
{sup 18}F-FDG-PET in Finnish patients with clinical suspicion of cardiac sarcoidosis: Female sex and history of atrioventricular block increase the prevalence of positive PET findings
Introduction: Fluorodeoxyglucose positron emission tomography (FDG-PET) is a non-invasive imaging modality that has been shown to be a feasible method to demonstrate myocardial inflammation. The aim of this study was to identify the patients suspected of having cardiac sarcoidosis (CS), who are most likely to benefit from PET imaging. Materials and methods: 137 patients suspected of having CS underwent a dedicated cardiac FDG-PET examination at Tampere University Hospital between August 2012 and September 2015. These examinations were retrospectively analyzed. Results: 33 and 12 of the 137 patients had abnormal left and right ventricular (LV and RV) FDG-uptake, respectively. Abnormal LV-uptake and RV-uptake were significantly associated with female sex and a history of advanced AV-block (P < 0.05). Abnormal RV-uptake was also associated with ventricular tachycardia and atrial fibrillation (P < 0.05). 56% of the 27 female patients with a history of AV-block had a pathological PET finding compared to only 6% of the 49 male patients without a history of AV-block. There were 17 female patients with history of both AV-block and ventricular tachycardia, 71% of them had abnormal PET finding. Conclusions: Abnormal FDG-PET findings were associated with female sex, AV-block, and arrhythmias in this clinical cohort.
62 RADIOLOGY AND NUCLEAR MEDICINE↗
Prenatal exposure to an environmentally relevant phthalate mixture disrupts reproduction in F1 female mice
Phthalates are used in a large variety of products, such as building materials, medical devices, and personal care products. Most previous studies on the toxicity of phthalates have focused on single phthalates, but it is also important to study the effects of phthalate mixtures because humans are exposed to phthalate mixtures. Thus, we tested the hypothesis that prenatal exposure to an environmentally relevant phthalate mixture adversely affects female reproduction in mice. To test this hypothesis, pregnant CD-1 dams were orally dosed with vehicle (tocopherol-stripped corn oil) or a phthalate mixture (20 and 200 μg/kg/day, 200 and 500 mg/kg/day) daily from gestational day 10 to birth. The mixture was based on the composition of phthalates detected in urine samples from pregnant women in Illinois. The mixture included 35% diethyl phthalate, 21% di(2-ethylhexyl) phthalate, 15% dibutyl phthalate, 15% diisononyl phthalate, 8% diisobutyl phthalate, and 5% benzylbutyl phthalate. Female mice born to the exposed dams were subjected to tissue collections and fertility tests at different ages. Our results indicate that prenatal exposure to the phthalate mixture significantly increased uterine weight and decreased anogenital distance on postnatal days 8 and 60, induced cystic ovaries at 13 months, disrupted estrous cyclicity, reduced fertility-related indices, and caused some breeding complications at 3, 6, and 9 months of age. Collectively, our data suggest that prenatal exposure to an environmentally relevant phthalate mixture disrupts aspects of female reproduction in mice. - Highlights: • Prenatal exposure to a phthalate mixture disrupts F1 estrous cyclicity. • Prenatal exposure to a phthalate mixture induces F1 ovarian cysts. • Prenatal exposure to a phthalate mixture decreases F1 female fertility-related indices. • Prenatal exposure to a phthalate mixture induces F1 breeding complications.
60 APPLIED LIFE SCIENCES↗
Environmental obesogen tributyltin chloride leads to abnormal hypothalamic-pituitary-gonadal axis function by disruption in kisspeptin/leptin signaling in female rats
Tributyltin chloride (TBT) is a xenobiotic used as a biocide in antifouling paints that has been demonstrated to induce endocrine-disrupting effects, such as obesity and reproductive abnormalities. An integrative metabolic control in the hypothalamus-pituitary-gonadal (HPG) axis was exerted by leptin. However, studies that have investigated the obesogenic TBT effects on the HPG axis are especially rare. We investigated whether metabolic disorders as a result of TBT are correlated with abnormal hypothalamus-pituitary-gonadal (HPG) axis function, as well as kisspeptin (Kiss) action. Female Wistar rats were administered vehicle and TBT (100 ng/kg/day) for 15 days via gavage. We analyzed their effects on the tin serum and ovary accumulation (as biomarker of TBT exposure), estrous cyclicity, surge LH levels, GnRH expression, Kiss action, fertility, testosterone levels, ovarian apoptosis, uterine inflammation, fibrosis, estrogen negative feedback, body weight gain, insulin, leptin, adiponectin levels, as well as the glucose tolerance (GTT) and insulin sensitivity tests (IST). TBT led to increased serum and ovary tin levels, irregular estrous cyclicity, and decreased surge LH levels, GnRH expression and Kiss responsiveness. A strong negative correlation between the serum and ovary tin levels with lower Kiss responsiveness and GnRH mRNA expression was observed in TBT rats. An increase in the testosterone levels, ovarian and uterine fibrosis, ovarian apoptosis, and uterine inflammation and a decrease in fertility and estrogen negative feedback were demonstrated in the TBT rats. We also identified an increase in the body weight gain and abnormal GTT and IST tests, which were associated with hyperinsulinemia, hyperleptinemia and hypoadiponectinemia, in the TBT rats. TBT disrupted proper functioning of the HPG axis as a result of abnormal Kiss action. The metabolic dysfunctions co-occur with the HPG axis abnormalities. Hyperleptinemia as a result of obesity induced by TBT may be associated with abnormal HPG function. A strong negative correlation between the hyperleptinemia and lower Kiss responsiveness was observed in the TBT rats. These findings provide evidence that TBT leads to toxic effects direct on the HPG axis and/or indirectly by abnormal metabolic regulation of the HPG axis. - Highlights: • TBT disrupted proper functioning of the HPG axis in female rats. • TBT leads to obesity and abnormal kisspeptin/leptin signaling in female rats. • TBT impairs GnRH neurons function, estrogen negative feedback role and fertility in female rats. • TBT leads to hyperleptinemia that may be associated at least in part with abnormal HPG function.
60 APPLIED LIFE SCIENCES↗