Interleukin-10 deficiency induces thoracic perivascular adipose tissue whitening and vascular remodeling.

Perivascular adipose tissue (PVAT) is an adipose layer, surrounding blood vessels, with a local modulatory role. Interleukin-10 (IL-10) has been shown to modulate vascular tissue. This study aimed to characterize the endogenous role of IL-10 in vascular remodeling, and PVAT phenotyping. Thoracic aortic segments from control (C57BL/6J) and IL-10 knockout (IL-10-/-) male mice were used. Analyzes of aorta/PVAT morphometry, and elastin, collagen and reticulin deposition were performed. Tissue uncoupling protein 1 (UCP1) was accessed by Western blotting. Endogenous absence of IL-10 reduced total PVAT area (p = 0.0310), and wall/lumen ratio (p = 0.0024), whereas increased vascular area and thickness (p < 0.0001). Total collagen deposition was augmented in IL-10-/-, but under polarized light, the reduction of collagen-I (p = 0.0075) and the increase of collagen-III (p = 0.0055) was found, simultaneously with reduced elastic fibers deposition (p = 0.0282) and increased deposition of reticular fibers (p < 0.0001). Adipocyte area was augmented in the IL-10 absence (p = 0.0225), and UCP1 expression was reduced (p = 0.0420). Moreover, relative frequency of white adipose cells and connective tissue was augmented in IL-10-/- (p < 0.0001), added to a reduction in brown adipose cells (p < 0.0001). Altogether, these data characterize aorta PVAT from IL-10-/- as a white-like adipocyte phenotype. Endogenous IL-10 prevents vascular remodeling and favors a brown-like adipocyte phenotype, suggesting a modulatory role for IL-10 in PVAT plasticity.

Neurodevelopmental signature of a transcriptome-based polygenic risk score for depression.

Disentangling the molecular underpinnings of major depressive disorder (MDD) is necessary for identifying new treatment and prevention targets. The functional impact of depression-related transcriptomic changes on the brain remains relatively unexplored. We recently developed a novel transcriptome-based polygenic risk score (tPRS) composed of genes transcriptionally altered in MDD. Here, we sought to investigate effects of tPRS on brain structure in a developmental cohort (Adolescent Brain Cognitive Development study; n = 5124; 2387 female) at baseline (9-10 years) and 2-year follow-up (11-12 years). We tested associations between tPRS and Freesurfer-derived measures of cortical thickness, cortical surface area, and subcortical volume. Across the whole sample, higher tPRS was significantly associated with thicker left posterior cingulate cortex at both baseline and 2-year follow-up. In females only, tPRS was associated with lower right hippocampal volume at baseline and 2-year follow-up, and lower right pallidal volume at baseline. Furthermore, regional subcortical volume significantly mediated an indirect effect of tPRS on depressive symptoms in females at both timepoints. Conversely, tPRS did not have significant effects on cortical surface area. These findings suggest the existence of a sex-specific neurodevelopmental signature associated with shifts towards a more depression-like brain transcriptome, and highlight novel pathways of developmentally mediated MDD risk.

Pharmacological Characteristics of the Hydroethanolic Extract of Acmella oleracea (L) R. K. Jansen Flowers: ADME/Tox In Silico and In Vivo Antihypertensive and Chronic Toxicity Evaluation.

Acmella oleracea (L.) R. K. Jansen, popularly known as jambu in Northern Brazil, is widely used in folk medicine and local cuisine. Its consumption in different ways reinforces the need for safety assessments. In this study, the major compounds found in the hydroethanolic extract of A. oleracea flowers (EHFAO) were characterized by ultra-performance liquid mass spectrometry (UHPLC-ESI-QTOF-MS/MS). The effects of oral administration of 100/mg/kg of EHFAO extract over 60 days in male spontaneously hypertensive (SHR) and Wistar (WR) rats and the in silico ADME/Tox predictions, lipophilicity, and water solubility were accomplished for the compounds identified. Spilanthol was detected as the foremost major compound at a concentration of 97.7%, followed by 1.53% scopoletin and 0.77% d-limonene. The treatment with EHFAO did not alter the animals´ weight over the studied period. Moderate alterations were observed solely in the hepatic enzymes AST (WR = 97 UI/L and SHR = 150 UI/L ∗ p < 0.05) and ALT (WR = 55 UI/L and SHR = 95 UI/L ∗ p < 0.05), while no relevant histopathological alterations were found. The in-silico study confirmed the in vivo findings, as the identified compounds were considered highly bioactive orally, due to their drug similarity profiles, adequate lipid solubility, bioavailability, and pharmacokinetics. Therefore, the chronic treatment with EHFAO was found safe at the concentration of 100/mg/kg, with no interference in the blood pressure levels neither appreciable toxic effects.

Theranostics for COVID-19 Antiviral Drugs: Prospects and Challenges for Worldwide Precision/Personalized Medicine.

Coronavirus disease 2019 (COVID-19) is a systemic disease that impacts multiple organ systems with a complex clinical presentation and outcomes that can vary from person to person and between populations. To optimize COVID-19 treatment outcomes, and in light of the availability of antiviral drugs, there is a need for greater attention to the field of theranostics, the fusion of therapeutics and diagnostics. Theranostics tests would be invaluable, we suggest in this expert review, so as to optimize the efficacy and safety of current and future antiviral drugs against COVID-19. Theranostics would also assist in the design and implementation of clinical trials with antiviral drug candidates. We discuss here theranostics considering drugs such as remdesivir, Paxlovid™, and molnupiravir. All in all, we underscore that theranostics as a concept and practice is essential for efficient and safe health interventions against COVID-19 and other ecological crises in the 21st century.

Female Prostate Development: Morphological Analysis of the Budding Dynamic.

The presence of the prostate in female mammals has long been known. However, pieces of information related to its development are still lacking. The aim of this study was to explore the budding dynamic during the initial prostate development in female gerbils. Pregnant females were timed, the fetuses were euthanized, and the urogenital sinus was dissected out between the embryonic days 20 and 24 (E20-E24 groups). Newborn pups (1-day-old; P1 group) underwent the same procedures. The female prostate development was based on epithelial buds which arose far from the paraurethral mesenchyme (PAM). The epithelial buds reached the PAM at prenatal day 24, crossing a small gap in the smooth muscle layer between the periurethral mesenchyme (PEM) and the PAM. Steroid nuclear receptors such as the androgen receptor and estrogen receptor alpha were localized in the PEM through the urethral wall, although some epithelial labeling was also present in the urogenital sinus epithelium (UGE). P63-positive cells were found only in the UGE, becoming restricted to the basal compartment after the 23rd prenatal day. The results showed that the gerbil female prostate exhibits a distinct budding pattern as compared to the male prostate development.

Decreasing sperm quality in mice subjected to chronic cannabidiol exposure: New insights of cannabidiol-mediated male reproductive toxicity.

Cannabidiol (CBD) is a natural cannabinoid present in the Cannabis sativa plant, widely prescribed as an anticonvulsant drug, especially for pediatric use. However, its effects on male reproduction are still little investigated. Therefore, the present study assessed the effects of CBD on the spermatogenesis and sperm quality. For this, twenty-one-day-old Swiss mice received CBD for 34 consecutive days by gavage at doses of either 15 or 30 mg/kg. Chronic exposure to CBD decreased the frequency of stages VII-VIII and XII of spermatogenesis and an increase in the frequency of stage IX were noted. Furthermore, the seminiferous epithelium height reduced at stage IX and increased at stage XII in both CBD-treated groups. There was a significant rise of sperm DNA damage, while no genotoxic effects were observed in leukocytes. The activities of superoxide dismutase and catalase decreased, while malondialdehyde levels increased in the sperm of mice treated with a higher dose of CBD. Mice exposed to 30 mg/kg of CBD showed a reduction in the mobile spermatozoa percentage and in curvilinear velocity, while straight line and average path velocity decreased in both treated groups. The number of acrosome-intact spermatozoa declined in the CBD 30 group, and the number of abnormal acrosomes raised in both CBD groups. On the other hand, the weight of reproductive organs, sperm count, and hormone levels were not affected by CBD treatment. These findings show that dysregulation of the endocannabinoid system by CBD can reduce sperm quality. The mechanisms responsible may be associated with disorders during spermatogenesis, especially during the final stages of nuclear remodelling and assembly of acrosome. However, changes in mitochondrial function, as well as the reduction on the antioxidant enzyme activities during epididymal transit, at least partly, may also be involved.

In vivo effect of orally given polyvinyl alcohol/starch nanocomposites containing bioactive peptides from Phaseolus vulgaris beans.

In this study, a nanocomposite produced with a blend of polyvinyl alcohol and partially hydrolyzed starch from Solanum lycocarpum was used as a matrix to entrap natural bioactive peptides from Phaseolus vulgaris. The nanocomposites were characterized by dynamic light scattering, scanning electron microscopy, and field emission gun scanning electron microscopy. The nanocomposites were then orally administered to Wistar rats, and their absorption was determined using morphometric, histopathological, cytochemistry, transmission electron microscopy, and biochemical analysis. Results showed that despite some aggregates being formed, the nanocomposites efficiently entrapped the natural peptides, with a loading capacity of 303.62 mg (45.7%) and an entrapment efficiency of 85.3% (267.02 µmol). Histochemical and morphological analysis revealed the absence of tissue injury and cellular changes, indicating the absence of deleterious and toxic effects. Transmission electron microscopy showed the internalization of the nanocomposites in the enterocytes, and biochemical analysis indicated that natural peptides were absorbed reaching the bloodstream.

Transcriptome-based polygenic score links depression-related corticolimbic gene expression changes to sex-specific brain morphology and depression risk.

Studies in post-mortem human brain tissue have associated major depressive disorder (MDD) with cortical transcriptomic changes, whose potential in vivo impact remains unexplored. To address this translational gap, we recently developed a transcriptome-based polygenic risk score (T-PRS) based on common functional variants capturing 'depression-like' shifts in cortical gene expression. Here, we used a non-clinical sample of young adults (n = 482, Duke Neurogenetics Study: 53% women; aged 19.8 ± 1.2 years) to map T-PRS onto brain morphology measures, including Freesurfer-derived subcortical volume, cortical thickness, surface area, and local gyrification index, as well as broad MDD risk, indexed by self-reported family history of depression. We conducted side-by-side comparisons with a PRS independently derived from a Psychiatric Genomics Consortium (PGC) MDD GWAS (PGC-PRS), and sought to link T-PRS with diagnosis and symptom severity directly in PGC-MDD participants (n = 29,340, 59% women; 12,923 MDD cases, 16,417 controls). T-PRS was associated with smaller amygdala volume in women (t = -3.478, p = 0.001) and lower prefrontal gyrification across sexes. In men, T-PRS was associated with hypergyrification in temporal and occipital regions. Prefrontal hypogyrification mediated a male-specific indirect link between T-PRS and familial depression (b = 0.005, p = 0.029). PGC-PRS was similarly associated with lower amygdala volume and cortical gyrification; however, both effects were male-specific and hypogyrification emerged in distinct parietal and temporo-occipital regions, unassociated with familial depression. In PGC-MDD, T-PRS did not predict diagnosis (OR = 1.007, 95% CI = [0.997-1.018]) but correlated with symptom severity in men (rho = 0.175, p = 7.957 × 10-4) in one cohort (N = 762, 48% men). Depression-like shifts in cortical gene expression have sex-specific effects on brain morphology and may contribute to broad depression vulnerability in men.

Prenatal and pubertal exposure to 17α-ethinylestradiol cause morphological changes in the prostate of old gerbils.

This study evaluated such as exposure to ethinylestradiol during the prenatal (18th-22nd day) and pubertal (42nd-49th day) periods acts on the male ventral prostate and female prostate of 12-month old gerbils. We performed the analysis to serum hormone levels for estradiol and testosterone. The prostates were submitted to morphometric and immunohistochemical analyses. Exposure to ethinylestradiol during these developmental periods decreased the testosterone serum levels in males and increased the estradiol serum levels in females. Morphologically, prostate intraepithelial neoplasia and disorders in the arrangement of the fibrous components were observed in the prostate glands of both sexes of gerbil exposed to ethinylestradiol during development periods. In the male prostate, the ethinylestradiol promoted decreased in the frequency of positive epithelial cell for androgen receptor (AR) and increased the frequency of positive stromal cell for estrogen receptor α. However, in the female prostate, this synthetic estrogen caused AR upregulation and increased cell proliferation. This study shows that the exposure to ethinylestradiol during development phases alters the morphology and the hormonal signaling in the male and female prostates of old gerbils, confirming the action of ethinylestradiol as endocrine disruptor.

Genetic Diversity and Population Genetic Structure of a Guzerá (Bos indicus) Meta-Population.

The Brazilian Guzerá population originated from a few founders introduced from India. These animals adapted well to the harsh environments in Brazil, were selected for beef, milk, or dual-purpose (beef and milk), and were extensively used to produce crossbred animals. Here, the impact of these historical events with regard to the population structure and genetic diversity in a Guzerá meta-population was evaluated. DNA samples of 744 animals (one dairy, nine dual-purpose, and five beef herds) were genotyped for 21 microsatellite loci. Ho, He, PIC, Fis, Fit, and Fst estimates were obtained considering either farms or lineages as subpopulations. Mean Ho (0.73) and PIC (0.75) suggest that genetic diversity was efficiently conserved. Fit, Fis and Fst values (95% CI) pointed to a low fixation index, and large genetic diversity: Fit (Farms = 0.021-0.100; lineages = 0.021-0.100), Fis (Farms = -0.007-0.076; lineages = -0.014-0.070), and Fst (Farms = 0.0237-0.032; lineages = 0.029-0.038). The dual-purpose herds/selection lines are the most uniform subpopulation, while the beef one preserved larger amounts of genetic diversity among herds. In addition, the dairy herd showed to be genetically distant from other herds. Taken together, these results suggest that this Guzerá meta-population has high genetic diversity, a low degree of population subdivision, and a low inbreeding level.

The prostate of the bat Artibeus lituratus: Seasonal variations, abiotic regulation, and hormonal control.

The prostate is an important gland that contributes to the male reproductive process, producing secretions that are essential for maintaining ideal conditions for the survival of sperm. Studies indicate a wide variation in the occurrence, morphology, and physiology of this gland in mammals, especially in bats, with this variation being related not only to the number of regions and their degree of compaction/lobulation but also to fluctuations in their functioning throughout the year. Thus, the aim of this study was to evaluate the annual morphological and physiological variations of the male prostate of Artibeus lituratus and analyze their responses to annual abiotic variations and hormonal control. Sixty sexually adult males of A. lituratus were analyzed in this study, with five specimens collected monthly. Blood samples were submitted to serum hormone measurements and the prostates were morphologically, morphometrically, and immunohistochemically analyzed. The results indicated that the two prostatic regions (ventral and dorsal) of A. lituratus had different morphology, as well as different physiology and regulation. Annual fluctuations in abiotic factors seemed to influence the dorsal region more than the ventral region. Conversely, variations on testicular factors, such as testosterone and estradiol, influenced the ventral region more than the dorsal region. Despite these differences, both prostatic regions were strongly synchronized to the main reproductive peak of the species in September. The holocrine pattern of the ventral prostate was not directly affected by abiotic factors or by factors released by the testes.

The hormonal control of the uterus of the bat Myotis nigricans during its different reproductive phases: emphasis on progesterone and estradiol.

Myotis nigricans is a species of bat from the Vespertilionidae family that is endemic of the Neotropical region. Its insectivorous feeding habit plus its large range of prey species, great geographical dispersion, wide colonies, and anthropomorphized behavior make this species an important ecological agent that acts in the control of nocturnal insects. Reproductively, M. nigricans presents geographic variations, having different patterns of reproduction according to its geographical location. Despite these extremely interesting characteristics, no more detailed study of the hormonal control of the reproduction of this species has been conducted. Therefore, the aim of the present study was to evaluate the variations in serum hormone concentrations and in uterine hormonal control of this bat during its different reproductive phases. Twenty adult females were collected, divided into four (4) sample groups, according to the reproductive status (nonreproductive, initial, and advanced pregnancy and lactating), and submitted to hormone dosage and immunohistochemical analyses. The results demonstrated that the uterus of M. nigricans is strongly regulated by the interaction/cross-talk between serum concentrations of estradiol (E2) and progesterone with their respective hormone receptors. Significant increases in the concentration of E2 and progesterone are needed to regulate the early pregnancy. The persistence of the corpus luteum throughout pregnancy is necessary, since its placenta does not express aromatase. The expressions of ERα and PR appear to be synchronized in order to coordinate a large portion of the processes that occur inside the uterus of M. nigricans during pregnancy and lactation.

Relationships among Indicators of Metabolism, Mammary Health and the Microbiomes of Periparturient Holstein Cows.

During the period called "transition", from the ceasing of milk production to the reestablishment of full milk production, it is postulated that the microbiota of cows undergo changes in composition driven by the fluxes in systemic energetics and that these changes appear to impact the health of cows. The primary objective of this study was to document the make-up of the microbiota in the mammary gland compared with those in the vagina and in feces in an attempt to determine any correlations between the composition of the microbiota, the impact of blood indicators of energetic metabolites and the health of the mammary gland at the time of calving. Samples were collected from 20 Holstein dairy cows immediately following calving to assess their general health and measure the microbiomes associated with each cow using 16S rRNA sequencing. The results indicated that the microbiomes found within each maternal niche were different. A set of significant negative associations between the blood energetic biomarkers (NEFAs, BHB, triglycerides and cholesterol) and the taxa Pseudomonas, Christensenellaceae and Methanobrevibacter were observed in this study. In contrast, Escherichia and Romboutsia were positively correlated with the same energetic metabolites. Therefore, it was concluded that there appears to be a set of relationships between the microorganisms that colonize several niches of cows and the sufficiency of systemic energy metabolism. Furthermore, both the microbiome and energy dynamics impact the health of the mammary gland of the host.

Novel polygenic risk score as a translational tool linking depression-related changes in the corticolimbic transcriptome with neural face processing and anhedonic symptoms.

Convergent data from imaging and postmortem brain transcriptome studies implicate corticolimbic circuit (CLC) dysregulation in the pathophysiology of depression. To more directly bridge these lines of work, we generated a novel transcriptome-based polygenic risk score (T-PRS), capturing subtle shifts toward depression-like gene expression patterns in key CLC regions, and mapped this T-PRS onto brain function and related depressive symptoms in a nonclinical sample of 478 young adults (225 men; age 19.79 +/- 1.24) from the Duke Neurogenetics Study. First, T-PRS was generated based on common functional SNPs shifting CLC gene expression toward a depression-like state. Next, we used multivariate partial least squares regression to map T-PRS onto whole-brain activity patterns during perceptual processing of social stimuli (i.e., human faces). For validation, we conducted a comparative analysis with a PRS summarizing depression risk variants identified by the Psychiatric Genomics Consortium (PGC-PRS). Sex was modeled as moderating factor. We showed that T-PRS was associated with widespread reductions in neural response to neutral faces in women and to emotional faces and shapes in men (multivariate p < 0.01). This female-specific reductions in neural response to neutral faces was also associated with PGC-PRS (multivariate p < 0.03). Reduced reactivity to neutral faces was further associated with increased self-reported anhedonia. We conclude that women with functional alleles mimicking the postmortem transcriptomic CLC signature of depression have blunted neural activity to social stimuli, which may be expressed as higher anhedonia.

Ethinylestradiol and its effects on the macrophages in the prostate of adult and senile gerbils.

Prenatal and neonatal exposure to estrogenic compounds, such as ethinylestradiol (EE), promotes a variety of developmental disorders, including malformations and alterations in the morphology of glands, such as the prostate gland. Therefore, the aim of this study was to evaluate the morphological effects of neonatal exposure to EE on prostatic tissue and on the identification and quantification of gerbil gland macrophages in adult and senile Mongolian gerbils. The animals were exposed to EE (10 µg/kg/day) and to the vehicle, mineral oil (100 µL) (control group) during the first 10 days of postnatal life (lactation period). Adult gerbils were euthanized at 120 days and senile gerbils at 12 months of age. Our findings permitted verification of the presence of areas with proliferative foci in the prostate glandular portions in the adult and senile animals exposed to EE. There was also an increase in macrophages in the prostate tissue of adult and senile gerbils; these cell types alter the stromal microenvironment and possibly modify the interactions between the epithelium and stroma. Neonatal exposure to EE changes the pattern of prostatic development, leading to alterations in the arrangement of cells, including macrophages, and may be related to the onset of proliferative disorders in the prostate of adult gerbils and during aging.

Evaluation of the uterine hormonal control of the bat Artibeus lituratus during the different phases of its reproductive cycle.

Artibeus lituratus is a frugivorous bat that directly assists in the restoration of degraded habitats through the effective dispersion of seeds and fruits. Given its great importance, this work aimed to evaluate the uterine hormonal control of A. lituratus during its different reproductive phases. The uteri of 30 sexually mature adult females, five specimens for each of the six sample groups (NON, nonreproductive; P1, initial pregnancy; P2, intermediate pregnancy; P3, advanced pregnancy; LAC, lactating; P + LAC, pregnant-lactating), were submitted to analyses of serum estradiol and progesterone concentrations, in addition to immunohistochemical analyses. Both estradiol and progesterone, gradually increased during pregnancy, with a marked significant increase in P3 females. Both returned to low levels in LAC-females; however, estradiol levels decreased further in P + LAC-females, while progesterone increased in the same group. In general, signs indicative of aromatase expression were observed in the endometrium of all analyzed groups and in the placenta of bats in the gestation groups. Similarly, ERα and PR were expressed in the myometrium, endometrium and placenta at varying levels of intensity. The results indicate that the uterine microenvironment of A. lituratus is directly regulated by serum concentrations of estradiol and progesterone, and fluctuations in these concentrations control morphological and physiological changes of this organ during different phases of the reproductive cycle. RESEARCH HIGHLIGHTS: Increases in serum concentrations of estradiol and progesterone coordinate the gestational period of A. lituratus. Estradiol activates ERα, stimulating cell proliferation in the uterus, in addition to activating the expression of PR, which trigger the quiescence of the myometrium and stimulation of the secretion and differentiation of the endometrium. Results showed several similarities to humans, indicating the use of A. lituratus as an animal model in reproductive studies.

Differences between male and female prostates in terms of physiology, sensitivity to chemicals and pathogenesis-A review in a rodent model.

The prostate is a gland that is not exclusively present in males, being also found in females of several mammalian species, including humans. There is evidence that the prostate in both sexes is affected by the same pathologies such as prostatitis, benign alterations and even cancer. In view of the difficulties of manipulating the prostate gland, the Mongolian gerbil (Meriones unguiculatus), a rodent species with high incidence of functional prostates in females, is widely used in studies of the female prostate. However, despite knowing much about the similarities between the female and male prostate, little emphasis has been placed on the differences between them. This review investigates the intersex differences in prostate development, physiology and pathogenesis. The female prostate develops earlier than in males and studies indicate that it is more sensitive to oestrogens than the male prostate, as well as being more sensitive to exposure to xenoestrogens, such as Bisphenol A and methylparaben, with a higher susceptibility to benign lesions in the adult and senile prostate than in males. In addition, the female prostate is impacted by pregnancy and the oestrous cycle, and is also dependent on progesterone. The peculiarities of the female prostate raise concerns about the risk of it undergoing neglected changes as a result of environmental chemicals, since safe dosages are established exclusively for the male prostate.

Stimulation of the ACE2/Ang-(1-7)/Mas axis in hypertensive pregnant rats attenuates cardiovascular dysfunction in adult male offspring.

The aim of this study was to investigate whether treatment with diminazene aceturate (DIZE), a putative ACE2 activator, or with angiotensin-(1-7) during pregnancy could attenuate the development of cardiovascular dysfunction in the adult offspring of spontaneously hypertensive rats (SHRs). For this, pregnant SHRs received DIZE or Ang-(1-7) throughout gestation. The systolic blood pressure (SBP) was measured in the male offspring from the 6th to16th weeks of age by tail-cuff plethysmography. Thereafter, the left ventricular contractile function and coronary reactivity were evaluated by the Langendorff technique. Samples of the left ventricles (LVs) and kidneys were collected for histology and western blot assay in another batch of adult rat offspring. Maternal treatment with DIZE or Ang-(1-7) during pregnancy attenuated the increase in SBP in adult offspring. In addition, both DIZE and Ang-(1-7) treatments reduced the cardiomyocyte diameter and fibrosis deposition in the LV, and treatment with Ang-(1-7) also reduced the fibrosis deposition in the kidneys. Maternal treatment with DIZE, as well as Ang-(1-7), improved the coronary vasodilation induced by bradykinin in isolated hearts from adult offspring. However, no difference was observed in the contractile function of the LVs of these animals. The expression levels of AT1 and Mas receptors, ACE, ACE2, SOD, and catalase in the LV were not modified by maternal treatment with Ang-(1-7), but this treatment elicited a reduction in AT2 expression. These data show that treatment with DIZE or Ang-(1-7) during gestation promoted beneficial effects of attenuating hypertension and cardiac remodeling in adult offspring.

Short-term exposure to chrysin promotes proliferative responses in the ventral male prostate and female prostate of adult gerbils.

Chrysin (5,7-dihydroxyflavone) is a bioactive compound found in different fruits, vegetables, honey and propolis. This flavone has been suggested for the treatment of reproductive dysfunction, mainly because of its antioxidant and hormonal properties. However, the effects of this polyphenol on the prostate are still poorly understood. The purpose of this study was to evaluate the effects of short-term chrysin exposure on the ventral male and female prostates of adult gerbils. To evaluate the androgenic potential of chrysin, gerbils were also exposed to testosterone. Male and female gerbils were exposed to chrysin (50 mg/kg/day, orally) or testosterone cypionate (1 mg/kg/week, subcutaneously) for 3, 7 and 21 days. Prostates were dissected for morphological, stereological and immunohistochemical analyses. Serum levels of testosterone and 17ß-estradiol were measured by ELISA. Serum testosterone levels were not increased by chrysin supplementation in males or females. However, only females treated with chrysin for 21 days showed an increase in estradiol levels. Increased androgen receptor immunoreactivity, higher proliferation rates and glandular hyperplasia were observed in male and female prostates for all chrysin treatment times. Additionally, increased oestrogen receptor alpha immunoreactivity was observed in all chrysin-treated females. Although chrysin and testosterone promoted similar morphological changes in the gerbil prostate, chrysin supplementation was less deleterious to prostate health, since it resulted in lower incidence of hyperplasia and an absence of neoplastic foci.