Chronic alcohol intake upregulates hepatic expression of carotenoid cleavage enzymes and PPAR in rats

Excessive and chronic alcohol intake leads to a lower hepatic vitamin A status by interfering with vitamin A metabolism. Dietary provitamin A carotenoids can be converted into vitamin A mainly by carotenoid 15,15′-monooxygenase 1 (CMO1) and, to a lesser degree, carotenoid 9′10′-monooxygenase 2 (CMO2). CMO1 has been shown to be regulated by several transcription factors, such as the PPAR, retinoid X receptor, and thyroid receptor (TR). The regulation of CMO2 has yet to be identified. The impact of chronic alcohol intake on hepatic expressions of CMO1 and CMO2 and their related transcription factors are unknown. In this study, Fischer 344 rats were pair-fed either a liquid ethanol Lieber-DeCarli diet (n = 10) or a control diet (n = 10) for 11 wk. Hepatic retinoid concentration and expressions of CMO1, CMO2, PPARγ, PPARα, and TRβ as well as plasma thyroid hormones levels were analyzed. We observed that administering alcohol decreased hepatic retinoid levels but increased mRNA concentrations of CMO1, CMO2, PPARγ, PPARα, and TRβ and upregulated protein levels of CMO2, PPARγ, and PPARα. There was a positive correlation of PPARγ with CMO1(r = 0.89; P<0.0001) and both PPARγ and PPARα with CMO2 (r = 0.72, P< 0.001 and r = 0.62, P< 0.01, respectively). Plasma thyroid hormone concentrations did not differ between the control rats and alcohol-fed rats. This study suggests that chronic alcohol intake significantly upregulates hepatic expression of CMO1 and, to a much lesser extent, CMO2. This process may be due to alcohol-induced PPARγ expression and lower vitamin A status in the liver. © 2010 American Society for Nutrition.

The expression of aquaporins 1 and 9 in adult rat epididymis is perturbed by chronic exposure to ethanol

Aquaporins (AQPs), notably AQP-1 and AQP-9, may contribute to reabsorption of fluid and solute across the epididymis. Ethanol is related to be a toxicant affecting directly or indirectly the epididymis and the sperm motility. This study examined the expression of AQP-1 and AQP-9 in adult epididymis of the UChA and UChB 10% (v/v) ethanol-preferring rats, focusing the ethanol-induced hormonal disturbances upon the regulation of these AQPs. Chronic ethanol intake significantly decreased body weight, while UChA and UChB rats displayed a marked loss of epididymal weights. Both ethanol-consuming animals had a severe reduction of testosterone levels, whereas LH and 17β-estradiol were unchanged. Throughout the epididymis, a strong reaction to AQP-1 was observed in myoid and endothelial cells of the UChB ethanol-preferring rats, differently from a moderate intensity in the initial segment of the UChA rats. In addition, AQP-9 showed a strong immunoreaction in the apical membrane of principal cells at initial segment. In cauda epididymis, the level of AQP-9 was reduced along the microvillus projections in both UChA and UChB rats compared to controls. We conclude that chronic ethanol consumption modulates the androgen levels, thereby modifying the expression pattern of AQP-1 and 9 in the epididymis. © 2011 Elsevier Ltd.

Agonistas do GnRH, antagonistas do GnRH e a reprodução assistida: Análogos do GnRH x fertilização in vitro

The agonists of gonadotropin-releasing hormone (GnRH) were introduced in ovarian stimulation for in vitro fertilization to avoid a premature surge of luteinizing hormone. Although they are accompanied by some disadvantages, GnRH agonists have become well accepted in clinical practice, and their use is associated with increased rates of pregnancy. The development of GnRH antagonists capable of blocking the pituitary immediately offered a therapeutic option. Comparative studies between the two analogs have suggested that the use of antagonists is associated with a shorter duration of ovulatory stimulus and a decreased incidence of ovarian hyperstimulation syndrome, while the type of GnRH analogues used show no significant effects on the rates of pregnancy and live birth. However, GnRH agonists have other applications in assisted reproductive technology cycles than the pituitary downregulation.

Diferenças sazonais no padrão endócrino e ovariano do ciclo estral de novilhas bos taurus indicus (Nelore)

Estrous cycle of eight Nelore heifers were evaluated during different seasons of the year (autumn n=11; winter n=8; spring n=9 and summer n=9) with daily count and measurement of follicles ≥3mm, blood was collected every 12h for LH and progesterone (P4), and after estrous every 3h for LH peak. Five ovariectomized heifers were injected with 17β-estradiol (2μg/kg) every season and blood samples collected every 3h (for 30h) thereafter for LH quantification. The monthly percent body weight difference (Δ%) did not vary among seasons. P4 concentration was higher (p<0.01) and follicle number lower during autumn and summer compared to winter and spring. During winter there were more estrous cycles with three and during summer only cycles with two follicular waves (p<0.01). As LH secretion did not vary despite P4 concentration and as there was negative correlation between higher P4 values and daily percentile variation of photoperiod (Δ%, p<0.01; r= -0.45) it is possible to suppose that there is seasonal variation on luteal cell sensitivity to LH. In the ovariectomized Nelore heifers, the LH basal concentration (without estradiol stimulus, p=0.02) and the LH response to estradiol (p<0.01) were lower during summer, leading to the hypothesis that there is seasonal variation of hypothalamic sensitivity to estradiol. According to the present experiment there are suggestions of seasonal reproduction in Nelore heifers.

Evaluation of the hypothalamus-pituitary axis response to exogenous GnRH, estradiol benzoate, And LH during the postpartum period in Nellore cows

The objective was to evaluate when the LH reserve was re-established in postpartum Nellore (Bos indicus) cows by evaluating the response of the hypothalamic-pituitary axis responsiveness to exogenous GnRH or estradiol benzoate (EB). Additionally, we tested the influence of dietary supplementation (SUPL) and calf removal (CR) on the duration of postpartum anestrus. Ninety multiparous lactating Nellore cows were randomly assigned to eight groups. The EB and GnRH groups received 1.0 mg EB (N = 7), and 50 μg lecireline (N = 16), respectively. Additional cows were given the same hormones, and subjected to either nutritional supplementation (EB-SUPL, N = 9; GnRH-SUPL, N = 16), or calf removal at 72 hours after calving (EB-CR, N = 4; GnRH-CR, N = 13). The remaining two groups were the LH (12.5 mg, N = 14) and control groups (saline, N = 11). Hormones were administered weekly from 7 (±5) days postpartum to first ovulation (detection of a CL during a weekly ultrasonographic examination). Blood samples were collected just before and 2 hours (GnRH, LH, and control groups) or 18 hours (EB groups) after hormone or saline (control) administration. Ovulation occurred as early as 15 days postpartum in the GnRH group. The mean ± SEM intervals (days) from calving to first ovulation were EB, 87.7 ± 4.2; EB-CR, 20.3 ± 1.2; EB-SUPL, 60.3 ± 3.2; GnRH, 40.4 ± 2.1; GnRH-CR, 21.0 ± 1.1; GnRH-SUPL, 26.4 ± 1.1; LH, 35.6 ± 1.1; and control, 60.9 ± 2.1. We concluded that there was sufficient LH in the pituitary gland (of Nellore cows) from the second week postpartum to induce ovulation in response to exogenous GnRH. Additionally, calf removal and nutritional supplementation reduced, by 2 to 4 weeks, the interval from calving to an LH increase and ovulation induced by GnRH or EB. © 2013.

Genomic and phenotypic profiles of two Brazilian breast cancer cell lines derived from primary human tumors

Breast cancer is the most common type of cancer among women worldwide. Research using breast cancer cell lines derived from primary tumors may provide valuable additional knowledge regarding this type of cancer. Therefore, the aim of this study was to investigate the phenotypic profiles of MACL-1 and MGSO-3, the only Brazilian breast cancer cell lines available for comparative studies. We evaluated the presence of hormone receptors, proliferation, differentiation and stem cell markers, using immunohistochemical staining of the primary tumor, cultured cells and xenografts implanted in immunodeficient mice. We also investigated the ability of the cell lines to form colonies and copy number alterations by array comparative genomic hybridization. Histopathological analysis showed that the invasive primary tumor from which the MACL-1 cell line was derived, was a luminal A subtype carcinoma, while the ductal carcinoma in situ (DCIS) that gave rise to the MGSO-3 cell line was a HER2 subtype tumor, both showing different proliferation levels. The cell lines and the tumor xenografts in mice preserved their high proliferative potential, but did not maintain the expression of the other markers assessed. This shift in expression may be due to the selection of an 'establishment' phenotype in vitro. Whole-genome DNA evaluation showed a large amount of copy number alterations (CNAs) in the two cell lines. These findings render MACL-1 and MGSO-3 the first characterized Brazilian breast cancer cell lines to be potentially used for comparative research. © 2013 Spandidos Publications Ltd. All rights reserved.

Long-term effects of perinatal androgenization on reproductive parameters of male rat offspring androgenization and male rat reproduction

It is known that during sex differentiation, fetal androgens are critical determinants of the male phenotype. Although testosterone is necessary for normal development of male sexual behavior, perinatal androgen treatment can result in disruption of normal male sexual reproduction. Pregnant Wistar rats were administered either corn oil (vehicle) or testosterone propionate at 0.2 mg/kg from gestational day 12 until the end of lactation and the reproductive function of male offspring was evaluated at 90 (adulthood) and 270 (middle age) days of age. Perinatal androgenization in the rat provoked a reduction in sperm production and reserves in adulthood that did not affect fertility and did not persist at more advanced ages, as shown by the results at post-natal day 270. If perinatal androgenization promotes similar effects in humans of reproductive age, the results of the present work can impact male reproduction health, given the less efficient spermatogenesis and lower sperm reserves in the human epididymis, compared to rodents. © Georg Thieme Verlag KG Stuttgart. New York.

Índice preditor de reserva ovariana (ORPI) para controle de estimulação ovariana individualizado

Objective: to expand the evaluation of a new ovarian response prediction index (ORPI), which was based on the AMH, AFC and age, and to verify its reability as a predictor of ovarian response to stimulation in assisted reproductive technology (ART) cycles. Methods: A total of 129 patients enrolled in the ICSI programme were included. The ORPI values were calculated by multiplying the AMH level (ng/ml) by the number of antral follicles (2-9 mm), and the result was divided by the age (years) of the patient (ORPI=(AMH × AFC)/Patient age). Results: Spearman's test revealed significant correlations (P<0.0001) between the ORPI and the number of oocytes collected and the number of follicles. Logistic regression revealed that ORPI values were significantly associated with the likelihood of collecting ≥4 oocytes (OR=45.56), ≥4 MII oocytes (OR=6.01) and ≥15 oocytes (OR=6.15; P<0.0001). Based on the ROC curves, the ORPI accurately predicted a low ovarian response (<4 oocytes retrieved; area under the curve (AUC):0.91), collection of ≥4 MII oocytes (AUC:0.85) and an excessive ovarian response (≥15 oocytes retrieved; AUC:0.89). Conclusions: The ORPI exhibited an excellent ability to predict a low ovarian response and a good ability to predict a collection of ≥ 4 MII oocytes, an excessive ovarian response. The ORPI might be used to improve the cost-benefit ratio of ovarian stimulation regimens by guiding the selection of medications and by modulating the doses and regimens according to the actual needs of the patients. © Todos os direitos reservados a SBRA - Sociedade Brasileira de Reprodução Assistida.

Detecting Loci under Recent Positive Selection in Dairy and Beef Cattle by Combining Different Genome-Wide Scan Methods

As the methodologies available for the detection of positive selection from genomic data vary in terms of assumptions and execution, weak correlations are expected among them. However, if there is any given signal that is consistently supported across different methodologies, it is strong evidence that the locus has been under past selection. In this paper, a straightforward frequentist approach based on the Stouffer Method to combine P-values across different tests for evidence of recent positive selection in common variations, as well as strategies for extracting biological information from the detected signals, were described and applied to high density single nucleotide polymorphism (SNP) data generated from dairy and beef cattle (taurine and indicine). The ancestral Bovinae allele state of over 440,000 SNP is also reported. Using this combination of methods, highly significant (P<3.17×10-7) population-specific sweeps pointing out to candidate genes and pathways that may be involved in beef and dairy production were identified. The most significant signal was found in the Cornichon homolog 3 gene (CNIH3) in Brown Swiss (P = 3.82×10-12), and may be involved in the regulation of pre-ovulatory luteinizing hormone surge. Other putative pathways under selection are the glucolysis/gluconeogenesis, transcription machinery and chemokine/cytokine activity in Angus; calpain-calpastatin system and ribosome biogenesis in Brown Swiss; and gangliosides deposition in milk fat globules in Gyr. The composite method, combined with the strategies applied to retrieve functional information, may be a useful tool for surveying genome-wide selective sweeps and providing insights in to the source of selection.

Evaluation of estrogenic, antiestrogenic and genotoxic activity of nemorosone, the major compound found in brown Cuban propolis

Background: Brown propolis is the major type of propolis found in Cuba; its principal component is nemorosone, the major constituent of Clusia rosea floral resins. Nemorosone has received increasing attention due to its strong in vitro anti-cancer action. The citotoxicity of nemorosone in several human cancer cell lines has been reported and correlated to the direct action it has on the estrogen receptor (ER). Breast cancer can be treated with agents that target estrogen-mediated signaling, such as antiestrogens. Phytoestrogen can mimic or modulate the actions of endogenous estrogens and the treatment of breast cancer with phytoestrogens may be a valid strategy, since they have shown anti-cancer activity.Methods: The aim of the present investigation was to assess the capacity of nemorosone to interact with ERs, by Recombinant Yeast Assay (RYA) and E-screen assays, and to determine by comet assay, if the compound causes DNA-damaging in tumoral and non-tumoral breast cells.Results: Nemorosone did not present estrogenic activity, however, it inhibited the 17-β-estradiol (E2) action when either of both methods was used, showing their antiestrogenicity. The DNA damage induced by the benzophenone in cancer and normal breast cells presented negative results.Conclusion: These findings suggest that nemorosone may have therapeutic application in the treatment of breast cancer. © 2013 Camargo et al.; licensee BioMed Central Ltd.

Involvement of pituitary gonadotropins, gonadal steroids and breeding season in sex change of protogynous dusky grouper, Epinephelus marginatus (Teleostei: Serranidae), induced by a non-steroidal aromatase inhibitor

Two experiments were performed using the aromatase inhibitor (AI) letrozole (100mg/kg) to promote sex change, from female-to-male, in protogynous dusky grouper. One experiment was performed during the breeding season (spring) and the other at the end of the breeding season (summer). During the spring, AI promoted sex change after 9weeks and the sperm produced was able to fertilize grouper oocytes. During the summer, the sex change was incomplete; intersex individuals were present and sperm was not released by any of the animals. Sex changed gonads had a lamellar architecture; cysts of spermatocytes and spermatozoa in the lumen of the germinal compartment. In the spring, after 4weeks, 11ketotestosterone (11KT) levels were higher in the AI than in control fish, and after 9weeks, coincident with semen release, testosterone levels increased in the AI group, while 11KT returned to the initial levels. Estradiol (E2) levels remained unchanged during the experimental period. Instead of decreasing throughout the period, as in control group, 17 α-OH progesterone levels did not change in the AI-treated fish, resulting in higher values after 9weeks when compared with control fish. fshβ and lhβ gene expression in the AI animals were lower compared with control fish after 9weeks. The use of AI was effective to obtain functional males during the breeding season. The increase in androgens, modulated by gonadotropins, triggered the sex change, enabling the development of male germ cells, whereas a decrease in E2 levels was not required to change sex in dusky grouper. © 2013 Elsevier Inc.

Perfil metabólico de cálcio e ósseo de pacientes soropositivos para HIV em uso ou não da terapia antirretroviral

Pós-graduação em Alimentos e Nutrição - FCFAR

Efeito da metformina em mulheres obesas com a síndrome de hiperandrogenismo-resistência insulínica-acantose nigricans

Pós-graduação em Ginecologia, Obstetrícia e Mastologia - FMB

Variação do ciclo estral de novilhas Bos taurus indicus (Nelore) em diferentes estações do ano

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Genome-wide scans to uncover loci underlying bovine reproductive biology

Pós-graduação em Medicina Veterinária - FCAV