Survivin in Breast Cancer: A Review.

Breast cancer is the most frequently diagnosed cancer in women and ranks second among causes for cancer-related death in women. Gene technology has led to the recognition that breast cancer is a heterogeneous disease composed of different biological subtypes, and genetic profiling enables the response to chemotherapy to be predicted. This fact emphasizes the importance of selecting sensitive diagnostic and prognostic markers in the early disease stage and more efficient targeted treatments for this disease. One such prognostic marker appears to be survivin. Many studies have shown that survivin is strongly expressed in different types of cancers. Its overexpression has been demonstrated in breast cancer, and high activity of the survivin gene has been associated with a poor prognosis and worse survival rates.

Para-occupational exposure to pesticides, PON1 polymorphisms and hypothyroxinemia during the first half of pregnancy in women living in a Mexican floricultural area.

BACKGROUND: Adequate maternal thyroxine (T4) concentrations during the first half of pregnancy are fundamental to the embryo's or fetus' neural development. Organophosphate pesticides (OP) can act as thyroid disruptors and genetic polymorphisms for paraoxonase 1 (PON1), an enzyme that detoxifies OP, could be involved in individual's susceptibility to them. We assessed the association between para-occupational exposure to pesticides, including OP, during pregnancy and maternal hypothyroxinemia, as well as the potential genetic susceptibility conferred by PON1 polymorphisms. METHODS: We analyzed information from 381 healthy pregnant women (< 17 gestational weeks), who lived in a floricultural region of Mexico where pesticides, including OP, are routinely used. Women who were para-occupationally exposed to pesticides were those whose partner had an occupation involving contact with these products. Thyroid-Stimulating Hormone (TSH) and free T4 concentrations were determined using ELISA, and hypothyroxinemia was defined as free T4 concentrations <0.76 ng/dL. PON1192QR, PON155LM and PON1-108CT polymorphisms were determined through Polymerase Chain Reaction (PCR). The association between para-occupational exposure and genetic polymorphisms and hypothyroxinemia was estimated using logistic regression models. RESULTS: One hundred and sixty two women (42.52%) were classified as para-occupationally exposed to pesticides. Hypothyroxinemia prevalence was 54%, and it was not significantly associated with pesticide para-occupational exposure (OR: 1.21 95% CI 0.75-1.94). Independently of para-occupational exposure, the likelihood of hypothyroxinemia was higher among women who were carriers of PON155MM than in those with PON155LL genotype (OR MM vs LL: 3.03; 95%CI 1.62, 5.70). PON1192 RR (OR RR vs QQ: 1.72; 95%CI 0.93, 3.17) and PON1-108TT (OR TT vs CC: 1.60; 95%CI 0.90, 2.70) genotypes were marginally associated with hypothyroxinemia. No significant interaction was observed between pesticides para-occupational exposure and PON1 polymorphisms. CONCLUSIONS: These results suggest that PON1 polymorphisms could affect thyroid function during pregnancy in women living in areas where pesticides, including OP, are routinely used. Low exposure variability in this population, could be a possible explanation for the lack of association between para-occupational exposure and thyroid function.

Toxic Effect of Cadmium, Lead, and Arsenic on the Sertoli Cell: Mechanisms of Damage Involved.

Over the past decades, an increase has been described in exposure to environmental toxins; consequently, a series of studies has been carried out with the aim of identifying problems associated with health. One of the main risk factors is exposure to heavy metals. The adverse effects that these compounds exert on health are quite complex and difficult to elucidate, in that they act at different levels and there are various signaling pathways that are implicated in the mechanisms of damage. The Sertoli cells plays a role of vital importance during the process of spermatogenesis, and it has been identified as one of the principal targets of heavy metals. In the present review, cadmium, lead, and arsenic are broached as altering the physiology of the Sertoli cells, citing mechanisms that have been cited in the literature.

In Vitro Evaluation of Damage by Heavy Metals in Tight and Gap Junctions of Sertoli Cells.

The Sertoli cell plays a vital role during the spermatogenesis process and has been identified as one of the main targets of the toxic action of heavy metals on the seminiferous epithelium. In the present work, the effect of lead (Pb), Arsenic (As), and Cadmium (Cd) in primary cultures of Sertoli cells was analyzed by measuring the expression of the genes Cldn11, Ocln, and Gja1 that participate in the tight and gap junctions, which are responsible for maintaining the blood-testis barrier. Sertoli cells were isolated from the testes of Wistar rats. Sertoli cell cultures were exposed separately and at the same concentrations of three heavy metals for 48 h. Subsequently, gene expression was measured by real-time polymerase chain reaction. In the morphological analysis of the cultures, after 24 h, the cultures exposed to Cd showed greatest detachment of the monolayer, followed by those exposed to As and Pb. As for gene expression patterns, As induced a decrease in the expression of the Cldn11 gene at 24 and 48 h (p < 0.01) and in that of Ocln at 24 (p < 0.001) and 48 h (p < 0.01), whereas Cd induced overexpression of the Gja1 gene from day 1 of exposure (p < 0.001) and subexpression of the Ocln gene (p < 0.05) at 24 h. Because each of these three metals generated different expression patterns in the three genes, we can postulate that the mechanisms of damage that they induce are different; therefore, the effect that they exert on the Sertoli cell occurs through different pathways, generating changes in structural proteins, altering Sertoli cell morphology, and compromising its function in the regulation of the spermatogenesis process.

Effect of exposure to p,p´-DDE during the first half of pregnancy in the maternal thyroid profile of female residents in a Mexican floriculture area.

BACKGROUND: Dichlorodiphenyldichloroethene (p,p´-DDE), the main metabolite of dichlorodiphenyltrichloroethane (DDT), has been associated with changes in human thyroid hormone levels. Maternal thyroid hormones are essential for adequate fetal neurodevelopment during the first half of pregnancy. OBJECTIVE: To evaluate the association between maternal p,p´-DDE concentration and the maternal thyroid profile during the first half of pregnancy. MATERIALS AND METHODS: We analyzed the information of 430 pregnant women from a Mexican floriculture area, with a gestational age ≤16 weeks. By questionnaire, we obtained sociodemographic, reproductive, and life-style, information. Serum concentrations of thyroid stimulating hormone (TSH), and total and free T3 and T4 were determined by means of Enzyme-Linked ImmunoSorbent Assay (ELISA). p,p´-DDE was analyzed by Gas Chromatography. The association between p,p´-DDE and thyroid profile was assessed through linear and logistic regression models. RESULTS: Thirty eight percent of women had p,p´-DDE levels below the Limit of Detection and 12.3% below the Limit of Quantification. Within the quantifiable range, median was 53.03ng/g. TSH >2.5 mIU/L was present in 9.3% of women; 47.7% had isolated hypothyroxinemia; 3.5% had subclinical hypothyroidism, and 5.8% had overt hypothyroidism. We observed a significant positive association between quantifiable p,p´-DDE and total T3 serum levels in comparison with those with concentrations below the Limit of Detection (ß=0.19; 95% CI=0.06, 0.34). There were no significant associations with other hormones of the thyroid profile or with clinical diagnosis. CONCLUSIONS: Our findings suggest that p,p´-DDE exposure, even at low concentrations, could disrupt thyroid homeostasis during pregnancy.

Chronic environmental exposure to lead affects semen quality in a Mexican men population.

BACKGROUND: Male infertility is affected by several factors. Lead is one of the heavy metals more bioavailable than usually modifies the sperm quality in humans. OBJECTIVE: The aim of this study was to establish the role of lead in semen quality in environmentally exposed men. MATERIALS AND METHODS: Semen and blood samples were obtained from two groups: the exposed group (EG=20) and the non-exposed group (NEG=27). Two semen aliquots were used, one to evaluate spermatic quality and the other for lead determination. Blood (PbB) and semen lead (PbS) determination was performed by atomic absorption spectrophotometry. RESULTS: The PbB concentration was significantly greater in the EG, 10.10±0.97 µgdL-1 than in the NEG, 6.42±0.38 µgdL-1 (p<0.01), as well as the PbS concentration, with 3.28±0.35 and 1.76±0.14µgdL-1 in the EG and NEG respectively (p=0.043). A significant correlation between PbS and PbB concentration in the EG was found (r=0.573, p=0.038). Overall, the spermatic quality was lower in the EG than in the NEG. Specifically, there were significant differences in the spermatic concentration [EG=43.98±6.26 and NEG=68.78±8.51X10(6) cellmL-1 (p<0.01)], motility [EG=49±7 and NEG=67±4% (p=0.029)], viability [EG=36.32±3.59 and NEG=72.12±1.91% (p<0.01)] and abnormal morphology [EG=67±18 and NEG=32±12% (p<0.01)]. In the immature germ cells (IGC) concentration differences were found only for A cells (EG=8.1±1.1x100 and NEG=3.2±1.9X100 spermatozoa) (p<0.01) and for Sab cells (EG=3.4±2.2x100 and NEG=1.1±1.0X100 spermatozoa) (p=0.041). CONCLUSION: These results suggest that chronic environmental exposure to low levels of lead adversely affect the spermatic quality.

Symptoms at postmenopause: genetic and psychosocial factors.

OBJECTIVE: Menopause symptoms result from the interaction of estrogen deprivation, psychosocial influences, and genetic factors. We examined the influence of stress and of estrogen receptor-α (ER-α; PvuII and XbaI) and serotonin transporter (5-HTT) polymorphisms on symptoms at postmenopause. METHODS: We studied 290 urban women from three cities in Mexico. General characteristics, menopause symptoms, and scores of perceived stress, effort-reward imbalance, dominance, and submission were collected. A fasting blood sample was obtained for hormone measurements and genotypification. RESULTS: Women had a mean ± SD age of 54.4 ± 4.5 years and BMI of 29.5 ± 4.9 kg/m. The frequency of hot flashes was 75.5%; vaginal dryness, 57.8%; and diminished sexual interest, 78.7%. Follicle-stimulating hormone and estradiol levels were 59 ± 27 mIU/mL and 22 ± 29 pg/mL, respectively. Women from Torreón had higher schooling and less parity but higher scores for depression and lower submission. Hot flashes were more frequent in women from León. Genotype distribution was similar among cities. Lower scores for dominance were found in women with the pp and xx ER-α genotypes. Increased smoking habit was found for the SS genotype of 5-HTT. Factors significantly associated with symptoms were years since menopause, with hot flashes (negative), and with diminished sexual interest (positive); dominance was negatively associated with depression, perceived stress, and vaginal dryness; submission was positively associated with depression, perceived stress, anxiety, and hot flashes; and effort-reward imbalance was positively associated with anxiety, hot flashes, and perceived stress. CONCLUSIONS: Symptoms at postmenopause were associated mainly with dominance, submission, and effort-reward imbalance. The pp genotype of ER-α showed lower scores of dominance.

Lead-, cadmium-, and arsenic-induced DNA damage in rat germinal cells.

Toxic agents can interfere with the male reproductive system at many targets. One of the major unresolved questions concerning male infertility is identification of its molecular origins. Clinical and animal studies indicate that abnormalities of spermatogenesis result from exposure to three toxic metals (lead acetate, cadmium chloride, and arsenic trioxide), but the effects on primary spermatocyte DNA of the male rat after chronic exposure to these metals have not been identified. The aims of this study were to analyze, in three independent experiments, the DNA damage induced by lead (Pb), cadmium (Cd), and arsenic (As) in rat germinal cells during three time periods, and to determine the relationship between DNA damage and blood Pb, blood Cd, and urine As levels. For lead acetate and cadmium chloride experiments, blood was collected by cardiac puncture, while for arsenic trioxide a 24-h urine sample was collected. Afterward, the animals were sacrificed by decapitation. Pachytene spermatocytes from rat testes were purified by trypsin digestion followed by centrifugal elutriation. After establishment of cell purity and viability, DNA damage (tail length) was measured employing a single cell gel/comet assay. Significant DNA damage was found in primary spermatocytes from rats with chronic exposure (13 weeks) to toxic metals. In conclusion, these findings indicate that exposure to toxic metals affects primary spermatocyte DNA and are suggestive of possible direct testicular toxicity.

Dichlorodiphenyldichloroethylene concentrations in umbilical cord of newborns and determinant maternal factors.

OBJECTIVE: The aim was to identify exposure levels to dichlorodiphenyltrichloroethane (DDT) and to assess maternal factors as determinants of the serum dichlorodiphenyldichloroethylene (DDE) concentration in umbilical cord in newborns from the Mexican Pacific coastal area of Oaxaca State. MATERIALS AND METHODS: A cross-sectional study was conducted of 86 paired mothers and newborns from the Oaxaca community of Pochutla. Blood and umbilical cord blood samples were collected to determine DDT and DDE by GC. Information concerning possible determinant factors with regard to pesticide concentration was obtained by means of a questionnaire. RESULTS: A positive correlation between maternal and umbilical cord serum DDE concentration was observed (geometric mean of 7.69 microg g(-1) and 7.29, respectively). Multiple analyses showed that significant maternal factors related to umbilical cord serum DDE concentrations were: always having lived in the same community; low to high socioeconomic strata; accumulated breast-feeding time. CONCLUSIONS: The determinant factors observed in this study must be considered in future studies for the quantification of organochlorine concentration. In addition, these factors must be taken into account when preventive actions to minimize in utero exposure to these pesticides are carried out.