Tributyltin and the Female Hypothalamic-Pituitary-Gonadal Disruption.

The hypothalamic-pituitary-gonadal (HPG) axis is the principal modulator of reproductive function. Proper control of this system relies on several hormonal pathways, which make the female reproductive components susceptible to disruption by endocrine-disrupting chemicals such as tributyltin (TBT). Here, we review the relevant research on the associations between TBT exposure and dysfunction of the female HPG axis components. Specifically, TBT reduced hypothalamic gonadotropin-releasing hormone (GnRH) expression and gonadotropin release, and impaired ovarian folliculogenesis, steroidogenesis, and ovulation, at least in part, by causing abnormal sensitivity to steroid feedback mechanisms and deleterious ovarian effects. This review covers studies using environmentally relevant doses of TBT in vitro (1 ng-20 ng/ml) and in vivo (10 ng-20 mg/kg) in mammals. The review also includes discussion of important gaps in the literature and suggests new avenue of research to evaluate the possible mechanisms underlying TBT-induced toxicity in the HPG axis. Overall, the evidence indicates that TBT exposure is associated with toxicity to the components of the female reproductive axis. Further studies are needed to better elucidate the mechanisms through which TBT impairs the ability of the HPG axis to control reproduction.

Placental outcomes of phthalate exposure.

Proper placental development and function relies on hormone receptors and signaling pathways that make the placenta susceptible to disruption by endocrine disrupting chemicals, such as phthalates. Here, we review relevant research on the associations between phthalate exposures and dysfunctions of the development and function of the placenta, including morphology, physiology, and genetic and epigenetic effects. This review covers in vitro studies, in vivo studies in mammals, and studies in humans. We also discuss important gaps in the literature. Overall, the evidence indicates that toxicity to the placental and maternal-fetal interface is associated with exposure to phthalates. Further studies are needed to better elucidate the mechanisms through which phthalates act in the placenta as well as additional human studies that assess placental disruption through pregnancy with larger sample sizes.

The impact of endocrine-disrupting chemical exposure in the mammalian hypothalamic-pituitary axis.

The hypothalamic-pituitary axis (HP axis) plays a critical and integrative role in the endocrine system control to maintain homeostasis. The HP axis is responsible for the hormonal events necessary to regulate the thyroid, adrenal glands, gonads, somatic growth, among other functions. Endocrine-disrupting chemicals (EDCs) are a worldwide public health concern. There is growing evidence that exposure to EDCs such as bisphenol A (BPA), some phthalates, polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and biphenyls (PBBs), dichlorodiphenyltrichloroethane (DDT), tributyltin (TBT), and atrazine (ATR), is associated with HP axis abnormalities. EDCs act on hormone receptors and their downstream signaling pathways and can interfere with hormone synthesis, metabolism, and actions. Because the HP axis function is particularly sensitive to endogenous hormonal changes, disruptions by EDCs can alter HP axis proper function, leading to important endocrine irregularities. Here, we review the evidence that EDCs could directly affect the mammalian HP axis function.

Effects of glyphosate exposure on human health: Insights from epidemiological and in vitro studies.

Glyphosate (GLY) is a broad-spectrum, post-emergent, non-selective and synthetic universal herbicide, whose commercial formulations are referred to as glyphosate-based-herbicides (GBHs). These chemicals and their metabolites can be found in soil, air, water, as well as groundwater and food products. This review summarizes to summarize current in vitro and epidemiological studies investigating the effects of GLY exposure on human health. Recent human cell studies have reported several GLY and GBH toxicological effects and have contributed to a better understanding of the deleterious consequences associated with their exposure. However, these detrimental effects are dependent on the cell type, chemical composition, as well as magnitude and time of exposure, among other factors. Moreover, the deleterious effects of GLY exposure on human health were observed in epidemiological studies; however, most of these studies have not determined the GLY dosage to confirm a direct effect. While GLY toxicity is clear in human cells, epidemiological studies investigating individuals exposed to different levels of GLY have reported contradictory data. Therefore, based on currently available in vitro and epidemiological data, it is not possible to confirm the complete safety of GLY use, which will require additional comprehensive studies in animal models and humans.

Presence of infection and analysis of HPV subtypes in girls younger than 9 years old attended at a referral service in Espírito Santo, Brazil.

Human papillomavirus (HPV) is found in adults and adolescents and is associated with genital warts and cervical cancer. However, it has been detected in girls younger than 10 years old. Currently, there are no prevention methods for this age group, since it is not considered a risk group. The aim of this study was to evaluate the presence of infection and HPV subtype in girls under 9 years old attended at a referral service in the State of Espírito Santo, Brazil. Forty-three girls younger than 9 years old had gynecological brush samples collected from vulval and perineal/anal regions. Viral detection and subtyping were done using polymerase chain reaction, restriction fragment length polymorphism and DNA sequencing. Statistics was performed using Action Stat 3.1. The mean age of girls was 6.1 years. Sexual activity and abuse were not reported by 95.3%. Family stories showed viral infection in 9.3% of mothers, 4.7% of fathers and 9.3% of caretakers. None of these were related with the children infection. In the only case of mother's gestational HPV infection, the daughter tested negative. Genital warts and infection were observed in 7% and 13.9% of the patients, respectively. Viral subtypes detected were 6, 11, 38, and 42. These results demonstrate the presence of HPV infection in girls under 9 years of age. Prevalence studies are needed in order to evaluate a possible alteration in age of vaccination policy.

ATM, BCL2, and TGFß Gene Polymorphisms as Radiotherapy Outcome Biomarkers in Head and Neck Squamous Cell Carcinoma Patients.

AIMS: Polymorphisms in cell cycle genes are considered prognostic as radiosensitivity markers in patients with head and neck squamous cell carcinoma. Therefore, we aimed to investigate the relationship of ATM 5557G>A, ATM IVS62 + 60G>A, TP53 215G>C, BCL2-938C>A, TGFß-509C>T, and TGFß 29C>T with radiotherapy response. MATERIALS AND METHODS: Genotyping was performed by polymerase chain reaction followed by restriction fragment length polymorphism in 210 patients with oral cavity/oropharyngeal carcinoma and 101 patients with laryngeal tumors. RESULTS: In irradiated oral cavity/oropharyngeal tumors, the ATM IVS62 + 60G>A AA genotype significantly increased local recurrence risk (odds ratio [OR] = 4.43; confidence interval [CI] = 1.22-16.13) and the BCL2-938C>A C allele and the TGFß-509C>T T allele were associated with worse disease-specific survival (hazard ratio [HR] = 0.46; CI = 0.24-0.90 and HR = 2.20; CI = 1.12-4.29, respectively). In irradiated laryngeal carcinoma, the TGFß 29C>T C allele was associated with increased local recurrence risk (OR = 0.09; CI = 0.02-0.53), death rate (OR = 0.18; CI = 0.04-0.86), and worse local disease-free and disease-specific survival rates (HR = 0.13; CI = 0.03-0.59 and HR = 0.21; CI = 0.07-0.60, respectively), while the BCL2-938C>A C allele was related to a worse disease-specific survival (HR = 0.32; CI = 0.12-0.83). DISCUSSION: These results can help individualize treatment according to a patient's genetic markers. We demonstrated that ATM IVS62 + 60G>A, TGFß 29C>T, TGFß-509C>T, and BCL2-938C>A can function as biomarkers of tumor radiosensitivity, being candidates for a predictive genetic profile of radiotherapy response.