Aleksandra Rutkowska

Bisphenol A (BPA) and its potential role in the pathogenesis of the polycystic ovary syndrome (PCOS).

Abstract Polycystic ovary syndrome (PCOS) is the most common and the most heterogeneous endocrine disorder in premenopausal women. Apart from signs of hyperandrogenism such as acne, hirsutism and hair loss, women with PCOS usually present with menstrual irregularities and fertility problems.Additionally, they are often characterized by impaired glucose tolerance, which usually leads to the development of type 2 diabetes mellitus (T2DM). This review article describes current and novel approach to the pathomechanisms of PCOS and the potential role of an endocrine disrupting chemical (“endocrine disruptor” – ED) – bisphenol A (BPA), which is commonly used as a plasticizer and due to its molecular structure can interact with estrogen receptors (ERs). Recent observations point to the higher levels of BPA in biological fluids of women with PCOS and its role in the pathogenesis of hyperandrogenism and hyperinsulinemia. It seems that mother’s exposure to BPA during pregnancy may also lead to the development of PCOS in the female offspring.

Inflammatory response of coronary artery disease postmenopausal women is associated with the IVS1-397T > C estrogen receptor α polymorphism

We analyzed the relationship between the IVS1-397T > C polymorphism of estrogen receptor alpha gene and inflammatory response of eighty postmenopausal women with an established coronary artery disease (CAD). We found that the IVS1-397T allele carriers exhibited an enhanced inflammatory response in vivo and in vitro. These patients had a higher number of total monocytes and their CD14(+)CD16(+) inflammatory subset in relation to CC homozygotes. The CT and TT womens LPS-stimulated whole blood cell cultures produced more IL6 and TNFalpha than did the cultures of CC women. Moreover, significantly more of the T allele patients had major post-coronary artery bypass grafting complications and less of them experienced subjective angina pectoris improvement. Summarizing, the IVS1-397T > C polymorphism allows us to identify a group of postmenopausal women with the strong inflammatory response which is associated with a higher incidence of the major post-CABG adverse cardiovascular complications.

Polish Society of Endocrinology Position statement on endocrine disrupting chemicals (EDCs).

With the reference to the position statements of the Endocrine Society, the Paediatric Endocrine Society, and the European Society of Paediatric Endocrinology, the Polish Society of Endocrinology points out the adverse health effects caused by endocrine disrupting chemicals (EDCs) commonly used in daily life as components of plastics, food containers, pharmaceuticals, and cosmetics. The statement is based on the alarming data about the increase of the prevalence of many endocrine disorders such as: cryptorchidism, precocious puberty in girls and boys, and hormone-dependent cancers (endometrium, breast, prostate). In our opinion, it is of human benefit to conduct epidemiological studies that will enable the estimation of the risk factors of exposure to EDCs and the probability of endocrine disorders. Increasing consumerism and the industrial boom has led to severe pollution of the environment with a corresponding negative impact on human health; thus, there is great necessity for the biomonitoring of EDCs in Poland.

Endocrine disrupting chemicals as potential risk factor for estrogen-dependent cancers.

Civilization, industrialization, and urbanization create an environment where humans are continuously exposed to endocrine disrupting chemicals (EDCs). Some of breast cancers and endometrial cancer, which are the most common female malignant neoplasms, are estrogen-dependent tumors. Prolonged exposure to estrogens or substances with estrogenic properties may be a risk factor for their development. This paper aimed to discuss the potential adverse effect of EDCs on human health, including the role of EDCs in hormone-dependent carcinogenesis. A review of literature regarding the sources of environmental exposure to EDCs and molecular mechanisms of their action was performed. We analyzed the possible mechanisms of how these substances alter the function of the endocrine system, resulting in adverse health effects. Hundreds of substances with endocrine disrupting potential have been identified in our environment. There is accumulating evidence linking exposure to EDCs with the development of mammary and endometrial cancer. By interacting with steroid receptors, EDCs can impact the cellular processes potentially leading to carcinogenesis. There are also data showing the effect of EDCs on immune dysfunction. During lifespan, people are usually exposed to a mixture of various EDCs, which complicates the assessment of individual substances or compounds implicated in cancer development. As the prevalence of hormone-dependent tumors among women continues to increase, their successful prevention is of human benefit. Institutions representing medicine, science, industry, and governments should develop joint strategies to decrease exposure to EDC, and thus to reduce the risk of hormonedependent tumors in women.

Evaluation of peripheral blood T lymphocyte surface activation markers and transcription factors in patients with early stage non-small cell lung cancer

Lung cancer cells harboring multiple mutations as a consequence of long-term damage by different etiologic factors are responsible for high immunogenicity. Immune checkpoint inhibitors significantly improve treatment results in non-small cell lung cancer (NSCLC). Unfortunately, the role of T-lymphocytes in early NSCLC has not been sufficiently elucidated. The aim of this study was to characterize peripheral blood T cells expressing several selected surface antigens (CD4, CD8, CD25, CD28, PD-1, CTLA-4) and transcription factors (T-bet, ROR-yt, Fox-P3, GATA-3) in this patient population. The study group (LC) consisted of 80 treatment-naïve patients with T1/2aN0M0 NSCLC and was compared with 40 cancer-free patients matched for non-oncological diseases and demographic parameters (CG). Significantly higher counts of CTLA-4+cells (in both CD4+and CD8+subtypes), a lower proportion of PD-1 expressing cells and a significantly higher percentage of Fox-P3+CD4+cells were found in the LC group. The high proportion of CD4+PD-1+cells significantly correlated with poor outcomes in LC group, while low CD4/CD8 ratio predicted a better prognosis. Based on our results it seems that NSCLC even at early stages of development initiate changes in the proportions of T cells that may have a significant impact on the clinical outcome.

Do Advanced Glycation End Products (AGEs) Contribute to the Comorbidities of Polycystic Ovary Syndrome (PCOS)

Advanced glycation end products (AGEs) are formed both during the endogenous and exogenous reactions and are implicated in the process of ageing, pathogenesis of diabetes, atherosclerosis, female fertility, and cancers. Food and smoking are the most important sources of exogenous AGEs in daily life. The biochemical composition of meal, cooking methods, time and temperature of food preparation may impact AGEs formation, therefore Western-type diet, rich in animal-derived products as well as in fast foods seems to be the main source of AGEs. Both, endogenous and exogenous AGEs can act intracellularly or during serum interaction with cell surface receptors called RAGE influencing variety of molecular pathways. Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age. The aetiology of this disorder remains unclear, however the environmental and genetic factors may play an important role in its pathogenesis. Nevertheless, PCOS women have increased factors for reproductive and cardiometabolic comorbidities. AGEs can contribute to the pathogenesis of PCOS as well as its consequences. It has been shown that chronic inflammation and increased oxidative stress may be a link between the mechanisms of AGEs action and the metabolic and reproductive consequences of PCOS. This review highlights that high dietary AGEs intake promotes deteriorating biological effects in women with PCOS, whereas AGEs restriction seems to have beneficial impact on women health. Better understanding AGEs formation and biochemistry as well as AGE-mediated pathophysiological mechanisms may open new therapeutic avenues converging to the achievement of the complete treatment of PCOS and its consequences.

Determination of trace levels of eleven bisphenol A analogues in human blood serum by high performance liquid chromatography–tandem mass spectrometry

Chemicals showing structural or functional similarity to bisphenol A (BPA), commonly called BPA analogues, have recently drawn scientific attention due to their common industrial and commercial application as a substitute for BPA. In the European Union, the use of BPA has been severely restricted by law due to its endocrine disrupting properties. Unfortunately, it seems that all BPA analogues show comparable biological activity, including hormonal disruption, toxicity and genotoxicity. Until now, the knowledge about human exposure to BPA analogues is scarce, mainly due to the lack of the data concerning their occurrence in human derived biological samples. This study presents the development of an analytical method for determination of trace levels of eleven BPA analogues in human blood serum samples. The method involves fast and simple liquid-liquid extraction, using low sample and solvent volumes. Chromatographic separation of analytes was optimized using one-factor-at-a-time approach (mobile phase composition, gradient shape, chromatographic column selection, separation temperature, etc.). The method allows for effective separation of the analytes, even in the case of configurational isomers (bisphenol M and bisphenol P). The calibration curves for all analytes were linear in the range tested. The limits of detection and quantitation were in the range of 0.0079÷0.039ng/mL and 0.024÷0.12ng/mL respectively. Compound-dependent recovery values were in the rage of 88÷138%. Matrix effects were mitigated with the help of matrix-matched calibration curves prepared for every batch of samples. Results obtained after the analysis of 245 real human blood serum samples indicate that human beings are exposed to different BPA analogues, that are present in the environment and in common, daily use products.

Daily diet containing canned products significantly increases serum concentrations of endocrine disruptor bisphenol A in young women

Nowadays, exposure to environmental factors is considered to be one of the possible causes of several lifestyle diseases, such as obesity, type 2 diabetes, cardiovascular disease, and cancer. Particularly noteworthy are endocrine‑disrupting chemicals (EDCs), which affect the metabolism of hormones and interact with their receptors, thus exerting adverse health effects. One of the most ubiquitous EDC in daily life is bisphenol A (BPA), an organic compound that, due to its phenolic structure, has an ability to interact with estrogen receptors and is a weak environmental estrogen. BPA is a precursor of polycarbonates used in everyday objects, such as food packaging, plastic bottles, toys, dental sealants and composites, thermal paper, and electronic and medical devices. It is also a component of polyvinyl chloride and epoxy resins used as the inner layer of food cans, hence BPA is detected in a variety of canned products. Diet is the crucial source of human exposure to this EDC. Its concentrations in alimentary products correspond with the duration of storage as well as the temperatures used during sterilization, pasteurization, or heating directly before consumption. Moreover, BPA may migrate to the content of a can as a consequence of mechanical factors such as denting and reshaping of cans. The presence of BPA has been shown in various human tissues and fluids, such as the adipose tissue, placenta, breast milk, urine, serum, and saliva. A number of studies emphasized its potential role in the pathogenesis of several endocrinopathies and fertility problems. High serum BPA concentrations were also associated with obesity, type 2 diabetes, cardiovascular disease, and hormone‑dependent neoplasms (ie, breast or prostate cancer). According to the European Food Safety Authority, high BPA exposure in women is 1.063 µg/kg of body weight per day (bw/d) (0.388 µg from dietary and 0.675 µg from nondietary sources), whereas an average exposure is 0.216 µg/kg of bw/d (0.132 µg and 0.084 µg, respectively). Only recently, the European Food Safety Authority has reduced the toxicological reference values and established a temporary tolerable daily intake of 4 µg/kg of bw/d, which is far lower than the previous tolerable daily intake (50 µg/kg of bw/d). The aim of this study was to evaluate serum BPA concentrations in young women after 7 days of dietary exposure to canned products that are a source of this EDC in daily life.