It is currently apparent that the intentional release of compounds through agricultural, industrial, and municipal activities has influenced the health of wildlife and human populations. Scientists are invited to study disturbances in the normal function of the reproductive system of genetically modified populations. When referring to a population, they rather use the term control or reference; the reason is an enormous rate of information concerning the endocrine-altering potential of plasticizers and dyes, as well as the possible influences of pesticides and industrial compounds on various endocrine endpoints, particularly regarding the concentration of estrogens. Here in, we provide an overview on the impact of chemical substances on female human reproductive health.

Disruption in coordinated co-expression of clock genes, like Period genes mutations, is linked with the increased risk of lung, gastrointestinal, hematologic and gynecologic cancers. Several clock genes have been found to functionally interplay with regulators of the cell cycle. It is suggested that abnormal cell cycle function in cancer could also be a consequence of a disrupted biological clock. Chrono-disruption, being studied in different cancer entities, including the gynecologic cancer, could provide time set intervention in cancer therapeuticschronotherapy in a 24 h-period.

Chronic inflammation and obesity are reciprocal pathophysiological processes underlying the element of the immune response. In obesity, alterations of cytokines are thought to contribute to a low grade inflammation within the adipose tissue affecting the development of several secondary diseases. Although micro-inflammation is involved in the initiation of immune response, excessive inflammation may promote tumor development. This review will discuss the reflexive relationship between endometrial cancer and obesity through immunomodulatory effects exerted by environmental chemicals.

In mammals, the components of the biological clock function peripherally in a complex network and modulate the transcription of specific target genes and their products, expressed rhythmically in a 24 h rhythm. The central biological clock includes the suprachiasmatic nucleus, which rhythmically 'tunes' peripheral clocks (Figure 1) [1][2][3][4][5][6][7][8].Having the molecular basis of SCN being clarified the so-called core clock genes such as per1-2, cry1-2, bmal1 [9,10] and the demonstration that these genes are rhythmically expressed in peripheral tissues, including the liver, adrenal and pituitary glands [11][12][13], this central clock model is reshaped [14][15][16].Clock/Bmal, formed by the product of the genes circadian locomotor output cycles kaput [Clock] and brain and muscle aryl hydrocarbon receptor nuclear translocator like-Arntl (Bmal) represents the transcription initiator of the feedback loops [17].Clock/Bmal binds to E-box in the promoter regions of target genes Period homolog 1, 2 and 3 genes (Per1, Per2, Per3), Cryptochrome genes (Cry1, Cry2), retinoic acid-related orphan receptor (Rora, Rorb, Rorc) and Rev-Erb nuclear orphan receptor(Rev-Erbα, RevErbβ) to activate their expression [18,19].Transcription of Pers and Crys is initiated during the day, while degradation during the night. PER and CRY proteins enter the nucleus, probably as a multimeric complex (PER/CRY), and inhibit Clock/Bmal-mediated transcription [20,21].As to the role of the PER/CRY complex, Cryptochrome (CRY) is a blue-light sensor, which regulates neuronal firing rate, that is AbstractThe creation of a biological clock adjusted to way of life synchronizers influences the function of peripheral clocks and by extension, all physiological processes as well as secretion of hormones. Further, disturbance of the function of the biological clock exerts a strong impact on the pathogenesis of several disorders, including diabetes mellitus, insomnia, depression, cardiovascular disease and cancer, linking the pathophysiology of many diseases to one molecular mechanism, the 'out of tune clock'.Keywords: Diabetes mellitus; Pathogenesis; Suprachiasmatic nucleus; Cryptochrome circadian entrainment in Drosophila melanogaster [22]. Light activates CRY. When CRY is activated TIM [timeless] degrades, tuning the clock daily. In the absence of cry, the clock can still be activated by light, though the mechanisms are unclear; possibly, there are two types of clock neurons having differential sensitivities to light and temperature [23].With regard to the remainder feedback loop, the ROR/Bmal/RevErb (RBR) frames the original shape [20]. ROR acts as an activator of Bmal and Rev-Erb as an inhibitor which results in tuning of Bmal transcription [24,25]. Suppression of Rev-Erbα expression resulted in elevated Clock mRNA expression consistent with RevErbα's role as a transcriptional repressor, adding a regulation role of the activity of the Bmal1/Clock heterodimer by regulation of the expression of both the Bmal1 and Clock genes directly (Figure 2) [26]...

Environmental chemicals that at certain doses interfere with the endocrine system are called endocrine disruptors; the disruption of homeostasis induced is including birth defects, feminizing effects and cancerous tumors. The critical window of development for most organisms is the in utero period where substantial damage to a developing fetus takes place after exposure to these chemicals; further, the risk of cancer development increases after environmental or occupational exposure later in life. In this review, epidemiological data are quoted regarding the increased cancer risk after the exposure to endocrine disruptors, while a current quantitation method of the chemical carcinogenesis evolving is also provided.