Today, in many countries of the world, including Iran, air pollution has become one of the major human problems, which experts have attributed to the excessive increase in industrial and human activities, consumption of fossil fuels, and population density. Pollution is tiny particles that include heavy metals and carbon compounds. These particles play a significant role in reducing the health level of people living in big cities and industrial centers. The relationship between these pollutions and the increased incidence of cancers, respiratory disorders, heart failure, and digestive problems has been reported in many studies.
PM2.5 with an aerodynamic diameter of fewer than 2.5 micrometers, which are suspended for a long time and travel long distances in both open spaces. Indoor PM2.5 atmospheres and the toxic compounds attached may cause a wide range of disorders. Due to the lifestyle of people these days, air pollution in the form of suspended particles PM2.5 is known to be the biggest threat to environmental health. In addition to affecting the biological pathways of the respiratory organs, air pollution containing PM2.5 has very dangerous effects during pregnancy and the female reproductive system because these particles can enter the bloodstream through the respiratory system and even during pregnancy and deliver to the fetus.
Therefore, it is very important to know the precise and effective mechanisms of pollutant particles and their functional pathways on the tissue structures of the reproductive system to find an effective prevention or treatment method for these injuries, measuring hormonal changes that are an indicator in determining cancers, including cancer. The uterus is considered. These particles contain metals, heavy metals, and polycyclic aromatic hydrocarbons, and they can penetrate the tissues of mammals, including humans, and are considered a threat to human health. After these particles enter the body, reactive oxygen species appear in the body, which causes the phenomenon of oxidative stress cause inflammatory reactions. Secondary pollutants are formed from the chemical reactions of primary pollutants in the atmosphere and usually include natural compounds of the environment such as water and oxygen. Major secondary pollutants include ozone, nitrogen oxides, and fine secondary particles. An estrogen is a group of the most important female sex hormones in the ovaries. Estrogen is released from the egg in the follicular phase of the normal ovarian cycle. By binding to the estrogen receptor in the cytoplasm, estrogen increases the production of DNA, RNA, and other proteins in the target tissue. Estrogen in the uterine wall causes the growth and hyperemia of the endometrium. Also, in the hypothalamus, the release of gonad stimulating hormone decreases under the influence of estrogen, and in the pituitary gland, the release of FSH and LH reduces. Steroid hormone receptors are intracellular proteins that bind to DNA and play the role of cell growth and development regulators. The binding of the hormone leads to the change of the receptor's shape; after that, the binding of the receptor-hormone complex to the nucleus occurs. In the core of this complex, it is connected to certain sequences of nucleotides, which leads to the regulation of the transcription of the target genes, and the presence of the estrogen receptor gene does not mean that all cells express it.
As a result of binding to estrogen, this receptor is activated. A number of its target genes related to cell division are expressed, i.e., they act as a transcription factor, so all these receptors are not expressed because cell division increases strongly. And only a part of them is expressed that can respond to estrogen. These genes include cytokine-related genes, adhesion molecules, growth factors, degrading enzymes, and extracellular matrix components. Progesterone is secreted from the corpus luteum during the normal ovulation cycle. This hormone is also released during pregnancy. The progesterone receptor activates its target genes by binding with the hormone as a transcription factor. This receptor is an intracellular receptor that is activated by the steroid hormone progesterone. This protein receptor in humans is encoded by the PGR gene located on the long arm of chromosome 44. Estrogen and progesterone receptors are sensitive to proteolytic enzymes and heat. Research has shown that there is a kind of dependence between the estrogen receptor and the progesterone receptor in the cell, so that in the absence of estrogen, an increase in the number of estrogen receptors and a decrease in the number of progesterone receptors can be expected, or vice versa, and perhaps the amount of hormones in the tissue affect the expressed receptors.
There is a significant relationship between the presence of estrogen and progesterone receptors and some types of tumors, which helps to diagnose and treat these types of tumors. The more differentiated the cancer is, the more receptors it has. Determining the cell concentrations of estrogen receptor and progesterone receptor in cancer are used to determine those patients who benefit from hormone therapy. Also, estrogen and progesterone receptors are very effective in determining the type of treatment; for example, it has been observed that tamoxifen increases the effect of chemotherapy drugs before menopause by inhibiting estrogen receptors. Considering that it is important to know the precise and effective mechanism of polluting particles on the tissue structure of the ovary and uterus to be able to find an effective prevention or treatment method for injuries, as well as measure changes in estrogen receptors and progesterone receptors, which are indicators in determining cancers, including breast cancer and It is the womb. Therefore, in this study, the role of PM2.5 pollutants on changes in hormonal indices and histopathology of uterine tissue in rats was investigated over a period of three months, and the obtained results were analyzed.
The working method was after sampling and evaluating the concentration of PM2.5, heavy metals, and polycyclic hydrocarbons (PAHs) from 24 female Wistar rats aged four weeks. Average weight of 85 ± 10 grams from The Pasteur Institute of Iran was purchased and used. Animals were divided into three control groups receiving clean air with standard conditions (Healthy Control), receiving gaseous pollutants (Exposure1), and receiving PM2.5 plus gaseous pollutants (Exposure2) and in a period of a three-month treatment was evaluated to investigate the changes in hormonal indicators including LH, FSH, progesterone, and estrogen as well as histopathological changes of uterine tissue in exposed and control Wistar rats. The results of PM2.5 concentration analysis showed a high level of this pollutant along with heavy metals and PAHs. Hormonal findings showed that in the Exposure2 group compared to the Healthy Control, a statistically significant decrease in estrogen, FSH, progesterone, and a statistically significant increase in LH were observed. Also, compared to Exposure1, these changes in hormone levels were substantial. Histopathological studies of the uterine section showed endometrial degeneration in the Exposure1 group, the endometrial decline in Exposure2 group, infiltration of inflammatory cells in the endometrium, and atrophy of the glandular epithelium, and there were statistically significant changes in the comparison of the severity of these changes between the two treatment groups. Exposure of mice to PM2.5 for three months interfered with the level of expression of hormones involved in the fertility and reproduction system, leading to uterine damage, which results were confirmed by observing the histopathological findings. PM2.5 can significantly cause serious risks to women's reproductive system; therefore, applying serious laws regarding the control and solution of the air pollution problem in big cities requires management and executive urgency to solve this problem. The present study using animal modeling and hormonal and pathology examinations showed that PM2.5 is the most dangerous air pollution substance affecting hormonal pathways, genes, and oxidative stress of the female reproductive system, which may lead to problems. Reproduction and interference in the secretion of essential sex hormones and pregnancy. Meanwhile, global warming and the increase of polluting industries may increase the amount of air pollution, so it is necessary to revise public policies and government laws to reduce PM2.5.