Epigenetic mechanisms of particulate matter exposure: air pollution and hazards on human health.

Environmental pollution nowadays has not only a direct correlation with human health changes but a direct social impact. Epidemiological studies have evidenced the increased damage to human health on a daily basis because of damage to the ecological niche. Rapid urban growth and industrialized societies importantly compromise air quality, which can be assessed by a notable accumulation of air pollutants in both the gas and the particle phases. Of them, particulate matter (PM) represents a highly complex mixture of organic and inorganic compounds of the most variable size, composition, and origin. PM being one of the most complex environmental pollutants, its accumulation also varies in a temporal and spatial manner, which challenges current analytical techniques used to investigate PM interactions. Nevertheless, the characterization of the chemical composition of PM is a reliable indicator of the composition of the atmosphere, the quality of breathed air in urbanized societies, industrial zones and consequently gives support for pertinent measures to avoid serious health damage. Epigenomic damage is one of the most promising biological mechanisms of air pollution-derived carcinogenesis. Therefore, this review aims to highlight the implication of PM exposure in diverse molecular mechanisms driving human diseases by altered epigenetic regulation. The presented findings in the context of pan-organic cancer, fibrosis, neurodegeneration and metabolic diseases may provide valuable insights into the toxicity effects of PM components at the epigenomic level and may serve as biomarkers of early detection for novel targeted therapies.

Intrinsic innervation of the ovary and its variations in the rat senescence process.

Ovarian functions decrease with perimenopause. The ovary has extrinsic innervation, but the neural influence on ovarian functions and dysfunction is not well-studied. The present study aimed to biochemically and morphometrically characterize the intrinsic neurons in ovaries from young adult, middle-aged, and senescent Long Evans CII-ZV rats (3, 12, and 15 months old, respectively). Ovaries were extracted from four rats of each age group (n = 12 total), cryopreserved, and processed for immunofluorescence studies with the primary NeuN/ß-tubulin and NeuN/tyrosine hydroxylase (TH) antibodies. The soma area and number of intrinsic neurons in the ovarian stroma, surrounding follicles, corpus luteum, or cyst were evaluated. The intrinsic neurons were grouped in cluster-like shapes in ovarian structures. In senescent rats, the intrinsic neurons were mainly localized in the ovarian stroma and around the cysts. The number of neurons was lower in senescent rats than in young adult rats (p < 0.05), but the soma size was larger than in young adult rats. Immunoreactivity to TH indicated the presence of noradrenergic neurons in the ovary with the same characteristics as NeuN/ß-tubulin, which indicates that they are part of the same neuronal group. Taken together, the findings indicate that the intrinsic neurons may be related to the loss of ovarian functions associated with aging.

Sodium metavanadate treatment improves glycogen levels in multiple tissues in a model of metabolic syndrome caused by chronic cadmium exposure in Wistar rats.

Cadmium, one of the more hazardous environmental contaminants, has been proposed as a metabolic disruptor. Vanadium has emerged as a possible treatment for metabolic diseases. Both metals are important in public health. We aimed to investigate whether vanadium treatment is effective against metabolic disturbances caused by chronic exposure to the lowest-observable adverse effect level of cadmium. Male Wistar rats were exposed to cadmium (32.5 ppm) in drinking water for 3 months. Metabolic complications such as overweight, visceral adipose gain, hyperglycemia, impaired glucose tolerance, and dyslipidemia were detected, and low glycogen levels and steatosis were observed in the tissues. Then, the control and treated animals were subdivided and treated with a solution of 5 µM NaVO3/kg/twice a week for 2 months. The control-NaVO3 group did not show zoometric or metabolic changes. A strong interaction of NaVO3 treatment over cadmium metabolic disruption was observed. The vanadium accumulation diminished cadmium concentration in tissues. Also, vanadium interaction improved glucose homeostasis. The major effect was observed on glycogen synthesis, which was fully recovered in all tissues analyzed. Additionally, vanadium treatment prevented overweight and visceral fat accumulation, improving BMI and the percentage of fat. However, NaVO3 treatment did not have an effect on dyslipidemia or steatosis. In conclusion, this work shows that vanadium administration has a strong effect against metabolic disturbances caused by chronic cadmium exposure, observing powerful interaction on glucose homeostasis.

In Adult Rats With Polycystic Ovarian Syndrome, Unilateral or Bilateral Vagotomy Modifies the Noradrenergic Concentration in the Ovaries and the Celiac Superior Mesenteric Ganglia in Different Ways.

In rats with polycystic ovarian syndrome (PCOS) induced by estradiol valerate (EV) injection, sectioning of the vagus nerve in the juvenile stage restores ovulatory function, suggesting that the vagus nerve stimulates the onset and development of PCOS. We analyzed whether in adult rats, the role played by the vagus nerve in PCOS development is associated with the nerve's regulation of noradrenergic activity in the celiac superior mesenteric ganglion (CSMG). Ten-day-old rats were injected with corn oil [vehicle (Vh)] or EV (2 mg). At 76 days of age, rats injected with Vh or EV were subjected to sham surgery or the sectioning of one or both vagus nerves (vagotomy). The animals were sacrificed at 80-82 days of age at vaginal estrus smear. Compared to Vh-treated animals, EV-induced PCOS rats showed a lack of ovulation, the presence of follicular cysts, and a high concentration of testosterone, without changes in noradrenaline concentrations in the CSMG or ovaries. In PCOS rats, sham surgery lowered serum testosterone and noradrenaline concentrations in the CSMG but did not restore ovulation. In animals with PCOS, vagotomy lowered testosterone concentrations to a larger degree than in sham-surgery animals. The ovaries of rats with PCOS and vagotomy showed fresh corpora lutea, indicating ovulation. In EV-treated rats with unilateral vagotomy, the concentration of noradrenaline in the CSMG was similar to that in rats with PCOS and sham surgery, which did not ovulate, while in the ovaries of PCOS rats with left or bilateral vagotomy, the noradrenaline concentration was lower than that in sham-surgery-treated animals. Our results suggest that the vagus nerve regulates PCOS development through a different mechanism than the increase in the noradrenergic activity in the CSMG; however, in ovaries, the restoration of ovulation is associated with a decrease in ovarian noradrenaline.

In rats with estradiol valerate-induced polycystic ovary syndrome, the acute blockade of ovarian ß-adrenoreceptors improve ovulation.

BACKGROUND: Polycystic ovary syndrome is characterized by hyperactivity of the ovarian sympathetic nervous system, increases in the content and release of norepinephrine, as well as decreases in the number of ß-adrenoreceptors. In the present study, ß-adrenoreceptors in the ovaries of rats with polycystic ovary syndrome were blocked and analyzed the resultant effects on ovulation, hormone secretion and the enzymes responsible for the synthesis of catecholamines. METHODS: At 60 days of age, vehicle or estradiol valerate-treated rats were injected with propranolol [10- 4 M] into the ovarian bursas on oestrus day. The animals were sacrificed on the next day of oestrus, and the ovulation response, the steroid hormone levels in the serum and the immunoreactivity of tyrosine hydroxylase and dopamine ß-hydroxylase in the ovaries were measured. RESULTS: In animals with the induction of polycystic ovary syndrome and ß-adrenoreceptor blocking, ovulation was restored in more than half of the animals and resulted in decreased hyperandrogenism with respect to the levels observed in the estradiol valerate-treated group. Tyrosine hydroxylase and dopamine ß-hydroxylase were present in the theca cells of the growing follicles and the interstitial gland. Injection of propranolol restored the tyrosine hydroxylase and ovarian dopamine ß-hydroxylase levels in rats with polycystic ovary syndrome induction. CONCLUSIONS: The results suggest that a single injection into the ovarian bursas of propranolol, a nonselective antagonist of ß-adrenoreceptor receptors, decreases the serum testosterone concentration and the formation of ovarian cysts, improving the ovulation rate that accompanies lower levels of tyrosine hydroxylase and dopamine ß-hydroxylase in the ovary.

Both the Suprachiasmatic Nucleus and the Superior Ovarian Nerve Contribute to the Processes of Ovulation and Steroid Hormone Secretion on Proestrus.

The aims of the present study were to analyze if the superior ovarian nerve (SON) plays a role in the neural signals from suprachiasmatic nucleus (SCN) that lead to ovulation and ovarian steroids secretion on proestrus day. Rats on proestrus day were treated at 11.00 to 11.30 or 17.00 to 17.30 hours with 1 of the 3 experimental procedures (1) unilateral or bilateral SON sectioning, (2) unilateral or bilateral injury to the SCN, or (3) unilateral injury to the SCN followed by unilateral sectioning of the SON ipsilateral to the treated SCN. Treatments were evaluated 24 hours after surgical procedures. Compared to laparotomized animals, right or bilateral SON sectioning treatment at 17.00 hours resulted in lower ovulation rates and number of ova shed by the right ovary. The ovaries of nonovulating animals showed early follicular luteinization signs and trapped ova. Bilateral SCN injury treatment at 11.00 hours resulted in anovulation; whereas right SCN injury treatment, with or without right SON sectioning, resulted in a lower number of ova shed. Injecting luteinizing hormone-releasing hormone to animals with bilateral SCN injury restored ovulation. In rats with unilateral or bilateral SON sectioning, or with injury to the SCN with or without unilateral sectioning of the SON, the effects on hormone levels depended of the hormone studied and the time of day treatment was performed. The present results suggest that on proestrus day, the role of the right or both SON in ovulation and steroid hormone secretion regulation takes place through different neuroendocrine mechanisms from SCN.

Caracterización clínica y epidemiológica de fiebre chikungunya en México / Clinical and epidemiological characterization of chikungunya fever in Mexico

RESUMEN El 6 de diciembre de 2013, la Organización Panamericana de la Salud (OPS) y la Organización Mundial de la Salud (OMS) notificaron la confirmación de los dos primeros casos de transmisión autóctona en la Región de las Américas de fiebre chikungunya (CHIK) en la isla de Saint Martin (Antillas Neerlandesas). Para el período 2013-2014, el total de casos confirmados fue de 25 627 distribuidos en 43 países, donde México reportó 155 casos en cinco estados. La información de los casos de CHIK en México se obtuvo de la base de datos de la Dirección General de Epidemiología, dependiente de la Secretaría de Salud de México. La distribución por sexo de los casos autóctonos confirmados de CHIK para el año 2015 indica 64% para el sexo femenino (5 583) y 36% para el sexo masculino (3 085). Los síntomas más frecuentes fueron: fiebre en 98% de los casos (8 564), seguido por cefalea con 91,6% (7 941), mialgias en 89,9% (7 792), artralgias leves en 73,5% (6 367), poliartralgias graves en 72,6% (6 295) y exantema en 58% (5 032). La presentación clínica de los casos autóctonos de CHIK en México ha mostrado algunas características clínicas diferentes de las que se han observado en los brotes de los países africanos, asiáticos y otras regiones de América, como por ejemplo un mayor porcentaje de casos con cefalea y mialgias y un menor porcentaje de casos con artralgias.(AU)

ABSTRACT On 6 December 2013, the Pan American Health Organization (PAHO) and the World Health Organization (WHO) reported confirmation of the first two cases of indigenous transmission of chikungunya fever (CHIK) in the Region of the Americas on the island of Sint Maarten (Netherlands Antilles). For the period 2013-2014, a total of 25 627 confirmed autochthonous cases were distributed in 43 countries, with Mexico reporting 155 cases in five states. Information on cases of CHIK in Mexico was obtained from the database of the General Directorate of Epidemiology (Ministry of Health of Mexico). The distribution of confirmed autochthonous cases of CHIK for 2015, by sex, was 64% female (5 583) and 36% male (3 085). The most frequent symptoms were fever in 98% of cases (8 564), followed by headache in 91.6% (7 941), myalgia in 89.9% (7 792), mild arthralgias in 73.5% (6 367), severe polyarthralgia in 72.6% (6 295), and exanthema in 58% (5 032). The clinical presentation of autochthonous cases of CHIK in Mexico has shown several clinical manifestations different from those seen in outbreaks in African and Asian countries and other regions in the Americas; for example, a greater percentage of cases with headache and myalgia and a smaller percentage of cases with arthralgia.(AU)

Effects of ovarian dopaminergic receptors on ovulation.

Hormonal and neural signals regulate the ovarian follicular development. The present study's hypothesis is that the blockade of ovarian dopamine receptors locally will affect follicle development and ovulation. Groups of adult 4-day cyclic rats of the CII-ZV strain on estrus, diestrus-1, diestrus-2, or proestrus day were injected with vehicle, haloperidol (DA2 > DA1 blocker), sulpiride (DA2 blocker), or SCH-23390 (DA1 blocker) into the bursa of both ovaries at 08:00, 13:00, or 20:00 h. Animals were sacrificed the following predicted estrus day. The following treatments blocked ovulation: injecting haloperidol to rats on estrus or diestrus-1 at 8:00, 13:00, or 20:00 h and to rats on diestrus-2 at 08:00, or 20:00 h; injecting SCH-23390 to rats on diestrus-1 at 8:00, 13:00, or 20:00 h; injecting sulpiride to rats on estrus at 20:00 h, diestrus-1 at 08:00, 13:00, or 20:00 h and to rats on diestrus-2 at 08:00 h. In rats treated with any of the dopamine antagonists that blocked ovulation, injecting GnRH at 14.00 h on the next predicted proestrus day restored ovulation. Injecting estradiol benzoate at 14.00 h of the next predicted diestrus-2 restored ovulation in some animals treated with haloperidol on estrus or diestrus-2 and was ineffective in rats treated on diestrus-1. In rats treated with sulpiride or SCH-23390 ovulation occurred in most animals (SCH-23390: 6/8; SPD: 9/12). Present results suggest that dopamine ovarian receptors' participation in regulating follicular development and ovulation varies along the estrus cycle, with their most prominent activity occurring on diestrus-1.

Lack of sensorial innervation in the newborn female rats affects the activity of hypothalamic monoaminergic system and steroid hormone secretion during puberty.

There is evidence that sensory innervation plays a role regulating ovarian functions, including fertility.Since sensory denervation by means of capsaicin in newborn female rats results in a lower response togonadotropins, the present study analyzed the effects that sensory denervation by means of capsaicin in neonatal rats has on the concentration of monoamines in the anterior(AH) and medium (MH) hypothalamus, and on steroid hormone levels in serum. Groups of newborn female rats were injected subcutaneously with capsaicin and killed at 10, 20, and 30 days of age and on the first vaginal estrous.The concentrations of noradrenaline, dopamine, serotonin(5-HT), and their metabolites in the AH and MH were measured using HPLC, and the levels of estradiol (E),progesterone (P), testosterone (T), FSH, and luteinizing hormone using radioimmunoanalysis. The results show thatat 20 days of age, capsaicin-treated rats have lowernoradrenergic and serotonergic activities in the AH, and that the dopaminergic activity was lower in the MH. These results suggest that the sensorial system connections within the monoaminergic systems of the AH and MH are different.Capsaicin-treated animals had lower T, E, and P levels than in the control group, suggesting that the lower activity in the AH monoaminergic system and lower hormonesecretion could be explained by the blockade of information mediated by the sensory innervation (probably substance P), mainly between the ovary and the AH.

Unilateral or bilateral vagotomy induces ovulation in both ovaries of rats with polycystic ovarian syndrome.

BACKGROUND: Injecting estradiol valerate (EV) to pre-pubertal or adult female rat results in effects similar to those observed in women with polycystic ovarian syndrome (PCOS). One of the mechanisms involved in PCOS development is the hyperactivity of the sympathetic nervous system. In EV-induced PCOS rats, the unilateral sectioning of the superior ovarian nerve (SON) restores ovulation of the innervated ovary. This suggests that, in addition to the sympathetic innervation, other neural mechanisms are involved in the development/maintenance of PCOS. The aims of present study were analyze if the vagus nerve is one of the neural pathways participating in PCOS development. METHODS: Ten-day old rats were injected with EV dissolved in corn oil. At 24-days of age sham-surgery, unilateral, or bilateral sectioning of the vagus nerve (vagotomy) was performed on these rats. The animals were sacrificed at 90-92 days of age, when they presented vaginal estrous preceded by a pro-estrus smear. RESULTS: In EV-induced PCOS rats, unilateral or bilateral vagotomy restored ovulation in both ovaries. Follicle-stimulating hormone (FSH) levels in PCOS rats with unilateral or bilateral vagotomy were lower than in control rats. CONCLUSIONS: This result suggests that in EV-induced PCOS rats the vagus nerve is a neural pathway participating in maintaining PCOS. The vagus nerve innervates the ovaries directly and indirectly through its synapsis in the celiac-superior-mesenteric ganglion, where the somas of neurons originating in the SON are located. Then, it is possible that vagotomy effects in EV-induced PCOS rats may be explained as a lack of communication between the central nervous system and the ovaries.

Unilateral sectioning of the superior ovarian nerve of rats with polycystic ovarian syndrome restores ovulation in the innervated ovary.

The present study tested the hypothesis that if polycystic ovary syndrome (PCOS) results from activating the noradrenergic outflow to the ovary, unilaterally sectioning the superior ovarian nerve (SON) will result in ovulation by the denervated ovary, and the restoration of progesterone (P4), testosterone (T) and estradiol (E2) normal serum level. A single 2 mg dose of estradiol valerate (EV) to adult rats results in the development of a syndrome similar to the human PCOS. Ten-day old rats were injected with EV or vehicle solution (Vh) and were submitted to sham surgery, unilateral or bilateral sectioning of the SON at 24-days of age. The animals were sacrificed at 90 to 92 days of age, when they presented vaginal estrus preceded by a pro-estrus smear. In EV-treated animals, unilateral sectioning of the SON restored ovulation by the innervated ovary and unilateral or bilateral sectioning of the SON normalized testosterone and estradiol levels. These results suggest that aside from an increase in ovarian noradrenergic tone in the ovaries, in the pathogenesis of the PCOS participate other neural influences arriving to the ovaries via the SON, regulating spontaneous ovulation. Changes in P4, T and E2 serum levels induced by EV treatment seem to be controlled by neural signals arising from the abdominal wall and other signals arriving to the ovaries through the SON, and presents asymmetry.