Total iodine quantification in fluids and tissues from iodine- or iodide-supplemented rats by ion chromatography following microwave-assisted digestion.

BACKGROUND: Iodine is a crucial component of thyroid hormones, and several reports have shown that iodine per se is implicated in the physiopathology of other organs. METHODS: Innovative ion chromatography detection following a four-step temperature ramp microwave digestion in 25-50 mM nitric acid was developed to measure total iodine in biological fluids and tissue samples from female Sprague-Dawley rats supplemented with 0.05% molecular iodine (I2) or 0.05% potassium iodide (I(-)) in drinking water. RESULTS: The reported method allows the measurement of total iodine with a limit of quantification of 13.7 µg L(-1), recoveries of 96.3-100.3%, and intra- and inter-assay variations, of 3.5% and 7.4% respectively. Analysis of biological fluids showed that after 48 hours, iodine-supplemented animals exhibited significantly higher levels of total iodine in both serum and urine compared with those supplemented with iodide. The half-life of iodine in serum and urine measured over the first 48 h showed similar patterns for both the I2 (7.89 and 7.76 hours) and I(-) (8.27 and 8.90 hours) supplements. Differential uptake patterns were observed in tissues after 6 days of supplements, with I(-) preferentially retained by thyroid, lactating mammary gland, and milk, and a slightly but significantly higher capture of I2 in pituitary, ovary, and virgin mammary gland. CONCLUSIONS: We developed a rapid, selective, and accurate digestion method to process fluid and tissue samples that permits reproducible measurements of total iodine by ion chromatography; iodine or iodide supplement show a similar serum and urine half-life, but organ-specific uptake depends on the chemical form of the iodine supplement.

Iodine uptake and prostate cancer in the TRAMP mouse model.

Iodine supplementation exerts antitumor effects in several types of cancer. Iodide (I⁻) and iodine (I2) reduce cell proliferation and induce apoptosis in human prostate cancer cells (LNCaP and DU-145). Both chemical species decrease tumor growth in athymic mice xenografted with DU-145 cells. The aim of this study was to analyze the uptake and effects of iodine in a preclinical model of prostate cancer (transgenic adenocarcinoma of the mouse prostate [TRAMP] mice/SV40-TAG antigens), which develops cancer by 12 wks of age. ¹²5I⁻ and ¹²5I2 uptake was analyzed in prostates from wild-type and TRAMP mice of 12 and 24 wks in the presence of perchlorate (inhibitor of the Na⁺/I⁻ symporter [NIS]). NIS expression was quantified by quantitative polymerase chain reaction (qPCR). Mice (6 wks old) were supplemented with 0.125 mg I⁻ plus 0.062 mg I2/mouse/day for 12 or 24 wks. The weight of the genitourinary tract (GUT), the number of acini with lesions, cell proliferation (levels of proliferating cell nuclear antigen [PCNA] by immunohistochemistry), p53 and p21 expression (by qPCR) and apoptosis (relative amount of nucleosomes by enzyme-linked immunosorbent assay) were evaluated. In both age-groups, normal and tumoral prostates take up both forms of iodine, but only I⁻ uptake was blocked by perchlorate. Iodine supplementation prevented the overexpression of NIS in the TRAMP mice, but had no effect on the GUT weight, cell phenotype, proliferation or apoptosis. In TRAMP mice, iodine increased p53 expression but had no effect on p21 (a p53-dependent gene). Our data corroborate NIS involvement in I⁻ uptake and support the notion that another transporter mediates I2 uptake. Iodine did not prevent cancer progression. This result could be explained by a strong inactivation of the p53 pathway by TAG antigens.

Iodine and doxorubicin, a good combination for mammary cancer treatment: antineoplastic adjuvancy, chemoresistance inhibition, and cardioprotection.

BACKGROUND: Although mammary cancer (MC) is the most common malignant neoplasia in women, the mortality for this cancer has decreased principally because of early detection and the use of neoadjuvant chemotherapy. Of several preparations that cause MC regression, doxorubicin (DOX) is the most active, first-line monotherapeutic. Nevertheless, its use is limited due to the rapid development of chemoresistance and to the cardiotoxicity caused by free radicals. In previous studies we have shown that supplementation with molecular iodine (I2) has a powerful antineoplastic effect in methylnitrosourea (MNU)-induced experimental models of MC. These studies also showed a consistent antioxidant effect of I2 in normal and tumoral tissues. METHODS: Here, we analyzed the effect of I2 in combination with DOX treatment in female Sprague Dawley rats with MNU-induced MC. In the first experiment (short) animals were treated with the therapeutic DOX dose (16 mg/kg) or with lower doses (8 and 4 mg/Kg), in each case with and without 0.05% I2 in drinking water. Iodine treatment began on day 0, a single dose of DOX was injected (ip) on day 2, and the analysis was carried out on day 7. In the second experiment (long) animals with and without iodine supplement were treated with one or two injections of 4 mg/kg DOX (on days 0 and 14) and were analyzed on day 56. RESULTS: At all DOX doses, the short I2 treatment induced adjuvant antineoplastic effects (decreased tumor size and proliferating cell nuclear antigen level) with significant protection against body weight loss and cardiotoxicity (creatine kinase MB, cardiac lipoperoxidation, and heart damage). With long-term I2, mammary tumor tissue became more sensitive to DOX, since a single injection of the lowest dose of DOX (4 mg/Kg) was enough to stop tumor progression and a second DOX4 injection on day 14 caused a significant and rapid decrease in tumor size, decreased the expression of chemoresistance markers (Bcl2 and survivin), and increased the expression of the apoptotic protein Bax and peroxisome proliferator-activated receptor type gamma. CONCLUSIONS: The DOX-I2 combination exerts antineoplastic, chemosensitivity, and cardioprotective effects and could be a promising strategy against breast cancer progression.

The extrathyronine actions of iodine as antioxidant, apoptotic, and differentiation factor in various tissues.

BACKGROUND: Seaweed is an important dietary component and a rich source of iodine in several chemical forms in Asian communities. Their high consumption of this element (25 times higher than in Western countries) has been associated with the low incidence of benign and cancerous breast and prostate disease in Japanese people. SUMMARY: We review evidence showing that, in addition to being a component of the thyroid hormone, iodine can be an antioxidant as well as an antiproliferative and differentiation agent that helps to maintain the integrity of several organs with the ability to take up iodine. In animal and human studies, molecular iodine (I2) supplementation exerts a suppressive effect on the development and size of both benign and cancerous neoplasias. Investigations by several groups have demonstrated that these effects can be mediated by a variety of mechanisms and pathways, including direct actions, in which the oxidized iodine dissipates the mitochondrial membrane potential, thereby triggering mitochondrion-mediated apoptosis, and indirect effects through iodolipid formation and the activation of peroxisome proliferator-activated receptors type gamma, which, in turn, trigger apoptotic or differentiation pathways. CONCLUSIONS: We propose that the International Council for the Control of Iodine Deficient Disorders recommend that iodine intake be increased to at least 3 mg/day of I2 in specific pathologies to obtain the potential extrathyroidal benefits described in the present review.

Uptake and antitumoral effects of iodine and 6-iodolactone in differentiated and undifferentiated human prostate cancer cell lines.

BACKGROUND: Evidence indicates that iodine per se could be implicated in the physiology of several organs that can internalize it. In thyroid and breast cancer, iodine treatments inhibit cell proliferation and induce apoptosis through a direct (mitochondria) and/or indirect effect (iodolipid generation). Here, we determined the uptake of iodide (I(-) ) and iodine (I(2) ), as well as the antiproliferative and apoptotic effects of 6-iodolactone (6-IL) and both forms of iodine in human prostate cells lines. METHODS: Non-cancerous (RWPE-1) and cancerous (LNCaP, DU-145) cells, as well as nude mice xenotransplanted with DU-145 cells were used as cancer models. Iodine uptake was analyzed with radioactive tracers, transporter expression by qRT-PCR, cell proliferation by blue trypan, apoptosis by enzyme immunoassay or fluorescence, BAX and BCL-2 by western-blot, and caspsase 3 by enzymatic assay. RESULTS: All three cell lines take up both forms of iodine. In RWPE-1 cells, I(-) uptake depends on the Na(+) /I(-) symporter (NIS), whereas it was independent of NIS in LNCaP and DU-145 cells. Antiproliferative effects of iodine and 6-IL were dose and time dependent; RWPE-1 was most sensitive to I(-) and 6-IL, whereas LNCaP was more sensitive to I(2) . In the three cell lines both forms of iodine activated the intrinsic apoptotic pathway (increasing the BAX/BCL-2 index and caspases). Iodine supplementation impaired growth of the DU-145 tumor in nude mice. CONCLUSION: Normal and cancerous prostate cells can take up iodine, and depending on the chemical form, it exerts antiproliferative and apoptotic effects both in vitro and in vivo.

Antineoplastic effect of iodine and iodide in dimethylbenz[a]anthracene-induced mammary tumors: association between lactoperoxidase and estrogen-adduct production.

Several groups, including ours, have reported that iodine exhibited antiproliferative and apoptotic effects in various cancer cells only if this element is supplemented as molecular iodine, or as iodide, to cells that are able to oxidize it with the enzyme thyroperoxidase. In this study, we analyzed the effect of various concentrations of iodine and/or iodide in the dimethylbenz[a]anthracene (DMBA) mammary cancer model in rats. The results show that 0.1% iodine or iodide increases the expression of peroxisome proliferator-activated receptor type γ (PPARγ), triggering caspase-mediated apoptosis pathways in damaged mammary tissue (DMBA-treated mammary gland) as well as in frank mammary tumors, but not in normal mammary gland. DMBA treatment induces the expression of lactoperoxidase, which participates in the antineoplastic effect of iodide and could be involved in the pro-neoplastic effect of estrogens, increasing the formation of DNA adducts. In conclusion, our results show that a supplement of 0.1% molecular iodine/potassium iodide (0.05/0.05%) exert antineoplastic effects, preventing estrogen-induced DNA adducts and inducing apoptosis through PPARγ/caspases in pre-cancer and cancerous cells. Since this iodine concentration does not modify the cytology (histology, apoptosis rate) or physiology (triiodothyronine and thyrotropin) of the thyroid gland, we propose that it be considered as an adjuvant treatment for premenopausal mammary cancer.

Inhibition of intrathyroidal dehalogenation by iodide.

Iodide is a trace element and a key component of thyroid hormones (TH). The availability of this halogen is the rate-limiting step for TH synthesis; therefore, thyroidal iodide uptake and recycling during TH synthesis are of major importance in maintaining an adequate supply. In the rat, the thyroid gland co-expresses a distinctive pair of intrathyroidal deiodinating enzymes: the thyroid iodotyrosine dehalogenase (tDh) and the iodothyronine deiodinase type 1 (ID1). In the present work, we studied the activity of these two dehalogenases in conditions of hypo- and hyperthyroidism as well as during acute and chronic iodide administration in both intact and hypophysectomized (HPX) rats. In order to confirm our observations, we also measured the mRNA levels for both dehalogenases and for the sodium/iodide symporter, the protein responsible for thyroidal iodide uptake. Our results show that triiodothyronine differentially regulates tDh and ID1 enzymatic activities, and that both acute and chronic iodide administration significantly decreases rat tDh and ID1 activities and mRNA levels. Conversely, both enzymatic activities increase when intrathyroidal iodide is pharmacologically depleted in TSH-replaced HPX rats. These results show a regulatory effect by iodide on the intrathyroidal dehalogenating enzymes and suggest that they contribute to the iodide-induced autoregulatory processes involved in the Wolff-Chaikoff effect.

Type 1 deiodinase activity and generation of triiodothyronine (T3) in prostate of sexually active rats.

BACKGROUND: Thyroxine (T(4)) and triiodothyronine (T(3)) are involved in the development and function of the male reproductive system. The type 1 deiodinase enzyme (D1) plays a major role in the intracellular conversion of T(4) to the active form, T(3). D1 is expressed in the prostate of pubescent rats, but it is unknown whether locally generated T(3) is involved in the development and function of this gland. METHODS: D1 activity was analyzed in prostates from neonatal to old rats. Local T3 generation (D1 and T3 levels) was evaluated in adult animals with 1-5 months of continuous sexual activity. D1 activity was measured by the radiolabeled-iodide-release method and T(3) concentration by radioimmunoassay. Secretory activity of the prostate was evaluated by a morphological analysis of epithelium (hematoxilin-eosin stain) and by measuring the activity of acid phosphatase as a marker enzyme for secretion. RESULTS: The highest prostate D1 activity was expressed around puberty, and it was almost undetectable during the neonatal period and with aging. Interestingly, 1 and 4 months of sexual activity avoided the decrease of D1 activity associated with aging. Sexual activity provoked a hypertrophy and functional hyperplasia in all lobes, but D1 and acid phosphatase activity increased only in the ventral lobe. D1 activity correlated with an increase in the prostatic T(3) concentration. CONCLUSIONS: The increased local generation of T(3) in prostate might be related to: (1) the differentiation/maturation that occurs at puberty and (2) the energy expenditure associated with maintaining the secretory activity of the glandular epithelium.

Antineoplastic effect of iodine in mammary cancer: participation of 6-iodolactone (6-IL) and peroxisome proliferator-activated receptors (PPAR).

INTRODUCTION: Studies in mammary cancer demonstrated that moderately high concentrations of molecular iodine (I2) have a antiproliferative and apoptotic effect either in vivo as in vitro, however the cellular intermediated involved in these effects has not been elucidated. METHODS: Virgin Sprague-Dawley rats were treated with methyl-nitrosourea (MNU: single dose ip, 50 mg/Kg bw) and the participation of arachidonic acid (AA) and PPAR receptors in the antineoplasic effect of I2 where analyzed. RESULTS: I2-treated rats for four weeks exhibited a significant reduction in the incidence (62.5 vs. 100%) and size (0.87 +/- 0.98 vs 1.96 +/- 1.5 cm3) of mammary tumors. HPLC analysis showed that tumoral but not normal mammary tissue contained an elevated basal concentration of AA and significantly more AA-iodinated called 6-iodolactone (6-IL) after chronic I2 treatment. Tumors from I2-treated rats showed fewer cells positive to proliferating cell nuclear antigen, lower blood vessel density, as well as decreases in vascular endothelial growth factor, urokinase-type plasminogen activator, and PPAR type alpha (PPARalpha). These same tumors showed increases in the cell death markers, TUNEL-positive cells (p < 0.05) and the enzyme caspase-3 (trend), as well as significant induction of PPAR type gamma (PPARgamma). CONCLUSION: Together, these data demonstrate that the antineoplasic effect of iodine involves 6-IL formation and PPARgamma induction.

Accidentes de trabajo atendidos en una Institución para población abierta, en México D. F. / Workers attended at public hospitals of occupational accidents, México D. F.

Objetivos principales y alcances: Esta investigación describe aspectos de frecuencia, consecuencias y problemas con el registro de accidentes laborales atendidos en hospitales de la Secretaría de Salud del Distrito Federal (SSDF). Método: Se revisaron 100 expedientes clínicos de los archivos de hospitales de la Secretaría de Salud del Distrito Federal, fueron determinadas las características de los casos de estudio en función de ocupación y otros aspectos laborales, identificamos factores que intervinieron en la frecuencia de accidentes en el trabajo, el tipo de daño y la gravedad; así como los días de hospitalización, tratamiento y secuelas. Realizamos análisis estadístico univariado y bivariado de las principales características estudiadas. Conformamos grupos de trascendencia de acuerdo al daño sufrido y analizamos la relación de éste con la edad, sexo, ocupación y formalidad del empleo. Resultados: La edad de los trabajadores osciló entre los 7 y los 72 años, con un promedio de 29. El 75% de la población estudiada fue menor de 40, 6% entre 40 y 72 y el 19% menor de edad. La población masculina fue predominante, ya que sólo siete de los cien casos fueron de mujeres. El 38% de los trabajadores pertenecían a la economía informal y el 62% restante a la formal, pero la mayoría de los contratados no contaban con seguridad social, ya que solamente siete trabajadores de los 100 lo indicaron. Los datos sobre las características de los accidentes muestran que la gravedad es alta, el daño en promedio excedió las consideraciones de severo y moderado, la media en días de hospitalización fue de 9.7 por trabajador, pero un 75% permaneció más de 4 días en el hospital.

Main objectives and achievements: This investigation describes frequency, consequences and problems about admission, related on workers that have suffered occupational accidents related at hospital wards in Health Secretary Hospitals of Distrito Federal. Method: We checked 100 files out from the records of Health Secretary Hospitals, the characteristics of the studied cases were determined because of activity and other occupational labors, we could identify the kind of risk that were involved into frequency of occupational accidents, the danger and seriousness, as well as the days workers stayed at hospital, treatment s and side effects. We performed univariated and bivariated statistical analyses from the main characteristics studied. Also we created important groups in danger order to analyze the relation between this characteristic and age, sex, occupational labor and informal or formal work. Results: The age of the workers varied between 7 and 72 years, with an average of 29 years. The 75% of the studied cases were younger than 40 years, 6% were between 40 and 72 and the 19% were underage. Also, the majority of population was men, because only 7 workers were women. The 38% workers belonged to informal work and the other 62% were in the formal one, but most of the people, regardless they were contracted, didn’t have social security because only 7 of them mentioned it. All those data points show us that the seriousness of occupational accidents is high, because the media was exceeded further more than light or sever wounded. The average of stayed days at hospital was 9.7 per worker so, but the other 75% stayed more than 4.

Epididymis expresses the highest 5'-deiodinase activity in the male reproductive system: kinetic characterization, distribution, and hormonal regulation.

We characterized the enzymes that catalyze the deiodination of T(4) to T(3) in the male reproductive tract. Testis, epididymis (EPI), seminal vesicles, prostate, bulbourethral glands, spermatozoa, and semen were taken from sexually mature rats (300 g). Iodothyronine 5'-deiodinase (5'-D) activity was quantified by the radiolabeled-iodide-release method. 5'-D activity was 10-fold higher in EPI and semen than in the rest of the tissues. In EPI, semen, and prostate, the enzymatic activity was completely inhibited by 1 mm 6-n-propyl-2-thiouracil, whereas in the other tissues the inhibition was partial (50%). The high susceptibility to 6-n-propyl-2-thiouracil inhibition, a ping-pong kinetic pattern, and low cofactor (Michaelis Menten constant for dithiothreitol=0.7 mm) and high substrate (Michaelis Menten constant for reverse T(3)=0.4 microm) requirements indicate that EPI 5'-D corresponds to type 1 deiodinase (D1). Real-time RT-PCR amplification of D1 mRNA in this tissue confirms this conclusion. The highest EPI D1 expression occurred at the onset of puberty and sexual maturity, and in the adult, this activity was more abundant in corpus and caput than in the caudal region. EPI D1 expression was elevated under conditions of hyperthyroidism and with addition of 17beta-estradiol. Our data also showed a direct association between D1 and a functional epididymis marker, the neutral alpha-glucosidase enzyme, suggesting that local generation of T(3) could be associated with the development and function of EPI and/or spermatozoa maturation. Further studies are necessary to analyze the possible physiological relevance of 5'-D in the male reproductive system.

Mortality by homicide in homosexuals: characterization of the cases registered in Mexico between 1995 and 2000.

This work shows a first approximation to the magnitude and characteristics of mortality by homicide in homosexuals in Mexico using the cases registered between the years 1995 and 2000. A statistical analysis was performed of the homicides against homosexuals that were registered through the review of newspaper articles published by the National Press. Sex, age of the victims, kind and number of weapons used, wounds endured, and the situation in which the corpses found were registered. The greater mortality by homicide due to homosexual orientation was recorded in men (95%); it was found that the cases accumulated in the cohort of the third and fourth decades of their age (43%). The homicides were characterized by extreme violence which included the use of various arm types (33%) and wounds (32%). The most frequent situations that occurred were finding the corpses naked and tied (13%). The features of the homicide against homosexuals are associated to the general attributes of the predominant masculinity model; therefore, at a macro social level, some reasons are found in the social construction of homophobia. The degree of violence in these crimes adduces the consideration that they are hate crimes.

Uptake and gene expression with antitumoral doses of iodine in thyroid and mammary gland: evidence that chronic administration has no harmful effects.

Several studies have demonstrated that moderately high concentrations of molecular iodine (I(2)) diminish the symptoms of mammary fibrosis in women, reduce the occurrence of mammary cancer induced chemically in rats (50-70%), and have a clear antiproliferative and apoptotic effect in the human tumoral mammary cell line MCF-7. Nevertheless, the importance of these effects has been underestimated, in part because of the notion that exposure to excess iodine represents a potential risk to thyroid physiology. In the present work we demonstrate that uptake and metabolism of iodine differ in an organ-specific manner and also depend on the chemical form of the iodine ingested (potassium iodide vs. I(2)). Further, we show that a moderately high I(2) supplement (0.05%) causes some of the characteristics of the "acute Wolff-Chaikoff effect"; namely, it lowers expression of the sodium/iodide symporter, pendrin, thyroperoxidase (TPO), and deiodinase type 1 in thyroid gland without diminishing circulating levels of thyroid hormone. Finally, we confirm that I(2) metabolism is independent of TPO, and we demonstrate that, at the doses used here, which are potentially useful to treat mammary tumors, chronic I(2) supplement is not accompanied by any harmful secondary effects on the thyroid or general physiology. Thus, we suggest that I(2) could be considered for use in clinical trials of breast cancer therapies.

Deiodinase type 1 activity is expressed in the prostate of pubescent rats and is modulated by thyroid hormones, prolactin and sex hormones.

The aim of this study was to characterize the type of 5'-deiodinase activity in the prostate of pubescent rats (7-8 weeks), to establish its distribution in the lobes (ventral, dorsolateral, and anterior), and to analyze its modulation by prolactin (PRL), testosterone, dihydrotestosterone (DHT), and 17beta-estradiol (E(2)). Our results showed that the enzymatic activity was highly susceptible to inhibition by 6-n-propyl-2-thiouracil and gold thioglucose, its preferential substrate was reverse tri-iodothyronine (rT(3)), it exhibited a low dithiothreitol requirement (5 mM), and the apparent K(m) and V(max) values for substrate (rT(3)) were approximately 0.25 microM and 9.0 pmol liberated/mg protein per hour, respectively. All these characteristics indicate the preferential expression of type 1 deiodinase (D1), which was corroborated by demonstrating the presence of D1 mRNA in prostate. D1 activity was detected in all lobes and was most abundant in the dorsolateral. Although we detected type 2 deiodinase (D2) mRNA expression, the D2 activity was almost undetectable. D1 activity was enhanced in animals with hyperthyroidism and hyperprolactinemia, in intact animals treated with finasteride (inhibitor of local DHT production), and in castrated animals with E(2) replacement. In contrast, activity diminished in castrated animals with testosterone replacement. Our results suggest that thyroid hormones, PRL, and E(2) exert a positive modulation on D1 activity, while testosterone and DHT exhibit an inhibitory effect. D1 activity may be associated with prostate maturation and/or function.

Is iodine a gatekeeper of the integrity of the mammary gland?

This paper reviews evidence showing iodine as an antioxidant and antiproliferative agent contributing to the integrity of normal mammary gland. Seaweed is an important dietary component in Asian communities and a rich source of iodine in several chemical forms. The high consumption of this element (25 times more than in Occident) has been associated with the low incidence of benign and cancer breast disease in Japanese women. In animal and human studies, molecular iodine (I(2)) supplementation exerts a suppressive effect on the development and size of both benign and cancer neoplasias. This effect is accompanied by a significant reduction in cellular lipoperoxidation. Iodine, in addition to its incorporation into thyroid hormones, is bound into antiproliferative iodolipids in the thyroid called iodolactones, which may also play a role in the proliferative control of mammary gland. We propose that an I(2) supplement should be considered as an adjuvant in breast cancer therapy.

Inhibition of N-methyl-N-nitrosourea-induced mammary carcinogenesis by molecular iodine (I2) but not by iodide (I-) treatment Evidence that I2 prevents cancer promotion.

We analyzed the effect of molecular iodine (I2), potassium iodide (KI) and a subclinical concentration of thyroxine (T4) on the induction and promotion of mammary cancer induced by N-methyl-N-nitrosourea. Virgin Sprague-Dawley rats received short or continuous treatment. Continuous I2 treated rats exhibited a strong and persistent reduction in mammary cancer incidence (30%) compared to controls (72.7%). Interruption of short or long term treatments resulted in a higher incidence in mammary cancer compared to the control groups. The protective effect of I2 was correlated with the highest expression of the I-/Cl- transporter pendrin and with the lowest levels of lipoperoxidation expression in mammary glands. Triiodothyronine serum levels and Na+/I- symporter, lactoperoxidase, or p53 expression did not show any changes. In conclusion continuous I2 treatment has a potent antineoplastic effect on the progression of mammary cancer and its effect may be related to a decrease in the oxidative cell environment.

[Sequential changes of extracellular matrix metalloproteins in pregnancy and labor in the rat chorio-allantois]. / Cambios secuenciales de metaloproteinasas de matriz extracelular durante la gestación y el trabajo de parto en el corioalantoides de la rata.

Participation of matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) in the rupture of fetal membranes (FM) during labor has been proposed. We describe and characterize sequentially the activity of the enzymes that degrade connective tissue in the FM of the rat during pregnancy and labor. Pregnant Wistar rats were sacrificed on different days of gestation and samples of amniotic fluid (AF) and MCA were collected to be analyzed for proteolytic activity, zymography, western blot and northern blot. Results showed that during labor, there is a significant increase in the proteolytic activity in the MCA and in the AF. MMP-2 was identified from day 15 of pregnancy and it increased near labor. MMP-9 was only identified two days before labor. MMP-2 and MMP-9 mRNA expression were coincident with enzymatic activity and western blot data. During labor, TIMP-1 decreased and TIMP-2 did not change. These results allow us to conclude that there exists a quantitative and qualitative differential expression of MMPs during gestation, especially during labor.