Immunofluorescence Analysis of Estrogen and Progesterone Receptors and Ki-67 Nuclear Protein in Canine Uteri Treated with Medroxyprogesterone Acetate During Anestrus / Análisis de Inmunofluorescencia de Receptores de Estrógeno y Progesterona y Proteína Nuclear Ki-67 en Úteros Caninos Tratados con Acetato de Medroxiprogesterona Durante el Anestr

SUMMARY: Estradiol and progesterone receptors play an essential role in the changes occurring in the uterus during the estrus cycle in dogs (Canis lupus familiaris). In order to investigate the potential effect of progestational agent medroxyprogesterone acetate (MPA) when is used during anestrus on the expression of estradiol receptors [ER], progesterone receptors [PR] and nuclear protein Ki67, we evaluated uterine tissue immunohistochemically. Uteri were grouped as nulliparous (control, n=11), multiparous (n=11) and treated with MPA (n=11; nulliparous with two treatments; 5mg/kg; i.m.). The amount and location of PR, ER and Ki67 were studied on the epithelial surface, apical and basal regions of the endometrium and myometrium using immunohistochemical techniques with a spectral confocal microscope and analyzed by ANOVA. Differences in ER were observed between the multiparous and MPA-treated groups in the apical region of the endometrium (p=0.0022). Differences in cell proliferation were detected between the nulliparous and multiparous groups (p=0.0037) and nulliparous and MPA-treated groups (p=0.0003) in the basal region of the endometrium. In conclusion, two doses of MPA (5mg/kg; i.m.) do not have a significant effect on the expression of ER and PR; however, they inhibit cell proliferation in the basal region of the endometrium, which includes the stroma, subepithelial cell layer, compact layer, and spongy layer. The clinical and long-term effect of this treatment should be evaluated in subsequent studies.

Los receptores de estradiol y progesterona juegan un rol fundamental en los cambios que se producen en el útero durante el ciclo estral de las perras (Canis lupus familiaris). El objetivo de este estudio fue evaluar las expresiones de ER-a y PR en el útero y la proliferación de células endometriales detectando la expresión nuclear de la proteína Ki67 en perras expuestas a la progestina sintética MPA y compararlas con perras nulíparas y multíparas expuestas a progesterona luteal. Úteros fueron agrupados como nulíparas (control, n=11), multíparas (n=11) y tratadas con MPA (n=11; nulíparas con dos tratamientos; 5 mg/kg; i.m.). La expresión de PR, ER-a y Ki67 fue evaluada en la regiones apicales y basales del endometrio y miometrio con un microscopio confocal espectral. Se observó diferencias en ER-a entre los grupos multíparas y tratados con MPA en la región apical del endometrio (p=0,0022). Se detectaron diferencias en la proliferación celular entre los grupos de nulíparas y multíparas (p=0,0037) y los grupos de nulíparas y tratados con MPA (p=0,0003) en la región basal del endometrio. En conclusión, dos dosis de MPA (5mg/kg; i.m.) no tienen un efecto significativo sobre la expresión de ER y PR; sin embargo, inhiben la proliferación celular en la región basal del endometrio, el cual incluye a estroma, capa de células subepiteliales, estratos compacto y esponjoso. El efecto clínico a largo plazo de este tratamiento debe ser evaluado en estudios posteriores.

Prostaglandin F receptor expression in intrauterine tissues of pregnant rats

In this investigation, we studied the expression and localization of rat prostaglandin F (FP) receptor in uterine tissues of rats on gestational Days 10, 15, 18, 20, 21, 21.5 and postpartal Days 1 and 3 using Western blotting analysis, real-time PCR, and immunohistochemistry. A high level of immunoreactivity was observed on gestational Days 20, 21, and 21.5 with the most significant signals found on Day 20. FP receptor protein was expressed starting on gestational Day 15, and a fluctuating unsteady increase was observed until delivery. Uterine FP receptor mRNA levels were low between Days 10 and 18 of gestation (p < 0.05). The transcript level increased significantly on Day 20 and peaked on Day 21.5 just before labor (p < 0.05). There was a positive correlation between FP receptor mRNA expression and serum estradiol levels (rs = 0.78; p < 0.01) along with serum estradiol/progesterone ratios (rs = 0.79; p < 0.01). In summary, we observed an increase FP receptor expression in rat uterus with advancing gestation, a marked elevation of expression at term, and a concominant decrease during the postpartum period. These findings indicate a role for uterine FP receptors in the mediation of uterine contractility at term.

Effect of Naja naja Laurenti shed skin extract on estrous cycle, hormone - cytokine profiles, histopathology of ovary and uterus of Swiss albino mice.

The snake shed skin though considered as biological waste products have been mentioned in folk and traditional medicine for treatment of ailments like skin disorders, parturition problems etc. Shedded skin extract (5 mg.kg-1, sc) did not produce any change in the estrous cycle of normal cycling female mice. However in 10 mg.kg-1, sc dose, the extract caused a temporary cessation of the estrous cycle at diestrous phase in normal cycling female mice for 10 days. SSAE (10 mg.kg-1, sc) caused a significant change in the level of LH, FSH, progesterone, estradiol, IL-1β, IL-6 and TNF-α. Histopathology of uterus and ovary showed structural disorientation in both. The results substantiate the influence of snake shed skin in mice reproductive cycle.

Alterações histopatológicas pancreáticas, placentárias e na matriz extracelular hipofisária durante a diabetes mellitus gestacional / Pancreatic histopathological changes, placental and the pituitary extracellular matrix during gestational diabetes mellitus

A Diabetes Mellitus Gestacional (DMG) pode ser definida como intolerância a carboidrato durante a gravidez e estima-se que pode afetar 10-22% de todas as pacientes grávidas. Durante a gravidez podem surgir diversas complicações para o feto como risco elevado de aborto espontâneo, anormalidades congênitas e morbidade e mortalidade neonatal. Entretanto, podem surgir também alterações morfofuncionais em diversos órgãos da mãe diabética, porém isso não é bem estabelecido. Investigar se haverá ou não alterações bioquímicas e histopatológicas em diversos órgãos, como hipófise, útero, placenta e pâncreas de ratas grávidas com diabetes mellitus durante e no final da gravidez e compará-las . Além disso, investigar se há alteração na matriz extracelular (MEC) da hipófise desses animais. No 5º dia de vida, ratas Wistar foram divididas em dois grupos: um tratado com estreptozotocina (Grupo Diabético / DIAB), na dose de 90 mg/kg, subcutâneo e outro grupo, que foi tratado com veículo (tampão citrato/CTR). Aos 90 dias de vidas, foram submetidas ao cruzamento. Após isso, foram sacrificadas no 11º e 21º dia de gravidez. Foram avaliados glicemia e bioquímica maternal e número de implantes .O pâncreas, útero, placenta e hipófises foram coradas com Hematoxilina e Eosina e somente as hipófises foram coradas com Massom e Picrosirius, para avaliação da MEC.Os animais diabéticos tanto do 11º quanto do 21º dia apresentaram uma redução no número de implantes, menor peso e maior glicemia e colesterol total, em relação aos animais controle independente do dia da gravidez. Não foi verificada diferença dos níveis de triglicerídeos entre os grupos não diabéticos e diabéticos, independente dos dias. Entretanto, os animais diabéticos que finalizaram o período de gestação apresentaram uma maior glicemia maternal em relação ao grupo diabético do 11º dia. Pâncreas de ratas diabéticas do 21º dia apresentaram vacuolização intracitoplasmática das ilhotas, insulite,migração de células ...

Gestational Diabetes Mellitus (GDM) can be defined as carbohidrat intolerance during pregnancy and it may affect 10-22% off all pregnant pacients. During pregnancy can surge lots of complications to the fetus such as high risk of spontaneous abortion, congenital abnormalities and neonatal morbity and mortality. However, it can also surge morphofunctional alterations in several organs of the diabetic mother, but it has not been well established .To investigate if there is going to be biochemical and histopathological alterations in several organs, such as pituitary, uterus, placenta and pancreas of pregnant diabetics rats during and in the end of pregnancy and compared them. Furthermore, to investigate if there is pituitary alteration of the extracellular matrix (ECM) in these animals. On the 5th day of life, Wistar rats were divided in two groups: one treated with streptozotocin (Diabetic Group/DIAB) , with the dose of 90 mg/kg, subcutaneous and another group , treated with vehicle (citrate buffer/CTR). At 90 days of life, they were mated . After, they were sacrified at 11o e 21o days of pregnancy. Were evaluated maternal glicemia and biochemistry and implant numbers. The pancreas, uterus,placenta e pituitary were stained with Hematoxilin and Eosin and only the pituitary were stained with Masson and Picrosirius, for ECM evaluation. Diabetic animals of 11o day as well as 21o days during pregnancy showed a reduced implant numbers, reduced weight and higher glicemia and total cholesterol , compared with control animals independent of pregnancy day. It was not verified difference in triglycerides levels between non diabetic and diabetic animals, independent of the day. However, diabetic animals that concluded the gestational period showed a higher maternal glicemia compared with 11o day diabetic group. Pancreas of 21o days diabetic animals showed islets intracitoplasmatic vacuolization, insulitis, inflammatory cell migration, thickness of wall vessel ...

The role of inflammation and matrix metalloproteinases in equine endometriosis

Equine endometriosis is a multifactorial disease considered to be a major cause of equine infertility. The purpose of this study was to evaluate the reliability of histomorphological grading for biopsy-like samples compared to entire uterine wall samples, to examine the association between the degree of endometriosis with animal age, and to investigate the role of inflammation in endometriosis and the expression of different matrix metalloproteinases in equine endometrium. Histomorphological lesions in 35 uterine samples were examined while comparing biopsy-like samples and entire-wall samples. Seventeen uterine samples were stained with antibodies against MMP-2, MMP-9, MMP-14, and TIMP-2. The morphologic evaluation results of the biopsy-like tissue and entire-wall samples were significantly correlated. Endometriosis in older mares (>12 years of age) was more severe than in young mares (2~4 years of age), confirming the positive correlation between animal age and disease severity, while inflammation was poorly related to the degree of endometriosis. MMP-2 and MMP-14 were detected in stromal cells, while MMP-9 and TIMP-2 were both found in stromal and glandular epithelial cells. There were no significant differences in MMPs expression between the two groups (young vs. old mares). Additional studies on the activity of MMPs could further define the role of these enzymes in equine endometriosis.

Porcine uterine and placental extracellular matrix molecules throughout pregnancy / Moléculas de la matríz extracelular placentaria y uterina durante la preñez porcina

The molecules that constitute the extracellular matrix are important in several functions related to tissue support and cell-cell, cell-extracellular matrix interaction. Among the macromolecules that constitute the mentioned matrix we find osteopontin, fibrinogen and collagen. The present study was undertaken to analyze the rol of osteopontin, fibrinogen and collagen in uterine-placental interface during normal porcine gestation. Uterine and placental tissues from crossbred gilts of 30 (n=5), 60 (n=5), 70 (n=5) and 114 (at term, n=5) days of gestation were used. Macroscopic analysis of the embryos/fetuses allowed us to determine their gestational age by means of the crown-rump lenght. Haematoxylin-Eosin and Masson's Trichrome dyes along with light microscopy were used to structure analysis of every selected period of gestation. A spacial and temporal study of osteopontin and fibrinogen was performed through immunohistochemical technique. Determination of collagen fibers was carried out through Picrosirius red technique and polarizing microscopy. Results were expressed as semi-quantitative. Higher expression of osteopontin was observed at early periods of gestation, mainly in uterine and placental villi, endometrial gland epithelium and histotroph. Fibrinogen expressed abundantly in fetal mesenchyme in every period analyzed and in fetal and maternal vessels at Day 70. Negative expression of collagen fibers was observed in villi, however increasing expression of thick fibers throughout pregnancy was detected in uterine stroma and myometrium. These results confirm the importance of osteopontin, fibrinogen and collagen in the support of uterine and placental structures and in the suitable maintenance of pregnancy.

Las moléculas que constituyen la matriz extracelular son importantes en varias funciones relacionadas con el soporte del tejido y la interacción célula-célula, célula-matriz extracelular. Entre las macromoléculas que constituyen la matriz mencionada se encuentra la osteopontina, el fibrinógeno y el colágeno. Este estudio se realizó para analizar el rol de la osteopontina, el fibrinógeno y el colágeno en la interface útero-placentaria durante la gestación porcina normal. Tejidos uterinos y la placentarios de hembras porcinas cruzadas de 30 (n=5), 60 (n=5), 70 (n=5) y 114 (a término, n=5) días de gestación fueron utilizados. El análisis macroscópico de los embriones/fetos nos permitió determinar la edad gestacional por medio de la longitud cráneo-rabadilla. Tinciones de Hematoxilina-Eosina y Tricrómico de Masson con microscopía de luz se utilizó para estructurar el análisis de cada periodo de tiempo seleccionado de la gestación. Un estudio espacial y temporal de la osteopontina y el fibrinógeno se realizó mediante técnicas de inmunohistoquímica. La determinación de fibras colágenas se llevó a cabo a través de la técnica Picrosirius rojo por microscopia de polarización. Los resultados se expresaron como semi-cuantitativos. La expresión de osteopontina se observó en los primeros períodos de gestación, principalmente en las vellosidades del útero y la placenta, epitelio de las glándulas endometriales e histotrofos. El fibrinógeno se expresa abundantemente en mesénquima fetal en todos los períodos analizados y en los vasos fetales y maternos el día 70. Una expresión negativa de fibras colágenas se observó en las vellosidades, sin embargo, un aumento de expresión de las fibras gruesas durante la gestación se detectó en el estroma uterino y el miometrio. Estos resultados confirman la importancia de la osteopontina, fibrinógeno y colágeno en el soporte de las estructuras del útero y placenta, así como el mantenimiento adecuado durante la gestación.

Expression and regulation of Enpp2 in rat uterus during the estrous cycle

Ectonucleotide pyrophosphatase/phosphodiestrase 2 (Enpp2) isolated from the supernatant of human melanoma cells is a lysophospholipase D that transforms lysophosphatidylcholine into lysophospatidic acid. Although multiple analyses have investigated the function of Enpp2 in the hypothalamus, its role in the uterus during the estrous cycle is not well understood. In the present study, rat uterine Enpp2 was analyzed by RT-PCR, Western blotting, and immunohistochemistry. Quantitative PCR analysis demonstrated that uterine Enpp2 mRNA was decreased during estrus compared to proestrus and diestrus. To determine whether uterine Enpp2 expression is affected by sex steroid hormones, immature rats were treated with 17beta-estradiol (E2), progesterone, or both on postnatal days 14 to 16. Interestingly, the expression of Enpp2 mRNA and protein were down-regulated by E2 in the uterus during estrus but not during proestrus or diestrus, suggesting that Enpp2 may play a role in uterine function during estrus. Enpp2 is primarily localized in the stromal cells of the endometrium during proestrus and estrus. During diestrus, Enpp2 was highly expressed in the epithelial cells of the endometrium. Taken together, these results suggest that uterine Enpp2 may be regulated by E2 and plays a role in reproductive functions during female rat development.

CD10 in diffuse uterine leiomyomatosis: a case report along with a few comments on histogenesis.

Diffuse uterine leiomyomatosis (DUL) is a rare entity with an unknown etiopathogenesis. A 24 years old female presented with abdominal discomfort and menorrhagia. Clinical and ultrasonographic examination revealed an enlarged uterus. The hysterectomy specimen showed a symmetrically enlarged uterus with a bosselated external surface. The cut surface showed multiple nodules of varying sizes diffusely involving the myometrium. Microscopically, the nodules were leiomyomas of varying degrees of cellularity. Some of the leiomyomas showed an increased vascularity either in the form of congeries of blood vessels with a lobular arrangement or occasionally as foci of 2-3 vessels. The vessels were surrounded by whorls of spindle cells. On immunohistochemistry the leiomyomas expressed vimentin, smooth muscle actin (SMA), desmin and CD10: the cells whorling around the blood vessels expressed vimentin, SMA and focally desmin and were negative for CD10 and HMB-45. The aim of this paper is to document that CD10 is expressed in diffuse uterine leiomyomatosis and discuss the histogenesis of DUL.

Implication of ADAM-8, -9, -10, -12, -15, -17, and ADAMTS-1 in Implantational Remodeling of a Mouse Uterus

In the present study, whether the ADAM-8, -9, -10, -12, -15, -17, and ADAMTS-1 proteins might play a role in mouse uterus during periimplantation period was investigated. Immunoblotting analyses demonstrated that all ADAM proteins consistently appeared throughout days 1 to 8 of pregnancy but with a variation depending on the species of ADAM gene, the progression of pregnancy, and the site of the uterus. Immunohistochemical analyses indicated that ADAM proteins were localized in the luminal or glandular epithelial layers with a varying intensity depending on the species of ADAM and the progression of pregnancy. Particularly ADAM-8, -12, and -15, were predominantly located in the implantation site of the uterine tissues, whereas little or no protein was localized in the interimplantation site. Based upon these observations, it is suggested that the ADAMs might play an important role in the remodeling of the mouse uterus during the periimplantation period.

RNA fingerprinting using RAP-PCR identifies an EBAF homologue mRNA differentially expressed in rat oviduct

As a step towards the identification of genes preferentially expressed in the oviduct during early rat embryo development, we isolated a cDNA fragment (Pr14) by using RNA arbitrarily primed PCR (RAP-PCR), being its expression restricted to oviduct and uterus; its mRNA is mainly expressed in oviduct during late luteal phase and early pregnancy. This fragment is 100 per cent identical to a rat DNA sequence (Accession No. NW_047400)downstream the terminal exon of a Ratturs norvegicus gene (Locus Link Accession No. LOC289316) similar to ebaf (endometrial bleeding-associated factor), a novel member of the Transforming Growth Factor superfamily. Northern analyses showed that this sequence hybridizes with 2.9 kb and 4.1 kb mRNAs in early pregnant rat oviducts. However, only the 4.1 kb mRNA was detected in the oviduct of non-pregnant rats, showing an increase from proestrus to diestrus. The expression of this oviduct-uterus specific mRNA suggests that the products of this gene may play a role in the oviductal reproductive process.

Influence of antiangiogenic fraction from Diogenes avarus (Heller) on fertility and implantation in mice.

The methanol extract isolated from hermit crab, D. avarus degenerated ovarion and uterine tissues in cyclic and pregnant mice, treated before and after the implantation. Immunohistochemical staining using CD31 and Factor VIII specific to endothelial cells showed reduction in microvessel density. The hormonal assay showed decrease in the progesterone secretion in all experimental mice.

Pharmacological studies on the venomous spotted butterfish (Scatophagus argus Linn) sting extract on experimental animals.

A sting of the fish S. argus, a venomous edible spotted butterfish, produces tremendous local pain, severe swelling, rise of body temperature, throbbing sensation etc. To establish the pharmacological activities of S. argus sting extract, the present investigation, was carried out on experimental animals. The LD50 of extract was found to be 9.3 mg/kg (iv) in male albino mice. The extract showed loss of sensation, urination and salivation in mice. It potentiated pentobarbitone induced sleeping time in male albino mice and produced hypothermia. Extract produced a fall of cat and guinea pig blood pressure, which was completely abolished by mepyramine. It produced a transient reduction of respiratory rate in rat, but decreased respiratory amplitude in cat, which was abolished after vagotomy. On isolated toad heart, the extract increased both the amplitude and rate of contraction. On isolated guinea pig heart, the sting extract decreased both the rate and amplitude of contraction leading to cardiac arrest, but it had no effect on isolated guinea pig auricle. The extract produced a reversible blockade of electrically induced twitch response of isolated chick biventer cervices preparation, but it had no effect on the isolated rat phrenic nerve diaphragm preparation. It produced a slow contractile response on isolated guinea pig ileum, rat uterus and rat fundal strip preparations but produced slow relaxation on isolated rat duodenum preparation. The contractile response on isolated guinea pig ileum and rat fundal strip was antagonised by SC19220. It did not produce any significant cutaneous haemorrhage in mice and did not produce any haemolysis on saline washed erythrocytes. The sting extract significantly increased capillary permeability of guinea pig dorsal flank and produced oedema in mice hind paw.

Uterine mast cells: a new hypothesis to understand how we are born

Birth is the result of complex, well-defined, and coordinated events, that are tightly regulated by endocrine, nervous, and immune responses, and take place primarily in the female reproductive tract. Various mechanisms and mediators involved in pregnancy, labor, and delivery, are highly conserved among different mammalian species and mast cells emerge as potential and crucial participants in these processes, as it is discussed in this review.

Nicotine induced alterations on reproductive organs of female rats under protein deficient condition.

Nicotine causes decrement in body weight, reduction in ovarian and uterine weight, irregularity in estrous cycle and histological damage in ovary and uterus in rats maintained on normal (18% casein) and protein restricted diet (5% casein). The degree of nicotine toxicity increases in protein inadequacy.

Expression of nuclear factor-kappaB in mouse uterus during peri-implantation / 华中科技大学学报（医学）（英德文版）

To investigate the expression of the subunit p65 of NF-kappaB and inhibitor kappa B alpha (IkappaBalpha) in mouse uterus during peri-implantation, thereby investigating whether transient activation of nuclear factor-kappaB (NF-kappaB) takes place during embryo implantation in mice. Immunohistochemical technique was used to examine the expression and localization of p65 in endometrium or deciduas, and Western blot analysis was employed to detect the levels of IkappaBalpha protein in mouse endometrium or deciduas. P65 protein was detected in stromal cells, epithelial cells of endometrium as well as in myometrium. Staining was predominately seen in the cytoplasm of the cells. Staining intensity for p65 was stronger in the epithelial compartment than the stromal compartment and myometrium. Staining intensity increased slightly during pregnancy, and it reached a high level on pregnancy day 5 and day 8. In contrast to p65, the level of IkappaBalpha protein was lowest on pregnancy day 5 in all groups. Our results suggested that NF-kappaB may regulate embryo implantation by its transient activation in mice.

Reacción acrosómica e hipercolesterolemia: análisis de un modelo experimental / Acrosome reaction and hipercholesterolaemia: analysis of an experimental model

Se estudiaron los niveles lipídicos y proteícos del fluido uterino y oviductal de conejas blancas de Nueva Zelandia NZW hipercolesterolémicas y su relación con la capacidad fecundante de espermatozoides homólogos. Hembras hipercolesterolémicas en estro presentaron nivele aumentados de colesterol tanto en fluido uterino como oviductal, mientras los niveles de fosfolípidos aumentaron solo en fluido uterino, en fluido oviductal hubo aumento en la relación colesterol: fosfolípidos. Las proteínas totales no mostraron variación a lo largo del ciclo y del tratamiento. La cinética de la reacción acrosómica de espermatozoides controles, en medio capacitante para conejos fue la misma que cuando se utilizó fluido uterino u oviductal de hembras controles o hipercolesterolémicas como medio capacitante in vitro. El aumento de colesterol observado en fluido uterino y oviductal de las hembras tratadas, aunque fue estadísticamente significativo, respecto a los controles, probablemente no es suficiente para modificar el flujo de colesterol desde los gametos al medio y modificar así la cinética de la reacción acrosómica

Copper levels & reactive oxygen species in uterine flushings in copper intrauterine contraceptive device users.

Copper levels were estimated in the uterine flushings in 15 copper 'T' 200 device acceptors. There was a statistically significant difference in the preinsertion and one week post insertion values (P < 0.001). This also corresponded to a high level of generation of reactive oxygen species. The levels of reactive oxygen species were similar to preinsertion values at 4 and 12 wk. The copper values declined over the 3 months but were still higher at 12 wk as compared to preinsertion levels and this difference was statistically significant. Hence addition of copper to the intrauterine device besides enhancing the contraceptive efficacy, perhaps also plays an important role in microbicidal activity and helps in overcoming the infection introduced at the time of insertion.

Effect of IUCD on human uterine fluid protein concentration throughout the menstrual cycle.

Uterine fluid of 96 Women implanted with IUCD was collected and processed for protein estimation. The results obtained in women having IUCD were compared with those of parous/normal women. The trend of fluctuation in protein concentration was the same in both parous and women with IUCD. But comparatively the protein concentration in it was so much higher in women having IUCD throughout the menstrual cycle. The increased concentration may be responsible for making the fluid environment unfavourable for blastocyst as well as sperm metabolism.

Effects of dimethoate on collagen metabolism in rats.

The effects of three different doses of dimethoate on the collagen metabolism in the tissues of female albino rats were studied by measuring the specific and total activities of 3H-hydroxyproline in the dermal, gingival and uteral collagen fractions and in the urine. Compared to controls, the total activity of 3H-hydroxyproline in the soluble collagen and in the urine at 12 h after the administration of 3H-proline was significantly lower by 44.45 and 58.12 per cent in the higher dose (2.25 mg/100 g body weight) of dimethoate treated groups respectively. The urinary excretion of hydroxyproline and the total activity of urinary 3H-hydroxyproline measured after 28 days of injection of labelled proline were decreased by 45.56 and 32.68 per cent in higher doses of dimethoate treated animals respectively but the excretions of urinary 3H-hydroxyproline were decreased by 6.36 and 2.88 per cent in lower doses of dimethoate (0.56 mg/100 g body weight) treated animals. The results of the present investigation clearly indicate that the synthesis of collagen is decreased in the higher doses of dimethoate treated animals compared to lower doses of dimethoate treated animals. In addition, the rates of catabolism of both soluble and insoluble collagens were decreased in higher doses of dimethoate treated rats. In concludes that the lower doses of dimethoate (0.56 mg) treated rats were less affected than the higher doses of dimethoate (2.25 mg) treated rats.