2,4-dichlorophenoxyacetic acid (2,4-D) exposure during postnatal development alters the effects of western diet on mouse prostate.

Western diet (WD), abundant in saturated fats and simple carbohydrates, has been associated with the development of prostate diseases. In addition, 2,4-dichlorophenoxyacetic acid (2,4-D), an herbicide used in agricultural and non-agricultural settings, may interfere with the endocrine system impacting reproductive health. The association of both factors is something common in everyday life, however, there are no relevant studies associating them as possible modulators of prostatic diseases. This study evaluated the action of the herbicide 2,4-D on the postnatal development of the prostate in mice fed with WD. Male C57Bl/6J mice received simultaneously a WD and 2,4-D at doses of 0.02, 2.0, or 20.0 mg/kg b.w./day for 6 months. The prolongated WD intake induced obesity and glucose intolerance, increasing body weight and fat. WD induced morphological changes and increased PCNA-positive epithelial cells in prostate. Additionally, the WD increased gene expression of AR, antioxidant targets, inflammation-related cytokines, cell repair and turnover, and targets related to methylation and miRNAs biosynthesis compared to the counterpart (basal diet). 2,4-D (0.02 and 2.0) changed prostate morphology and gene expression evoked by WD. In contrast, the WD group exposed to 20 mg/kg of 2,4-D reduced feed intake and body weight, and increased expression of androgen receptor and genes related to cell repair and DNA methylation compared to the negative control. Our results showed that 2,4-D was able to modulate the effects caused by WD, mainly at lower doses. However, further studies are needed to elucidate the mechanisms of 2,4-D on the obesogenic environment caused by the WD.

Nandrolone decanoate and resistance exercise affect prostate morphology and hormone receptor interface in adult rats with implications for the aging process.

BACKGROUND: Nandrolone decanoate (ND) is an anabolic-androgenic steroid, and its indiscriminate use leads to subclinical alterations in the hypothalamic-pituitary-gonadal axis and androgen-dependent organs. OBJECTIVES: To evaluate the effects of ND, either alone or in combination with resistance exercise (RE), on the levels of sex hormones, converting enzymes, and steroid receptors and the morphology of the ventral prostate (VP) in adult and aged rats. METHODS: Forty Sprague-Dawley adult and aged rats were divided into four groups each, sedentary and trained with and without ND. The groups received treatments over 8 weeks. Adult animals were sacrificed immediately following treatment completion, while the aged groups were left untreated until 300 days of age. RESULTS: Adult and aged animals showed reductions in testosterone levels following the different treatments, and 17ß-estradiol levels were decreased in the ND-treated groups. The level of 5α-reductase type 2 (5αR2) and aromatase was increased significantly in the prostates of adult animals that performed RE. However, aromatase levels were decreased in the prostates of aged animals that performed RE and were treated with ND, while 5αR2 levels were reduced in aged animals that performed RE without ND treatment. When sex receptors levels were examined, the aged and trained animals presented low androgen receptor (AR) levels. Estrogen receptors (ERs) levels were increased in the prostates of adult animals that received ND. ERß levels were reduced after treatments in aged animals. The heights of the prostatic epithelium were reduced in all adult treated animals, coinciding with increases in PCNA and PAR4 levels. DISCUSSION: ND and RE alter the levels of hormone, converting enzymes, and sex steroid receptors and the morphology of the VP. These effects were observed in both adult and aged rats. CONCLUSION: ND, either with or without RE, during post-puberty stage is able to interfere with the morphophysiology of the prostate.

Adjuvant-induced arthritis affects testes and ventral prostate of Wistar rats.

BACKGROUND: Rheumatoid arthritis (RA) may reduce the testosterone production, thereby leading to testicular dysfunction and subfertility. OBJECTIVES: This study aimed to evaluate whether adjuvant-induced arthritis (AIA) induces histopathological and morphometric-stereological alterations on testes with repercussions on the prostate, and alternatively, verifying AIA-induced direct effects on the prostate, regardless of the testicular involvement. MATERIAL AND METHODS: Adult male Wistar rats were sham-orchiectomized or orchiectomized. Twenty days after the surgery, these animals were injected with vehicle (SHAM and ORQ groups, respectively) or adjuvant (Mycobacterium tuberculosis) to induce arthritis (AIA and ORQ/AIA groups, respectively). Forty days later, testes and ventral prostate were processed for histopathological and morphometric-stereological analyses, as well as to PCNA immunohistochemistry. Collagen deposit was evaluated in prostate. Circulating testosterone levels were determined 15 days post-AIA induction in SHAM and AIA rats and 40th day in all groups. RESULTS: In the testes, AIA promoted histopathological changes characterized by an increase in the percentage of abnormal tubules and reduction in the height of the seminiferous epithelium, daily production of spermatozoa, and cellular proliferation. In the prostate, AIA decreased the luminal volume of the secretory ducts. In condition of androgenic deprivation due to the orchiectomy, AIA induced proliferation of the prostatic epithelium. DISCUSSION: The effects of arthritis on testes and prostate were observed 40 days post-AIA induction, possibly results of the hypoandrogenism were already established on 15th day post-induction, which is related to the decline of the steroidogenesis in the Leydig cells. On the other hand, the joint inflammatory process may also have direct repercussions upon the prostate, regardless of this hypoandrogenism. CONCLUSION: AIA effects on reproductive tissues may be related to both hypoandrogenism and other direct inflammatory mechanisms. Possibly, these AIA effects on the testes and prostate occur at a stage in which the inflammatory process is most active, about 15-20 days after induction, remaining evident until the 40th day.

Effect of low radiation dose on the expression and location of aquaporins in rat submandibular gland.

Head and neck cancers are common in several regions of the world and the treatment usually includes radiotherapy. This treatment can generate adverse effects to the salivary flow, with a relationship between the dose and the damage caused. Salivary gland cells are highly permeable to water and therefore, they express aquaporins (AQPs). This study analyzed changes in the expression and location of these proteins and identified morphological changes induced by low radiation in rat submandibular gland. Female rats were divided into control and irradiated groups. Immunohistochemistry analysis allowed confirming the presence of AQP1 in the blood vessel endothelium. Intense and steady labelling granules were also observed in the cytoplasm of submandibular gland ductal cells. In addition, there was AQP5 positive labelling in ductal cells delimiting the lumen of intercalated duct, in the cytoplasm and membrane of acinar cells. Finally, the decrease of AQP labelling in irradiated animal glands validated their radiosensitivity. Thus, the decrease in AQP1 protein levels in the endothelium and AQP5 in gland ductal cells of irradiated animals may have hindered the removal of water from the lumen of ductal cells, inducing a delay in water absorption and triggering a slight lumen increase.

Aquaporin 9 is expressed in the epididymis of immature and mature pigs.

Aquaporins (AQPs) are channel proteins that facilitate the transepithelial and bidirectional movement of water. AQP9 is an aquaporin that is expressed in the mammalian epididymis. This water transport contributes to epididymal sperm concentration. This study aimed to examine the morphology of epididymal epithelium in piglets and boars, as well as the expression and immunolocalization of AQP9. The piglets presented an epididymal epithelium in differentiation with principal, basal and apical cells. The cellular population of the epididymal epithelium in boars consisted of principal, basal, apical, clear and narrow cells. The migratory cells known as halo cells were observed in the epididymis of both piglets and boars. AQP9 expression presented differences between piglets and boars. Moderate intensity of AQP9 immunoreaction was observed in the apical border of the epididymal epithelium of the caput and cauda regions in the piglet epididymis. A moderate-to-intense reaction for AQP9 was observed in the nuclei of epithelial cells of the three epididymal regions in the boar epididymis. The region of the cauda epididymis showed reactivity for AQP9 also in the apical border of the epithelium. It is believed that the AQP9 is already functional in piglets at only 1 week of age and is more active, playing a pivotal role in the caput and cauda regions of the epididymis. Moreover, the intense AQP9 expression in the apical border of epithelial cells in the cauda region of the boar epididymis suggests a higher performance of AQP9 in this region, where sperm complete their maturation process, stored and concentrated.

Nandrolone decanoate and resistance exercise training favor the occurrence of lesions and activate the inflammatory response in the ventral prostate.

Age is a key factor in the development of prostatic lesions. An increase in reactive oxygen species levels occurs during aging. Furthermore, the indiscriminate use of anabolic androgenic steroids and physical exercise alter the availability of hormones and may promote the appearance of lesions. This study examined whether the use of nandrolone decanoate (ND), associated or not with resistance exercise training, affects the pathways related to the inflammatory response in the ventral prostate of adult and aged rats. Sprague-Dawley rats were distributed into eight experimental groups: sedentary with ND, sedentary without ND, exercise with ND, and exercise without ND. The animals performed resistance exercise training and received ND two times/week (5 mg/kg, i.m.) for 8 weeks. Adult rats were killed immediately following treatment completion, and aged rats remained untreated until reaching 300 days of age. The adult animals that received ND and performed resistance exercise training showed a higher occurrence of lesions with TLR4 activation. Marked IL-6 expression occurred in the group that performed resistance exercise training. The group exposed to ND showed overexpression of TLR2, TLR4, NOX1, Nrf2, TNF-α, and P38MAPK. The animals that received ND and performed training showed increase levels of NFκB, IRF3, IL-6, TNF-α, and NOX1. TLR2 and TLR4 showed no upregulation in the aged animals. The groups exercise + ND showed lesions in the adult stage and after aging, followed by molecular alterations. We concluded that nandrolone decanoate and resistance exercise training can promote the onset of prostatic tumors in the adult stage, and during aging, activating pathways involved in the inflammatory response.

Immunolocalization of Aquaporins 1 and 9 in the Ram Efferent Ducts and Epididymis.

Aquaporins (AQPs) are essential membrane protein channels for the transport of water across membranes. Fluid movement in the epididymis is important for modulation of the luminal environment, in which sperm mature and reside. This study was designed to understand the morphology and localization of AQPs in ram efferent ducts (ED) and epididymis. For this purpose, the epididymis of seven animals were removed for histologic and immunohistochemical analyses. AQP1 immunoreactivity was observed in the apex of the ED, and AQP9 was found adjacent to the nuclei of the epithelial cells of the ED. The epithelial lining of ram epididymis is pseudostratified columnar and presents principal, basal, apical and narrow cells. In the initial segment (IS), a moderate reaction for AQP1 was observed in the apical cytoplasm of epithelial cells. An intense reactivity for AQP1 was noted over the microvilli of principal cells and in spermatozoa in the caput. In the corpus and cauda, AQP1 was noted only over the endothelial cells of vascular channels located in intertubular spaces. A weak-to-moderate reaction for AQP9 was observed in the nuclei of epithelial cells in the IS, caput and corpus of the epididymis. In the cauda, an intense reaction to AQP9 was observed in the epithelial border. In the IS, caput and corpus, the reactivity for AQP9 differed from those observed in domestic animals. The cauda showed a pattern similar to that previously described. These results indicate that AQPs 1 and 9 have reversed locations and roles in rams, suggesting activity variations related with fluid and solute absorption throughout the epididymis.

Structure of the lining epithelium of the cauda epididymis of the golden hamster.

The ductus epididymis has roles in the maturation and storage of spermatozoa. The main function of the cauda epididymis is the storage of spermatozoa; however, this region exerts other morphophysiological roles. So, this study was aimed at investigating structural features of the cauda epididymis epithelium, which could indicate roles other than the storage. The relative percentages of the cell types in the epithelium were 74.9, 6.9, 12.5 and 5.6% of principal, clear, basal and halo cells respectively. Large intercellular spaces were seen among the lateral plasmatic membranes of adjacent principal cells or among these cells and others cell types. These spaces were found to be filled with multivesicular bodies, myelin figures, scrolls and debris of membranes or flocculent dense material. Clear cells had the cytoplasms filled with lysosomes ((3/4) of basal cytoplasm), and vacuoles and vesicles ((1/4) of apical cytoplasm). The observations allowed us to infer that clear cells could act in the process of endocytosis and also in water transfer from the lumen to the interstitium through the epithelium compartment. Moreover, transcytosis may occur at the cauda epididymis of Golden hamster.