Sncg, Mybpc1, and Parm1 Classify subpopulations of VIP-expressing interneurons in layers 2/3 of the somatosensory cortex.

Neocortical vasoactive intestinal polypeptide-expressing (VIP+) interneurons display highly diverse morpho-electrophysiological and molecular properties. To begin to understand the function of VIP+ interneurons in cortical circuits, they must be clearly and comprehensively classified into distinct subpopulations based on specific molecular markers. Here, we utilized patch-clamp RT-PCR (Patch-PCR) to simultaneously obtain the morpho-electric properties and mRNA profiles of 155 VIP+ interneurons in layers 2 and 3 (L2/3) of the mouse somatosensory cortex. Using an unsupervised clustering method, we identified 3 electrophysiological types (E-types) and 2 morphological types (M-types) of VIP+ interneurons. Joint clustering based on the combined electrophysiological and morphological features resulted in 3 morpho-electric types (ME-types). More importantly, we found these 3 ME-types expressed distinct marker genes: ~94% of Sncg+ cells were ME-type 1, 100% of Mybpc1+ cells were ME-type 2, and ~78% of Parm1+ were ME-type 3. By clarifying the properties of subpopulations of cortical L2/3 VIP+ interneurons, this study establishes a basis for future investigations aiming to elucidate their physiological roles.

Genetic Identification of Two Novel Loci Associated with Steroid-Sensitive Nephrotic Syndrome.

BACKGROUND: Steroid-sensitive nephrotic syndrome (SSNS), the most common form of nephrotic syndrome in childhood, is considered an autoimmune disease with an established classic HLA association. However, the precise etiology of the disease is unclear. In other autoimmune diseases, the identification of loci outside the classic HLA region by genome-wide association studies (GWAS) has provided critical insights into disease pathogenesis. Previously conducted GWAS of SSNS have not identified non-HLA loci achieving genome-wide significance. METHODS: In an attempt to identify additional loci associated with SSNS, we conducted a GWAS of a large cohort of European ancestry comprising 422 ethnically homogeneous pediatric patients and 5642 ethnically matched controls. RESULTS: The GWAS found three loci that achieved genome-wide significance, which explain approximately 14% of the genetic risk for SSNS. It confirmed the previously reported association with the HLA-DR/DQ region (lead single-nucleotide polymorphism [SNP] rs9273542, P=1.59×10-43; odds ratio [OR], 3.39; 95% confidence interval [95% CI], 2.86 to 4.03) and identified two additional loci outside the HLA region on chromosomes 4q13.3 and 6q22.1. The latter contains the calcium homeostasis modulator family member 6 gene CALHM6 (previously called FAM26F). CALHM6 is implicated in immune response modulation; the lead SNP (rs2637678, P=1.27×10-17; OR, 0.51; 95% CI, 0.44 to 0.60) exhibits strong expression quantitative trait loci effects, the risk allele being associated with lower lymphocytic expression of CALHM6. CONCLUSIONS: Because CALHM6 is implicated in regulating the immune response to infection, this may provide an explanation for the typical triggering of SSNS onset by infections. Our results suggest that a genetically conferred risk of immune dysregulation may be a key component in the pathogenesis of SSNS.

Importance of prostate androgen-regulated mucin-like protein 1 in development of the bovine blastocyst.

BACKGROUND: Prostate androgen-regulated mucin-like protein 1 (PARM1) is a pro-proliferative and anti-apoptotic glycoprotein involved in the endoplasmic reticulum (ER) stress response. A single nucleotide polymorphism in the coding region of PARM1 has been associated with competence of bovine embryos to develop to the blastocyst stage. Here we tested the importance of PARM1 for development by evaluating consequences of reducing PARM1 mRNA abundance on embryonic development and differentiation, gene expression and resistance to ER stress. RESULTS: Knockdown of PARM1 using an anti-PARM1 GapmeR did not affect competence of embryos to develop into blastocysts but decreased the number of trophectoderm (TE) cells in the blastocyst and tended to increase the number of cells in the blastocyst inner cell mass (ICM). Treatment of embryos with anti-PARM1 GapmeR affected expression of 4 and 3 of 90 genes evaluated at the compact-morula and blastocyst stage of development at days 5.5 and 7.5 after fertilization, respectively. In morulae, treatment increased expression of DAB2, INADL, and STAT3 and decreased expression of CCR2. At the blastocyst stage, knockdown of PARM1 increased expression of PECAM and TEAD4 and decreased expression of CCR7. The potential role of PARM1 in ER stress response was determined by evaluating effects of knockdown of PARM1 on development of embryos after exposure to heat shock or tunicamycin and on expression of ATF6, DDIT3 and EIF2AK3 at the compact morula and blastocyst stages. Both heat shock and tunicamycin reduced the percent of embryos becoming a blastocyst but response was unaffected by PARM1 knockdown. Similarly, there was no effect of knockdown on steady-state amounts of ATF6, DDIT3 or EIF2AK3. CONCLUSION: PARM1 participates in formation of TE and ICM cells in early embryonic development but there is no evidence for the role of PARM1 in the ER stress response.

Neurexophilin and PC-esterase domain family member 4 (NXPE4) and prostate androgen-regulated mucin-like protein 1 (PARM1) as prognostic biomarkers for colorectal cancer.

Owing to the high morbidity and mortality, novel biomarkers in the occurrence and development of colorectal cancer (CRC) are needed nowadays. In this study, the CRC-related datasets were downloaded from the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database. After screening the differentially expressed genes (DEGs) in R software, a total of 238 upregulated and 199 downregulated DEGs were revealed simultaneously. Then the Kaplan-Meier survival analysis and Cox regression analysis were used to reveal the prognostic function of these DEGs. Neurexophilin and PC-esterase domain family member 4 (NXPE4) and prostate androgen-regulated mucin-like protein 1 (PARM1) were two outstanding independent overall survival (OS) and relapse-free survival (RFS) prognostic genes of CRC in TCGA database. We next verified the expression of NXPE4 and PARM1 messenger RNA (mRNA) levels were significantly lower in CRC tumor tissue than in the adjacent noncancerous tissue in our clinical samples, and NXPE4 mRNA expression level was related to the tumor location and tumor size, while PARM1 was related to tumor location, lymph nodes metastasis, and tumor size. This study demonstrated that NXPE4 and PARM1 might be two potential novel prognostic biomarkers for CRC.

Trends of SHBG and ABP levels in male farmers: Influences of environmental fluoride exposure and ESR alpha gene polymorphisms.

A number of epidemiological studies have reported that chronic exposure to high concentrations of fluoride not only causes dental and skeletal fluorosis but additionally affects serum levels of reproductive hormones. However, possible interaction between fluoride exposure and estrogen receptor alpha (ESRα) gene polymorphisms on sex hormone-binding globulin (SHBG) and androgen binding protein (ABP) of male farmers has not been detailed. Here, we conducted a cross-sectional study including 348 male farmers with different fluoride exposure levels from drinking water in Henan province of China to explore effects of fluoride exposure and ESRα genetic variation on serum SHBG and ABP levels. We found serum SHBG levels in male farmers from the high exposure group to be lower than those of the low exposure group. We also found that concentrations of SHBG affected ABP levels. Furthermore, fluoride exposure and single nucleotide polymorphisms at the XbaI and rs3798577 loci of the ESRα gene affected serum ABP levels. Our findings suggest that chronic fluoride exposure from drinking water is associated with alterations of serum SHBG and ABP concentrations in local male farmers and that the effect of fluoride exposure on ABP levels vary depending on ESRα gene polymorphisms.

Sulphur dioxide and arsenic affect male reproduction via interfering with spermatogenesis in mice.

As two potential environmental hazards, sulphur dioxide (SO2) and arsenic have adverse effects on male reproduction, but the mechanism of which and their combined toxicity are not clear. In this study, we investigate male reproductive toxicity with a focus on spermatogenesis by treating mice with 5 mg/m3 SO2 and/or 5 mg/L arsenic. Our results showed that arsenic exposure caused significant decreases in water and food consumption and body weight in mice, whereas these changes were not observed in the SO2-only group. Both SO2 and arsenic reduced sperm counts, increased the percentage of sperm malformation, and induced abnormal testicular pathological changes. Elevated H2O2 and MDA contents, declined T-SOD activity, decreased spermatogenic cell counts, enhanced caspase-3 activity, and increased TUNEL-positive cells were also observed in mice exposed to SO2 and/or arsenic. Moreover, SO2 and arsenic co-exposure changed the mRNA levels of Bax and Bcl-2, decreased serum testosterone levels, and downregulated the expression of steroidogenic-related genes (LHR, StAR, and ABP) in mice. These findings provide a new theoretical basis for understanding how SO2 and arsenic interfere with spermatogenesis leading to infertility. These results also suggest that SO2 and arsenic co-exposure likely result in an additive effect on male reproductive toxicity in mice.

A differential cytokine expression profile before and after rFSH treatment in Sertoli cell cultures of men with nonobstructive azoospermia.

To evaluate the effects of follicle-stimulating hormone (FSH) treatment on cytokine gene expression in cultured Sertoli cells from men with nonobstructive azoospermia, a total of 15 azoospermic men diagnosed as obstructive azoospermia (OA) (n = 5) and nonobstructive azoospermia (NOA) (n = 10) were included in the study. NOA patients were split into two further subgroups: nFSH and hFSH serum FSH levels. Expression of cytokine gene panel (88 genes), FSHR and ABP was evaluated by real-time PCR array analysis. FSHR protein level was measured by the Western blot. In primary cultures of Sertoli cells, seven genes were found to be increased and 13 were decreased in NOA group, when compared to OA (p < .05). When rFSH was introduced into the culture media, expression of 12 genes in the NOA group restored a comparable level to those of the control OA group. Sertoli cells in all groups responded rFSH administration with increased expression of ABP. Our results suggest that FSH treatment may have positive effects on Sertoli cells of nonobstructive azoospermic patients via changing the expression levels of certain genes and restoring their levels in normal Sertoli cell population. Some cytokine levels can be considered as a potential candidate for detecting NOA patients. ABP is a good marker for cell viability and functionality in primary Sertoli cell culture.

Effects of long-term heat stress and dietary restriction on the expression of genes of steroidogenic pathway and small heat-shock proteins in rat testicular tissue.

The aim was to investigate the effects of long-term heat stress and dietary restriction on the expression of certain genes involving in steroidogenic pathway and small heat-shock proteins (sHSPs) in rat testis. Sprague Dawley rats (n = 24) were equally divided into four groups. Group I and II were kept at an ambient temperature of 22°C, while Groups III and IV were reared at 38°C for 9 weeks. Feed was freely available for Group I and Group III, while Group II and Group IV were fed 60% of the diet consumed by their ad libitum counterparts. At the end of 9 weeks, testicles were collected under euthanasia. Total RNA was isolated from testis tissue samples. Expression profiles of the genes encoding androgen-binding protein, follicle-stimulating hormone receptor, androgen receptor, luteinising hormone receptor, steroidogenic acute regulatory protein (StAR), cyclooxygenase-2 and sHSP genes were assessed at mRNA levels using qPCR. Long-term heat stress decreased the expression of StAR and HspB10 genes while dietary restriction upregulated StAR gene expression. The results suggested that long-term heat stress negatively affected the expression of StAR and HspB10 genes and the dietary restriction was able to reverse negative effect of heat stress on the expression of StAR gene in rat testis.

In Silico and In Vitro Investigation of the Piperine's Male Contraceptive Effect: Docking and Molecular Dynamics Simulation Studies in Androgen-Binding Protein and Androgen Receptor.

Understanding the molecular mechanism of action of traditional medicines is an important step towards developing marketable drugs from them. Piperine, an active constituent present in the Piper species, is used extensively in Ayurvedic medicines (practiced on the Indian subcontinent). Among others, piperine is known to possess a male contraceptive effect; however, the molecular mechanism of action for this effect is not very clear. In this regard, detailed docking and molecular dynamics simulation studies of piperine with the androgen-binding protein and androgen receptors were carried out. Androgen receptors control male sexual behavior and fertility, while the androgen-binding protein binds testosterone and maintains its concentration at optimal levels to stimulate spermatogenesis in the testis. It was found that piperine docks to the androgen-binding protein, similar to dihydrotestosterone, and to androgen receptors, similar to cyproterone acetate (antagonist). Also, the piperine-androgen-binding protein and piperine-androgen receptors interactions were found to be stable throughout 30 ns of molecular dynamics simulation. Further, two independent simulations for 10 ns each also confirmed the stability of these interactions. Detailed analysis of the piperine-androgen-binding protein interactions shows that piperine interacts with Ser42 of the androgen-binding protein and could block the binding with its natural ligands dihydrotestosterone/testosterone. Moreover, piperine interacts with Thr577 of the androgen receptors in a manner similar to the antagonist cyproterone acetate. Based on the in silico results, piperine was tested in the MDA-kb2 cell line using the luciferase reporter gene assay and was found to antagonize the effect of dihydrotestosterone at nanomolar concentrations. Further detailed biochemical experiments could help to develop piperine as an effective male contraceptive agent in the future.

Selection shaped the evolution of mouse androgen-binding protein (ABP) function and promoted the duplication of Abp genes.

In the present article, we summarize two aspects of our work on mouse ABP (androgen-binding protein): (i) the sexual selection function producing incipient reinforcement on the European house mouse hybrid zone, and (ii) the mechanism behind the dramatic expansion of the Abp gene region in the mouse genome. Selection unifies these two components, although the ways in which selection has acted differ. At the functional level, strong positive selection has acted on key sites on the surface of one face of the ABP dimer, possibly to influence binding to a receptor. A different kind of selection has apparently driven the recent and rapid expansion of the gene region, probably by increasing the amount of Abp transcript, in one or both of two ways. We have shown previously that groups of Abp genes behave as LCRs (low-copy repeats), duplicating as relatively large blocks of genes by NAHR (non-allelic homologous recombination). The second type of selection involves the close link between the accumulation of L1 elements and the expansion of the Abp gene family by NAHR. It is probably predicated on an initial selection for increased transcription of existing Abp genes and/or an increase in Abp gene number providing more transcriptional sites. Either or both could increase initial transcript production, a quantitative change similar to increasing the volume of a radio transmission. In closing, we also provide a note on Abp gene nomenclature.

Gibberellic acid acts as an agonist of steroidogenesis in male rats.

Testicular steroidogenesis has significant implication in male reproductive function. Although the effects of various signalling molecules on testicular functions have been studied earlier, the influence of the plant hormone gibberellic acid (GA3 ) on steroidogenesis has not been investigated. Acute (4 h) and subacute (15 days) studies using this compound through oral administration (150 µg day(-1) ) to groups of normal and diabetic Wistar male rats were therefore carried out. Results indicate that (i) enhanced activity of steroidogenic markers 3ß-hydroxysteroid dehydrogenase (3ß-HSD), 17ß-hydroxysteroid dehydrogenase (17ß-HSD), elevated tissue testosterone (T) content, increased steroidogenic acute regulatory protein (StAR) and androgen binding protein (ABP) levels with reduced lipid peroxidation and improved antioxidant defence in this treatment group of normal and diabetic rat testis, and (ii) elevated lipid peroxidation and diminished antioxidant defence, with insignificant change in 3ß-HSD and 17ß-HSD activity and testosterone level in acute treatment group of normal and diabetic rats testis, were noted. The observed increase in the activity of testicular 3ß-HSD and 17ß-HSD along with elevated testosterone content established GA3 as an inducer of steroidogenesis in rat.

[Potential detrimental effect of soy isoflavones on testis sertoli cells].

OBJECTIVE: To determine the effect of soy isoflavones on cell proliferation and the transcription levels of follicle-stimulating hormone receptor (FSHR), inhibin α (INHα), INHßB, androgen binding protein (ABP), transferrin (Tf) and vimentin in testis sertoli cells in SD rats. METHODS: Sertoli cells were cultured in vitro, exposed to daidzein at 0.03, 0.3, 3, and 30 µmol/L and genistein at 0.05, 0.5, 5 and 50 µmol/L, respectively. MTT was used to detect the proliferation of sertoli cells. Real-time PCR was used to detect the relative mRNA expressions of FSHR, INHα, INHßB, ABP, Tf and vimentin. RESULTS: Compared with control groups, cell proliferation and the relative mRNA expression levels of INHßB and ABP in the treated cells showed no significant alternation. The INHα mRNA expression levels were increased in 0.3 and 3 µmol/L Dai and 0.05 µmol/L Gen, while the mRNA expression levels of FSHR were downregulated in 30 µmol/L Dai and Gen at all concentrations. Tf mRNA expression levels were downregulated in 30 µmol/L Dai and 5 µmol/L and 50 µmol/L Gen, and the mRNA expression levels of vimentin were downregulated in 3 and 30 µmol/L Dai and 50 µmol/L Gen. CONCLUSION: Soy Isoflavones may have potential detrimental effect on the male reproductive system, as they may impact the function of sertoli cells by downregulating the transcription levels of some important proteins.

The role of retrotransposons in gene family expansions: insights from the mouse Abp gene family.

BACKGROUND: Retrotransposons have been suggested to provide a substrate for non-allelic homologous recombination (NAHR) and thereby promote gene family expansion. Their precise role, however, is controversial. Here we ask whether retrotransposons contributed to the recent expansions of the Androgen-binding protein (Abp) gene families that occurred independently in the mouse and rat genomes. RESULTS: Using dot plot analysis, we found that the most recent duplication in the Abp region of the mouse genome is flanked by L1Md_T elements. Analysis of the sequence of these elements revealed breakpoints that are the relicts of the recombination that caused the duplication, confirming that the duplication arose as a result of NAHR using L1 elements as substrates. L1 and ERVII retrotransposons are considerably denser in the Abp regions than in one Mb flanking regions, while other repeat types are depleted in the Abp regions compared to flanking regions. L1 retrotransposons preferentially accumulated in the Abp gene regions after lineage separation and roughly followed the pattern of Abp gene expansion. By contrast, the proportion of shared vs. lineage-specific ERVII repeats in the Abp region resembles the rest of the genome. CONCLUSIONS: We confirmed the role of L1 repeats in Abp gene duplication with the identification of recombinant L1Md_T elements at the edges of the most recent mouse Abp gene duplication. High densities of L1 and ERVII repeats were found in the Abp gene region with abrupt transitions at the region boundaries, suggesting that their higher densities are tightly associated with Abp gene duplication. We observed that the major accumulation of L1 elements occurred after the split of the mouse and rat lineages and that there is a striking overlap between the timing of L1 accumulation and expansion of the Abp gene family in the mouse genome. Establishing a link between the accumulation of L1 elements and the expansion of the Abp gene family and identification of an NAHR-related breakpoint in the most recent duplication are the main contributions of our study.

Viral dose, radioiodide uptake, and delayed efflux in adenovirus-mediated NIS radiovirotherapy correlates with treatment efficacy.

We have constructed a prostate tumor-specific conditionally replicating adenovirus (CRAd), named Ad5PB_RSV-NIS, which expresses the human sodium iodine symporter (NIS) gene. LNCaP tumors were established in nude mice and infected with this CRAd to study tumor viral spread, NIS expression, and efficacy. Using quantitative PCR, we found a linear correlation between the viral dose and viral genome copy numbers recovered after tumor infection. Confocal microscopy showed a linear correlation between adenovirus density and NIS expression. Radioiodide uptake vs virus dose-response curves revealed that the dose response curve was not linear and displayed a lower threshold of detection at 10(7) vp (virus particles) and an upper plateau of uptake at 10(11) vp. The outcome of radiovirotherapy was highly dependent upon viral dose. At 10(10) vp, no significant differences were observed between virotherapy alone or radiovirotherapy. However, when radioiodide therapy was combined with virotherapy at a dose of 10(11) vp, significant improvement in survival was observed, indicating a relationship between viral dose-response uptake and the efficacy of radiovirotherapy. The reasons behind the differences in radioiodide therapy efficacy can be ascribed to more efficient viral tumor spread and a decrease in the rate of radioisotope efflux. Our results have important implications regarding the desirable and undesirable characteristics of vectors for clinical translation of virus-mediated NIS transfer therapy.

Characterization and identification of PARM-1 as a new potential oncogene.

BACKGROUND: The Graffi murine retrovirus is a powerful tool to find leukemia associated oncogenes. Using DNA microarrays, we recently identified several genes specifically deregulated in T- and B-leukemias induced by this virus. RESULTS: In the present study, probsets associated with T-CD8+ leukemias were analyzed and we validated the expression profile of the Parm-1 gene. PARM-1 is a member of the mucin family. We showed that human PARM-1 is an intact secreted protein accumulating predominantly, such as murine PARM-1, at the Golgi and in the early and late endosomes. PARM-1 colocalization with α-tubulin suggests that its trafficking within the cell involves the microtubule cytoskeleton. Also, the protein co-localizes with caveolin-1 which probably mediates its internalization. Transient transfection of both mouse and human Parm-1 cDNAs conferred anchorage- and serum-independent growth and enhanced cell proliferation. Moreover, deletion mutants of human PARM-1 without either extracellular or cytoplasmic portions seem to retain the ability to induce anchorage-independent growth of NIH/3T3 cells. In addition, PARM-1 increases ERK1/2, but more importantly AKT and STAT3 phosphorylation. CONCLUSIONS: Our results strongly suggest the oncogenic potential of PARM-1.

Evolution of the ABPA subunit of androgen-binding protein expressed in the submaxillary glands in New and Old World rodent taxa.

The salivary androgen-binding proteins (ABPs) are members of the secretoglobin gene family present in mammals. Each ABP is a heterodimer assembled as an ABPA subunit encoded by an Abpa gene and linked by disulfide bridges to an ABPBG subunit encoded by an Abpbg gene. The ABP dimers are secreted into the saliva of mice and then transferred to the pelage after grooming and subsequently to the environment allowing an animal to mark territory with a biochemical signal. The putative role of the mouse salivary ABPs is that of pheromones mediating mate selection resulting in assortative mating in the Mus musculus species complex. We focused on comparing patterns of molecular evolution between the Abpa genes expressed in the submaxillary glands of species of New World and Old World muroids. We found that in both sets of rodents the Abpa genes expressed in the submaxillary glands appear to be evolving under a similar evolutionary regime, with relatively high nonsynonymous substitution rates, suggesting that ABP might play a similar biological role in both systems. Thus, ABP could be involved with mate recognition and species isolation in New World as well as Old World muroids.

False-positive TUNEL staining observed in SV40 based transgenic murine prostate cancer models.

The TRAMP (Transgenic Adenocarcinoma of the Mouse Prostate) and LADY (Probasin-large T antigen transgenic mouse) mice are widely used autochthonous models of prostate cancer. Both models utilise probasin promoters to direct androgen-regulated expression of oncogenic SV40 specifically to epithelial cells of the mouse prostate. The oncogenic processes and phenotypes which result mimic many features of human prostate cancer, making these transgenic mouse models useful experimental systems. The terminal deoxynucleotidyl transferase (Tdt)-mediated dUTP in situ nick end labelling (TUNEL) assay is a commonly used method for the detection of cells undergoing apoptosis. In this study, we demonstrate false-positive TUNEL staining in frozen prostate tissue from TRAMP and LADY mice, which was not observed in non-transgenic control animals and is not due to non-specific binding of labelled-dUTP substrate. The false-positive signal co-localised with large SV40 T-antigen expression. False-positive signal was apparent using multiple commercial TUNEL kits with different detection systems. These results caution against the use of the TUNEL assay for detection of apoptosis in frozen prostate tissue of large T-antigen based autochthonous transgenic models of prostate cancer.

Chemoprotective effects of kolaviron on ethylene glycol monoethyl ether-induced pituitary-thyroid axis toxicity in male rats.

Endocrine disrupting chemicals cause reproductive dysfunction by interacting with intricate regulation and cellular processes involve in spermatogenesis. This study investigated the probable mechanism of action of ethylene glycol monoethyl ether (EGEE) as an antiandrogenic compound as well as the effects of kolaviron upon co-administration with EGEE in rats. Adult male rats were exposed to EGEE (200 mg kg(-1) bw) separately or in combination with either kolaviron [100 (KV1) and 200 (KV2) mg kg(-1) bw] or vitamin E (50 mg kg(-1) bw) for 14 days. Western blot analysis revealed that the administration of EGEE adversely affected steroidogenesis in experimental rats by decreasing the expression of steroid acute regulatory (StAR) protein and androgen-binding protein (ABP). EGEE significantly decreased the activities of 3ß-hydroxysteroid dehydrogenase (3ß-HSD) and 17ß-hydroxysteroid dehydrogenase (17ß-HSD) but markedly increased sialic acid concentration in rat testes. EGEE-treated rats showed significant decreases in plasma levels of luteinising hormone (31%), testosterone (57.1%), prolactin (80.9%), triiodothyronine (65.3%) and thyroxine (41.4%), whereas follicle-stimulating hormone was significantly elevated by 76.9% compared to the control. However, co-administration of kolaviron or vitamin E significantly reversed the EGEE-induced steroidogenic dysfunction in rats. This study suggests that kolaviron may prove promising as a chemoprotective agent against endocrine pathology resulting from EGEE exposure.

[Influence of water fluoride exposure on sex hormone binding globulin and testosterone in adult male].

OBJECTIVE: To explore the influence of water fluoride exposure on sex hormone binding globulin (SHBG) and testosterone in adult male. METHODS: Cross-sectional study was conducted in three villages of Tongxu county including high fluoride group (HFG), defluoridation project group (DFPG) and control group (CG) based on the fluoride concentration in drinking water. Adult male who were born and raised in the village and aged 18 - 50 years old were recruited using cluster sampling. Fasting blood and morning urine samples were collected. The fluoride levels in drinking water and urine were detected by fluoride-ion selective electrode method. Serum SHBG level was determined using enzyme-linked immunosorbent assay (ELISA). The chemical luminescence immune analysis method was used to detect serum testosterone content. RESULTS: Serum SHBG level was 47.85 nmol/L in CG, 31.37 nmol/L in DFPG and 24.52 nmol/L in HFG respectively. There were significant difference among of three groups (P < 0.05). Serum testosterone level was 3.69 ng/ml in CG, 4.61 ng/ml in DFPG and 4.83 ng/ml in HFG respectively. Serum testosterone level in HFG was significantly higher than that in CG (P < 0.05). Serum SHBG level in HFG has positive correlation with serum testosterone (r = 0.230, P = 0.049), which has not been observed in DFPG and CG. CONCLUSIONS: Long-time fluorine exposure may affect serum SHBG and testosterone level in adult male.

PARM-1 promotes cardiomyogenic differentiation through regulating the BMP/Smad signaling pathway.

PARM-1, prostatic androgen repressed message-1, is an endoplasmic reticulum (ER) molecule that is involved in ER stress-induced apoptosis in cardiomyocytes. In this study, we assessed whether PARM-1 plays a role in the differentiation of stem cells into cardiomyocytes. While PARM-1 was not expressed in undifferentiated P19CL6 embryonic carcinoma cells, PARM-1 expression was induced during cardiomyogenic differentiation. This expression followed expression of mesodermal markers, and preceded expression of cardiac transcription factors. PARM-1 overexpression did not alter the expression of undifferentiated markers and the proliferative property in undifferentiated P19CL6 cells. Expression of cardiac transcription factors during cardiomyogenesis was markedly enhanced by overexpression of PARM-1, while expression of mesodermal markers was not altered, suggesting that PARM-1 is involved in the differentiation from the mesodermal lineage to cardiomyocytes. Furthermore, overexpression of PARM-1 induced BMP2 mRNA expression in undifferentiated P19CL6 cells and enhanced both BMP2 and BMP4 mRNA expression in the early phase of cardiomyogenesis. PARM-1 overexpression also enhanced phosphorylation of Smads1/5/8. Thus, PARM-1 plays an important role in the cardiomyogenic differentiation of P19CL6 cells through regulating BMP/Smad signaling pathways, demonstrating a novel role of PARM-1 in the cardiomyogenic differentiation of stem cells.