Bisphenol AF Induces Prostatic Dorsal Lobe Hyperplasia in Rats through Activation of the NF-κB Signaling Pathway.

Bisphenol AF (BPAF) represents a common environmental estrogenic compound renowned for its capacity to induce endocrine disruptions. Notably, BPAF exhibits an enhanced binding affinity to estrogen receptors, which may have more potent estrogenic activity compared with its precursor bisphenol A (BPA). Notwithstanding, the existing studies on BPAF-induced prostate toxicity remain limited, with related toxicological research residing in the preliminary stage. Our previous studies have confirmed the role of BPAF in the induction of ventral prostatic hyperplasia, but its role in the dorsal lobe is not clear. In this study, BPAF (10, 90 µg/kg) and the inhibitor of nuclear transcription factor-κB (NF-κB), pyrrolidinedithiocarbamate (PDTC, 100 mg/kg), were administered intragastrically in rats for four weeks. Through comprehensive anatomical and pathological observations, as well as the assessment of PCNA over-expression, we asserted that BPAF at lower doses may foster dorsal prostatic hyperplasia in rats. The results of IHC and ELISA indicated that BPAF induced hyperplastic responses in the dorsal lobe of the prostate by interfering with a series of biomarkers in NF-κB signaling pathways, containing NF-κB p65, COX-2, TNF-α, and EGFR. These findings confirm the toxic effect of BPAF on prostate health and emphasize the potential corresponding mechanisms.

The Antiproliferative and Proapoptotic Effects of Cucurbitacin B on BPH-1 Cells via the p53/MDM2 Axis.

Cucurbitacin B (Cu B), a triterpenoid compound, has anti-inflammatory and antioxidant activities. Most studies only focus on the hepatoprotective activity of Cu B, and little effort has been geared toward exploring the effect of Cu B on the prostate. Our study identified that Cu B inhibited the proliferation of the benign prostatic hyperplasia epithelial cell line (BPH-1). At the molecular level, Cu B upregulated MDM2 and thrombospondin 1 (THBS1) mRNA levels. Immunocytochemistry results revealed that the protein expressions of p53 and MDM2 were upregulated in BPH-1 cells. Furthermore, Cu B upregulated THBS1 expression and downregulated COX-2 expression in the BPH-1 cell supernatant. Altogether, Cu B may inhibit prostate cell proliferation by activating the p53/MDM2 signaling cascade and downregulating the COX-2 expression.

Bis-molybdopterin guanine dinucleotide modulates hemolysin expression under anaerobiosis and contributes to fitness in vivo in uropathogenic Escherichia coli.

Uropathogenic Escherichia coli (UPEC) is the primary causative agent of urinary tract infections (UTIs). Successful urinary tract colonization requires appropriate expression of virulence factors in response to host environmental cues, such as limited oxygen and iron availability. Hemolysin is a pore-forming toxin, and its expression correlates with the severity of UPEC infection. Previously, we showed that hemolysin expression is enhanced under anaerobic conditions; however, the genetic basis and regulatory mechanisms involved remain undefined. Here, a transposon-based forward screen identified bis-molybdopterin guanine dinucleotide cofactor (bis-MGD) biosynthesis as an important factor for a full transcription of hemolysin under anaerobiosis but not under aerobiosis. bis-MGD positively influences hemolysin transcription via c3566-c3568, an operon immediately upstream of and cotranscribed with hlyCABD. Furthermore, suppressor mutation analysis identified the nitrogen regulator NtrC as a direct repressor of c3566-c3568-hlyCABD expression, and intact bis-MGD biosynthesis downregulated ntrC expression, thus at least partially explaining the positive role of bis-MGD in modulating hemolysin expression. Finally, bis-MGD is involved in hemolysin-mediated uroepithelial cell death and contributes to the competitive fitness of UPEC in a murine model of UTI. Collectively, our data establish that bis-MGD biosynthesis plays a crucial role in UPEC fitness in vivo, thus providing a potential target for combatting UTIs.

Bisphenol A exposure triggers the malignant transformation of prostatic hyperplasia in beagle dogs via cfa-miR-204/KRAS axis.

The prostatic toxicity of bisphenol A (BPA) exposure is mainly associated with hormonal disturbances, thus interfering with multiple signal pathways and increasing the susceptibility to prostatic lesions. This study concentrates predominantly on the potential effect and mechanisms of low-dose BPA exposure on prostates in adult beagle dogs. The dogs were orally given BPA (2, 6, 18 µg/kg/day) and vehicle for 8 weeks, followed by blood collection and dissection. The ascended organ coefficient and volume of prostates, thickened epithelium, as well as histopathological observation have manifested that BPA exposure could trigger the aberrant prostatic hyperplasia in beagle dogs. Hormone level detection revealed that the ratios of estradiol (E2) to testosterone (T) (E2/T) and prolactin (PRL) to T (PRL/T) were up-regulated in the serum from BPA group. Based on microRNA (miRNA) microarray screening and functional enrichment analysis, BPA might facilitate the progression of prostate tumorigenesis in beagle dogs via cfa-miR-204 and its downstream target KRAS oncogene. Subsequently, the overexpression of KRAS, CDKN1A, MAPK1, VEGFA, BCL2 and PTGS2 was validated. These findings provide a series of underlying targets for preventing the initiation and metastasis of BPA-induced prostatic hyperplasia and tumorigenesis, while the regulatory relationship headed with KRAS requires further investigation.

Individual and Combined Effect of Bisphenol A and Bisphenol AF on Prostate Cell Proliferation through NF-κB Signaling Pathway.

The ubiquitous environmental endocrine disruptor bisphenol A (BPA) can induce prostatic dysfunction. However, to date, studies have focused little on the perturbations of prostate health initiated by the BPA derivative bisphenol AF (BPAF) and co-exposure to bisphenol compounds. An in vivo study orally administrated male rats with BPA (10, 90 µg/kg), BPAF (10, 90 µg/kg) and the inhibitor of nuclear transcription factor-κB (NF-κB), pyrrolidinedithiocarbamate (PDTC, 100 mg/kg). Based on the anatomical analysis, pathological observations and PCNA over-expression, we considered that low-dose BPA and BPAF facilitated ventral prostatic hyperplasia in rats. The results of IHC and ELISA mirrored the regulation of NF-κB p65, COX-2, TNF-α and EGFR in BPA- and BPAF-induced prostatic toxicity. An in vitro study found that the additive effect of combined exposure to BPA (10 nM) and BPAF (10 nM) could cause an elevation in the proliferation of and a reduction in the apoptosis level of human prostate stromal cells (WPMY-1) and fibroblasts (HPrF). Meanwhile, the underlying biomarkers of the NF-κB signaling pathway also involved the abnormal proliferative progression of prostate cells. The findings recapitulated the induction of BPAF exposure and co-treatment with BPA and BPAF on prostatic hyperplasia and emphasized the modulation of the NF-κB signaling pathway.

BPA-induced prostatic hyperplasia in vitro is correlated with the unbalanced gene expression of AR and ER in the epithelium and stroma.

As a typical environmental endocrine disruptor (EED), bisphenol A (BPA) can induce pathological hyperplasia of the prostatic epithelium and stroma. This study concentrates mainly on the effect and underlying mechanisms of BPA on prostatic hyperplasia, which is based on the culture of primary human prostate epithelial cells (HPEpiC) and human prostate fibroblasts (HPrF). In an effect to screen the optimal pro-survival BPA levels, HPEpiC and HPrF were, respectively, exposed to concentration gradients of BPA (10-12 M-10-4 M) solution diluted with two corresponding medium and incubated for 72 h at 37°C. CCK-8 assay showed that 10-9 M-10-5 M BPA could facilitate the proliferation of HPEpiC, while similar proliferative effect of HPrF only needed 10-11 M-10-7 M BPA. HPrF were more sensitive to BPA than HPEpiC. The qualification of PCNA gene expression measured using quantitative real-time polymerase chain reaction (qRT-PCR) also mirrored the BPA-induced cell proliferation. Additionally, our results considered that androgen receptor (AR), estrogen receptor (ERα, ERß), and NFKB1 gene expressions exhibited up-regulation in HPEpiC treated with 10-9 M BPA for 72 h. However, in HPrF, the identical BPA treatment could activate ERα, ERß, and NFKB1 gene expressions and down-regulated the expression of AR levels. It is further confirmed that low-dose BPA can indeed promote the proliferation of human prostate cells in vitro, and the mechanisms of BPA for prostatic epithelial and stromal hyperplasia may not be consistent.

PD-L1 and MRN synergy in platinum-based chemoresistance of head and neck squamous cell carcinoma.

BACKGROUND: We have been investigating the molecular mechanisms of cisplatin-induced chemoresistance in head and neck squamous cell carcinoma (HNSCC). Based on our previous findings, the present study investigates how the Mre11, Rad50, and NBS1 (MRN) DNA repair complex interacts at the molecular level with the programmed cell death ligand 1 (PD-L1) in cisplatin-induced chemoresistance. METHODS: Human HNSCC cell lines were used to determine the role played by PD-L1 in cisplatin resistance. Initial experiments investigated PD-L1 expression levels in cells exposed to cisplatin and whether PD-L1 interacts directly with the MRN complex. Finally, in vitro studies and in vivo experiments on BALB/c nu/nu mice were performed to determine whether interference of PD-L1 or NBS1 synthesis modulated cisplatin resistance. RESULTS: Exposure to cisplatin resulted in PD-L1 being upregulated in the chemoresistant but not the chemosensitive cell line. Subsequent co-immunoprecipitation studies demonstrated that PD-L1 associates with NBS1. In addition, we found that the knockdown of either PD-L1 or NBS1 re-sensitised the chemoresistant cell line to cisplatin. Finally, but perhaps most importantly, synergy was observed when both PD-L1 and NBS1 were knocked down making the formerly chemoresistant strain highly cisplatin sensitive. CONCLUSIONS: PD-L1 plays a pivotal role in cisplatin resistance in chemoresistant human HNSCC cell lines.

Feature Point Registration Model of Farmland Surface and Its Application Based on a Monocular Camera.

In this study, an image registration algorithm was applied to calculate the rotation angle of objects when matching images. Some commonly used image feature detection algorithms such as features from accelerated segment test (FAST), speeded up robust features (SURF) and maximally stable extremal regions (MSER) algorithms were chosen as feature extraction components. Comparing the running time and accuracy, the image registration algorithm based on SURF has better performance than the other algorithms. Accurately obtaining the roll angle is one of the key technologies to improve the positioning accuracy and operation quality of agricultural equipment. To acquire the roll angle of agriculture machinery, a roll angle acquisition model based on the image registration algorithm was built. Then, the performance of the model with a monocular camera was tested in the field. The field test showed that the average error of the rolling angle was 0.61°, while the minimum error was 0.08°. The field test indicated that the model could accurately obtain the attitude change trend of agricultural machinery when it was working in irregular farmlands. The model described in this paper could provide a foundation for agricultural equipment navigation and autonomous driving.

Aberrant promoter methylation reduced the expression of protocadherin 17 in nasopharyngeal cancer.

This study aimed to explore the underlying mechanism of protocadherin 17 (PCDH17) downregulated in nasopharyngeal cancer (NPC). NPC tumor and adjacent tissue samples were collected from NPC patients who received therapy in the Chinese PLA General Hospital. Meanwhile, a normal epithelial cell lines NP96 and 6 NPC and cell lines C666-1, CEN1, CEN2, HNE1, HEN2, and HONE1 were prepared. Then, the expression level of PCDH17 and the methylation level of PCDH17 promoter in both tissues samples and cell lines were determined using the PCR method. Moreover, PCDH17 was overexpressed in CNE2 and HONE1 using Lipo2000. Following this, the proliferation and apoptosis of CNE2 and HONE1 were assessed using MTT and flow cytometry. The expression of PCDH17 was significantly downregulated in NPC tissues compared with the adjacent tissues as well as in the NPC cell lines compared with the normal NP96 cells. Overexpressed PCDH17 could significantly inhibit the proliferation of CNE2 and HONE1 cells but obviously promote the apoptosis of these two cell lines. Aberrant hypermethylation in the promoter might be the explanation of PCDH17 downregulated in PCDH17 and promoted the development of NPC.

Detection and genetic characterization of porcine pegivirus from pigs in China.

Porcine pegiviruses (PPgV) have been first discovered in serum samples from domestic pigs in Germany in 2016 and then in the USA in 2018. To date, there is no documentation with respect to the presence of PPgVs in domestic pigs in China. Herein, we attempted to determine the presence and prevalence of PPgV in China and its genetic characterization. In this study, 469 sera were tested and 34 (7.25%) were positive for PPgV. An ascending trend of the positive rate for PPgV was observed from suckling piglets (1.61%) to nursing piglets (1.85%), finishing pigs (6.56%), and sows (11.34%). The complete genome sequence of a representative strain of PPgV, PPgV_GDCH2017, and the complete E2 gene of 17 PPgV isolates discovered in this study was determined. Sequence analysis indicated that PPgV_GDCH2017 was highly related to other PPgVs with nucleotide and amino acid identities ranging from 87.3 to 97.4% and 94.6-99.3%, respectively, in the complete coding region. Phylogenetic analyses demonstrated that the PPgV_GDCH2017 discovered in this study was closely related to the PPgVs from the USA and clustered in the same genus with pegiviruses from other hosts. The topology of the phylogenetic tree based on the complete E2 gene was consistent with that based on the complete genome of PPgV. Further studies on pathogenicity and pathogenesis of PPgVs are needed.

Oral exposure to low-dose bisphenol A induces hyperplasia of dorsolateral prostate and upregulates EGFR expression in adult Sprague-Dawley rats.

Prostate is sensitive to endocrine hormone level, and the synergetic effect of estrogen and androgen is critical in prostate growth. The change of signal pathways caused by the imbalance of estrogen and androgen might function in the occurrence of prostate diseases. As a well-known endocrine disruptor compound, bisphenol A (BPA) can disturb the normal function of endocrine hormone and affect prostate development. This study aims to investigate effects of BPA on the dorsolateral prostate (DLP) and the related gene expression of the tissue in adult Sprague-Dawley (SD) rats and to explore the mechanism for the effect of low-dose BPA on DLP hyperplasia. Three-month-old male SD rats were treated with BPA (10.0, 30.0, or 90.0 µg (kg.day)-1, gavage) or vehicle (gavage) for 4 weeks. BPA significantly increased the DLP weight, the DLP organ coefficient, and the prostate epithelium height (p < 0.01) of rats dose-dependently. Microarray analysis and quantitative real-time polymerase chain reaction showed that BPA significantly upregulated the transcriptional levels of some genes, including pituitary tumor transforming gene 1, epidermal growth factor, Sh3kbp1, and Pcna. Furthermore, the expression of PCNA (p < 0.01), androgen receptor (p < 0.01), and EGF receptor (EGFR) (p < 0.001) in DLP was increased significantly by BPA treatment, and the expression of estrogen receptor alpha was also upregulated. The findings evidenced that low-dose BPA could induce DLP hyperplasia in adult rats, and the upregulated EGF/EGFR pathway that was responsive to estrogen and androgen might play an essential role in the DLP hyperplasia induced by low-dose BPA.

A Novel Method for Soil Organic Matter Determination by Using an Artificial Olfactory System.

Soil organic matter (SOM) is a major indicator of soil fertility and nutrients. In this study, a soil organic matter measuring method based on an artificial olfactory system (AOS) was designed. An array composed of 10 identical gas sensors controlled at different temperatures was used to collect soil gases. From the response curve of each sensor, four features were extracted (maximum value, mean differential coefficient value, response area value, and the transient value at the 20th second). Then, soil organic matter regression prediction models were built based on back-propagation neural network (BPNN), support vector regression (SVR), and partial least squares regression (PLSR). The prediction performance of each model was evaluated using the coefficient of determination (R2), root-mean-square error (RMSE), and the ratio of performance to deviation (RPD). It was found that the R2 values between prediction (from BPNN, SVR, and PLSR) and observation were 0.880, 0.895, and 0.808. RMSEs were 14.916, 14.094, and 18.890, and RPDs were 2.837, 3.003, and 2.240, respectively. SVR had higher prediction ability than BPNN and PLSR and can be used to accurately predict organic matter contents. Thus, our findings offer brand new methods for predicting SOM.

A simple and rapid identification method for newly emerged porcine Deltacoronavirus with loop-mediated isothermal amplification.

BACKGROUND: Porcine Deltacoronavirus (PDCoV) is a newly emerged enteropathogenic coronavirus that causes diarrhea and mortality in neonatal piglets. PDCoV has spread to many countries around the world, leading to significant economic losses in the pork industry. Therefore, a rapid and sensitive method for detection of PDCoV in clinical samples is urgently needed. RESULTS: In this study, we developed a single-tube one-step reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay specific for nucleocapsid gene to diagnose and monitor PDCoV infections. The detection limit of RT-LAMP assay was 1 × 101 copies of PDCoV, which was approximately 100-fold more sensitive than gel-based one-step reverse transcription polymerase chain reaction (RT-PCR). This assay could specifically amplify PDCoV and had no cross amplification with porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), porcine kobuvirus (PKoV), porcine astrovirus (PAstV), porcine reproductive and respiratory syndrome virus (PRRSV), classic swine fever virus (CSFV), and porcine circovirus type 2 (PCV2). By screening a panel of clinical specimens (N = 192), this method presented a similar sensitivity with nested RT-PCR and was 1-2 log more sensitive than conventional RT-PCR in detection of PDCoV. CONCLUSIONS: The RT-LAMP assay established in this study is a potentially valuable tool, especially in low-resource laboratories and filed settings, for a rapid diagnosis, surveillance, and molecular epidemiology investigation of PDCoV infections. To the best of our knowledge, this is the first work for detection of newly emerged PDCoV with LAMP technology.

Oral administration of low-dose bisphenol A promotes proliferation of ventral prostate and upregulates prostaglandin D2 synthase expression in adult rats.

This study aims to assess the effect of low oral dose of bisphenol A (BPA) on proliferation of ventral prostate (VP) and expression of related genes in adult rats. Three-month-old male Sprague Dawley rats were treated daily with BPA (10, 30, or 90 µg/kg, per os), 17ß-estradiol (E2, 10.0 µg/kg, subcutaneously), or vehicle for 4 weeks. Treatment with 10 µg/kg BPA resulted in increased animal weight and VP epithelial height compared with the controls ( p < 0.01), while such effects were less pronounced in higher BPA doses. Treatment with E2 showed opposite effects, with significantly decreased animal weight and VP epithelial height ( p < 0.01). Interestingly, BPA increased serum E2 and reduced testosterone levels and significantly increased the estrogen to androgen ratio ( p < 0.05). In addition, BPA slightly increased dihydrotestosterone (DHT) levels. Immunohistochemistry data showed that BPA significantly upregulated proliferating cell nuclear antigen expression ( p < 0.01). Furthermore, microarray and reverse transcription polymerase chain reaction analyses showed that BPA induced upregulation of prostaglandin D2 synthase ( Ptgds), Fas, Pbef1, and complement factor B ( Cfb)as well as downregulation of Pttg1 and Fabp4 in the VP. These results indicated that environmental exposure to low doses of BPA may induce proliferation of VP in adult rats by increasing the estrogen to androgen ratio and upregulating expression of Ptgds to promote production of DHT.

Confounding Effect in Clinical Research of Otolaryngology and Its Control.

Confounding effect is a critical issue in clinical research of otolaryngology because it can distort the research's conclusion. In this review, we introduce the definition of confounding effect, the methods of verifying and controlling the effect. Confounding effect can be prevented by research's design, and adjusted by data analysis. Clinicians would be aware and cautious about confounding effect in their research. They would be able to set up a research's design in which appropriate methods have been applied to prevent this effect.They would know how to adjust confounding effect after data collection. It is important to remember that sometimes it is impossible to eliminate confounding effect completely, and statistical method is not a master key. Solid research knowledge and critical thinking of our brain are the most important in controlling confounding effect.

Genetic Effects on Sensorineural Hearing Loss and Evidence-based Treatment for Sensorineural Hearing Loss.

In this article, the mechanism of inheritance behind inherited hearing loss and genetic susceptibility in noise-induced hearing loss are reviewed. Conventional treatments for sensorineural hearing loss (SNHL), i.e. hearing aid and cochlear implant, are effective for some cases, but not without limitations. For example, they provide little benefit for patients of profound SNHL or neural hearing loss, especially when the hearing loss is in poor dynamic range and with low frequency resolution. We emphasize the most recent evidence-based treatment in this field, which includes gene therapy and allotransplantation of stem cells. Their promising results have shown that they might be options of treatment for profound SNHL and neural hearing loss. Although some treatments are still at the experimental stage, it is helpful to be aware of the novel therapies and endeavour to explore the feasibility of their clinical application.

[Categories and characteristics of BPH drug evaluation models: a comparative study].

Benign prostatic hyperplasia (BPH) is a worldwide common disease in men over 50 years old, and the exact cause of BPH remains largely unknown. In order to elucidate its pathogenesis and screen effective drugs for the treatment of BPH, many BPH models have been developed at home and abroad. This article presents a comprehensive analysis of the categories and characteristics of BPH drug evaluation models, highlighting the application value of each model, to provide a theoretical basis for the development of BPH drugs.

Protection of guinea pigs by vaccination with a recombinant swinepox virus co-expressing HA1 genes of swine H1N1 and H3N2 influenza viruses.

Swine influenza (SI) is an acute respiratory infectious disease of swine caused by swine influenza virus (SIV). SIV is not only an important respiratory pathogen in pigs but also a potent threat to human health. Here, we report the construction of a recombinant swinepox virus (rSPV/H3-2A-H1) co-expressing hemagglutinin (HA1) of SIV subtypes H1N1 and H3N2. Immune responses and protection efficacy of the rSPV/H3-2A-H1 were evaluated in guinea pigs. Inoculation of rSPV/H3-2A-H1 yielded neutralizing antibodies against SIV H1N1 and H3N2. The IFN-γ and IL-4 concentrations in the supernatant of lymphocytes stimulated with purified SIV HA1 antigen were significantly higher (P < 0.01) than those of the control groups. Complete protection of guinea pigs against SIV H1N1 or H3N2 challenge was observed. No SIV shedding was detected from guinea pigs vaccinated with rSPV/H3-2A-H1 after challenge. Most importantly, the guinea pigs immunized with rSPV/H3-2A-H1 did not show gross and micrographic lung lesions. However, the control guinea pigs experienced distinct gross and micrographic lung lesions at 7 days post-challenge. Our data suggest that the recombinant swinepox virus encoding HA1 of SIV H1N1 and H3N2 might serve as a promising candidate vaccine for protection against SIV H1N1 and H3N2 infections.

Nitrogen-doped Ti3C2 MXene quantum dots as an effective FRET ratio fluorometric probe for sensitive detection of Cu2+ and D-PA.

In this work, a ratiometric fluorescence sensing platform was established to detect Cu2+ and D-PA (d-penicillamine) based on nitrogen-doped Ti3C2 MXene quantum dots (N-MODs) that was prepared via a simple hydrothermal method and exhibited strong fluorescent and photoluminescence performance as well as excellent stability. Since the oxidation reaction between o-phenylenediamine (OPD) and Cu2+ induced the formation of 2,3-diaminophenazine (ox-OPD) which not only can emerge an emission peak at 570 nm, but also inhibit the fluorescence intensity of N-MQDs at 450 nm, a ratiometric reverse fluorescence sensor via fluorescence resonance energy transfer (FRET) was designed to sensitively detect Cu2+, where N-MQDs acted as energy donor and ox-OPD as energy acceptor. More importantly, another considerably interesting phenomenon was that their catalytic oxidation reaction can be restrained in the presence of D-PA because of the coordination of Cu2+ with D-PA, further triggering the obvious changes in ratio fluorescent signal and color, thus a ratiometric fluorescent sensor of determining D-PA was proposed also in this work. After optimizing various conditions, the ratiometric sensing platform showed rather low detection limits for Cu2+ (3.0 nM) and D-PA (0.115 µM), coupled with excellent sensitivity and stability.

Oral exposure to DEHP may stimulate prostatic hyperplasia associated with upregulation of COX-2 and L-PGDS expressions in male adult rats.

Di-(2-ethylhexyl) phthalate (DEHP), a typical environmental endocrine disruptor (EED), can disrupt estrogen and androgen secretion and metabolism process, thus inducing dysfunctional reproduction such as impaired gonadal development and spermatogenesis disorder. Prostaglandin synthases (PGS) catalyze various prostaglandins biosynthesis, involved in inflammatory cascade and tumorigenesis. Yet, little is known about how PGS may impact prostatic hyperplasia development and progression. This study concentrates predominantly on the potential prostatic toxicity of DEHP exposure and the mediating role of PGS. In vivo study, adult male rats were administered via oral gavage 30 µg/kg/d, 90 µg/kg/d, 270 µg/kg/d, 810 µg/kg/d DEHP or vehicle for four weeks. The results elucidated that low-dose DEHP may cause the proliferation of the prostate with an increased PCNA/TUNEL ratio. Given the importance of estrogens and androgens in prostatic hyperplasia, our first objective was to evaluate the levels of sex hormones. DEHP improved the ratio of estradiol (E2)/testosterone (T) in a dose-dependent manner and upregulated estrogen receptor alpha (ERα) and androgen receptor (AR) expressions. Prostaglandin synthases, including cyclooxygenase-2 (COX-2) and lipocalin-type prostaglandin D synthase (L-PGDS), were significantly upregulated in the ventral prostate. COX-2 and L-PGDS might mediate the tendency of prostatic hyperplasia induced by low-dose DEHP through estradiol/androgen regulation and imbalance between proliferation and apoptosis in vivo. These findings provide the first evidence that prostaglandin synthases contribute to the tendency toward benign prostatic hyperplasia induced by DEHP. Further investigations will have to be performed to facilitate an improved understanding of the role of prostaglandin synthases in DEHP-induced prostatic lesions.