Relationship between hand-foot skin reaction and external force on patients with hepatocellular carcinoma: A cohort study.

PURPOSE: Hand-foot skin reaction (HFSR), a side effect of tyrosine kinase inhibitor (TKI) treatment, makes it difficult to walk and perform daily activities because of pain in the limbs. HFSR occurs predominantly in the sites where external forces (pressure and shear stress) are applied. This study aimed to determine whether pressure or shear stress induces the occurrence of HFSR. METHODS: This cohort study was conducted in patients who received TKI treatment for hepatocellular carcinoma. The external forces applied to the sole of the patients' foot while walking was measured, and its association with the occurrence of HFSR was examined. The degree of HFSR was assessed by the patient's response during the examination and by photographs of their feet. The patients' feet were divided into low (grade <2) or high (grade ≥2) HFSR foot group, and the differences in external forces between the groups were analyzed using t-test and Cox hazard analysis. RESULTS: Analysis of the feet of 55 study participants (n = 110) showed no significant difference between the groups on t-test (p ≥ 0.05), however, Cox hazard analysis showed an increased risk of HFSR with higher peak shear stress values at the fifth metatarsal head (hazard ratio = 1.01, p = 0.047; 95% confidence interval = 1.00-1.02). CONCLUSION: Shear stress is possibly related to HFSR occurrence. Nurses should assess whether patients' shoes fit their feet before initiating TKI treatment. They should instruct patients to wear shoes that are fit of both diameter and width for their feet.

Impact of nurse-assisted patient turning at different sleep stages on the quality of subsequent sleep.

BACKGROUND: Nursing care performed during sleep, including nurse-assisted patient turning, is one of the factors that deteriorates sleep quality but is necessary for pressure ulcer prevention. Thus, it is important to determine when nurseassisted patient turning has the least impact on sleep quality. AIM: The aim of this study was to clarify the impact of nurseassisted patient turning at different sleep stages and to determine the optimal timing of this aspect during sleep. METHODS: The experiment, which consisted of healthy men in their 20s and 30s, was performed over four successive nights per subject. The first night was dedicated to environment adaptation, and the 2nd to the 4th nights were randomly assigned for shallow sleep intervention, deep sleep intervention, and non-intervention. On the intervention day, nurse-assisted patient turning was conducted twice. Overnight sleep conditions were measured by polysomnography (PSG). The PSG waveform transmitted to a tablet was analyzed in real time to determine the stage of sleep. The patient was turned when he entered the planned stage of sleep. RESULTS: The study analyzed fourteen (14) subjects. Shallow sleep time, deep sleep time, and sleep resumption time after nurse-assisted patient turning were compared among the three groups of non-intervention day, shallow sleep intervention day and deep sleep intervention day. There was no significant difference in the shallow and deep sleep time among the three groups. However, sleep resumption time after nurse-assisted patient turning was significantly shorter on the deep sleep intervention day than on the shallow sleep intervention day (p = textbf 0.033). CONCLUSIONS: This study has novelty in examining the impact of nurse-assisted patient turning performed at different sleep stages on subsequent sleep using objective indicators. The study suggested that a deep sleep state is the optimal timing of nurseassisted patient turning due to the short time to sleep resumption.

Examination of the Effect of Suitable Size of Shoes under the Second Metatarsal Head and Width of Shoes under the Fifth Metatarsal Head for the Prevention of Callus Formation in Healthy Young Women.

Excessive pressure and shear stress while walking cause a risk of callus formation, which eventually causes foot ulcers in patients with diabetes mellitus. Callus under the second metatarsal head (MTH) has been associated with increased shear stress/pressure ratios (SPR). Callus under the fifth MTH has been associated with increased peak shear stress (PSS). The purpose of this study is to examine whether the effect of the suitable size and width of shoes prevents diabetic foot ulcers under the second and fifth MTH. We measured the pressure and shear stress by testing three kinds of sizes and two types of width of shoes. Significant difference was not observed in the SPR under the second MTH among different sizes of shoes. However, the pressure and shear stress were significantly lower when putting on shoes of fit size compared with larger sizes. The PSS under the fifth MTH was significantly smaller when putting on shoes of fit width compared with those of narrow width. Wearing shoes of fit size and width has the potential to prevent callus formation by reducing the pressure and shear stress constituting SPR under the second MTH and PSS under the fifth MTH.

The external force associated with callus formation under the first metatarsal head is reduced by wearing rocker sole shoes.

INTRODUCTION: Callus is one of the main causes of diabetic foot ulcers. Therefore, preventing callus formation is very important. In a previous study, it was clarified that callus formation under the first metatarsal head (MTH) is associated with high shear stress time integral/pressure time integral (SPR-i). another study, it was clarified that rocker sole shoes are effective in reducing peak pressure under the first MTH. Therefore, we hypothesized that rocker sole shoes reduce SPR-i under the first MTH. This study aimed to clarify the effect of rocker sole shoes for external forces and leg motions in comparison with that of the normal sole shoes. METHODS: In-shoe external forces and leg motions were measured during walking wearing the normal sole shoes or the rocker sole shoes in healthy participants. As the external forces, the peak plantar pressure (PP), pressure time integral (PI), peak shear stress (PSS), and shear stress integral (SSI) of each gait cycle were calculated. Additionally, shear stress-pressure ratios (SPR) were calculated by dividing shear stress by pressure; concretely, peak values (SPR-p) and time integral values (SPR-i). As the leg motion, hip and knee joint motions were analyzed for the axis of flexion- extension. Three axes of ankle joint motion (inversion-eversion, plantar flexion-dorsiflexion, and adduction-abduction) were analyzed. RESULTS AND DISCUSSION: Six participants attended, and twelve feet were analyzed. When wearing the rocker sole shoes, the SPR-i under the first MTH was significantly smaller than when wearing the normal sole shoes. The SPR-i higher than 0.60 is associated with callus formation under the first MTH. In three of five feet with callus, SPR-i exceeded 0.60 in the normal sole shoes. The SPR-i of all three feet became smaller than 0.60 when wearing the rocker sole shoes. Although the knee (flexion-extension) and ankle (plantar flexion-dorsiflexion) joint motion became smaller when wearing the rocker sole shoes, there was no significant difference in walking speed. It is considered that propulsion was maintained by the push-off support provided by rocker sole shoes. CONCLUSION: It was suggested that rocker sole shoes are effective preventing callus formation under the first MTH.

Levels of formaldehyde vapor released from embalmed cadavers in each dissection stage.

Formaldehyde (FA) is an aldehyde used in antiseptics and adhesives. The World Health Organization (WHO) and other institutes have linked FA to sick building syndrome and allergic diseases. Recent studies have reported that cadavers embalmed using formalin and ethanol-based preservative solutions release FA vapor during dissection and that FA vapor may adversely affect students and lecturers in gross anatomy laboratories. However, few details have been reported correlating dissection stage with increased FA vapor release. In this study, we evaluated the vapor level of FA released in each dissection stage. Six cadavers for which consent was given for use in anatomy research and education were examined in this study. Using an active sampling method, FA vapor was collected above the thoracoabdominal region of each dissected cadaver. FA was eluted from each sampler using acetonitrile and analyzed by high-performance liquid chromatography. Our data show that FA levels significantly increase after skin incision and that the vapor level of FA released differs between male and female cadavers. We also found that subcutaneous adipose tissues of the thoracoabdominal-region release FA vapor and that female cadavers release significantly higher levels of FA per kilogram of subcutaneous adipose tissue than do male cadavers. Based on these data, we propose the methods be developed to prevent exposure to FA vapors released from cadavers.

Neonatal exposure to diethylstilbestrol causes granulomatous orchitis via epididymal inflammation.

Diethylstilbestrol (DES), an endocrine-disrupting chemical, is an infamous artificial estrogenic compound. Although neonatal exposure to DES has been shown to result in inflammation of the male reproductive system, it has not, to our knowledge, been reported to induce testicular inflammation. Here we report that neonatal exposure to DES caused granulomatous orchitis with spermatogenic disturbance in 4 of 17 ICR male mice at 12 weeks of age. In the animals with spermatogenic disturbance, we observed either seminiferous tubules containing only cells with Sertoli cell features (likely Sertoli cell syndrome), or tubule cells in maturation arrest that contained only spermatogonia and/or spermatocytes. Following neonatal DES exposure, 5-week-old mice exhibited inflammation in cauda epididymis; by 8 weeks, the inflammation had spread to all segments of epididymis but not the testis; by 12 weeks, inflammation of the epididymis was observed in all mice. These data indicated that cauda epididymis has increased sensitivity to neonatal DES exposure compared to other segments of epididymis and testis. The data also implied that neonatal DES exposure-induced inflammation in cauda epididymis extended gradually to the testis via corpus and caput during development.

Changes in expression levels of oxidative stress-related genes in mouse epididymides by neonatal exposure to low-dose decabromodiphenyl ether.

Decabromodiphenyl ether (decaBDE), one of the polybrominated diphenyl ethers (PBDEs), is the most well-known flame retardant and is used worldwide. In a previous study, we identified adverse effects of neonatal decaBDE exposure on mouse epididymides, such as decreased epididymal weight. On the other hand, neonatal exposure to diethylstilbestrol (DES), an artificial estrogenic compound, also causes several adverse effects on epididymides. DES exposure results in decreased epididymal weight, morphological abnormalities, and permanent alterations in the expression levels of several genes. The molecular mechanisms underlying the harmful effects of decaBDE exposure remain unclear. Many studies have reported that PBDEs have estrogenic activity, which may contribute to the induction of the adverse effects of decaBDE exposure. We aimed to examine the effects of neonatal decaBDE exposure on epididymides. Our data showed that (1) no histological change was observed on epididymal tissues from neonatal decaBDE exposure, unlike the effect of DES, (2) decaBDE exposure did not induce the alterations in gene expression observed with DES exposure; instead alterations in gene expression of certain oxidative stress-related genes were observed, and (3) the expression of ubiquitin C increased in decaBDE-exposed mouse epididymides. Our present data suggest the possibility that increased oxidative stress plays a role in the harmful effects observed in mouse epididymides after decaBDE-exposure.

Effects on the local immunity in the testis by exposure to di-(2-ethylhexyl) phthalate (DEHP) in mice.

Exposure to di-(2-ethylhexyl) phthalate (DEHP) has been reported to induce spermatogenic disturbance through oxidant stress and affect the immune system as an adjuvant. However, the effect of DEHP on the testicular immune microenvironment has not yet been investigated. In the present study, we examined the testicular immune microenvironment after exposure to doses of DEHP, previously identified as no-observed-adverse-effect levels. Adult male mice were administered food containing 0%, 0.01% or 0.1% DEHP and then testes were analyzed. The results showed that a slight but significant spermatogenic disturbance appeared in the 0.1% DEHP group but not in the 0.01% DEHP group at 8 weeks. It was also demonstrated that lymphocytes and F4/80- and MHC class II- positive cells were significantly increased with the elevation of IL-10 and IFN-γ mRNA expressions in the testes of not only the 0.1% DEHP group but also the 0.01% DEHP group at 8 weeks. Histochemical analyses involving horseradish peroxidase (HRP) as a tracer showed that a little blood-borne HRP had infiltrated into the lumen of a few seminiferous tubules beyond the blood-testis-barrier in both the 0.1% and 0.01% DEHP groups at 8 weeks. This indicates that a dose of DEHP that has little effects on spermatogenesis can change the testicular immune microenvironment with functional damage of the blood-testis barrier.

Cadmium exposure increases susceptibility to testicular autoimmunity in mice.

Cadmium, one of various environmental toxicants, is known to suppress systemic immunity and to injure the testicular capillary endothelia with resultant necrosis of testicular tissues in mice and rats treated with high doses. Recently, it also became evident that cadmium can affect the integrity of the blood-testis barrier (BTB), the endocrine function of Leydig cells, apoptosis of germ cells and systemic immunity, even on treatment with a low dose that does not induce spermatogenic disturbance. Experimental autoimmune orchitis (EAO), i.e., an organ-specific autoimmunity of the testis, can be induced by repeated immunization with testicular antigens, and its pathology is characterized by lymphocytic inflammation and spermatogenic disturbance. In the present study, we investigated the morphological and functional changes of testes in mice treated with a low dose of cadmium chloride (CdCl2 ) and also examined its toxicity as to susceptibility to EAO. The results showed that exposure to 3 mg CdCl2 kg(-1) body weight did not affect the spermatogenic state. However, the BTB at the tubuli recti and the rete testis, but not the seminiferous tubules, was slightly weakened, and intra-testicular mRNA expression of interleukin (IL)-6, tumor necrosis factor-α and IL-1ß was significantly increased by the CdCl2 treatment. Furthermore, immunization with testicular antigens after the CdCl2 exposure significantly augmented the EAO severity. Therefore, exposure to a low dose of CdCl2 induces no significant disturbance of spermatogenesis, however, it does change the immunological microcircumstances in the testis, resulting in increased susceptibility to testicular autoimmunity.

Anatomical study using cadavers for imaging of life-threatening complications in Le Fort III distraction.

BACKGROUND: Few reports describe devastating complications with conventional Le Fort III osteotomy; however, life-threatening complications have been reported occasionally with Le Fort III distraction. An anatomical study using cadaveric Le Fort III osteotomy models was performed to investigate the causes of untoward fractures that might induce devastating complications. METHODS: The study sample consisted of 30 cadavers (60 sides). Specimens were separated into six groups depending on whether osteotomy of the lateral maxillary wall from the inferior orbital fissure to the pterygomaxillary junction (procedure A) and separation of the pterygomaxillary junction (procedure B) were performed completely, incompletely, or not at all. All osteotomy and fracture lines including the skull base and orbit were examined by computed tomography and direct observation. The separation or fracture type of the pterygoid plate of the sphenoid bone was categorized into four groups: ideal separation, low-level fracture, high-level fracture, and others. The frequency of each type of pterygoid plate fracture between controls and each group was compared. RESULTS: High-level fractures occurred more frequently in groups with intact pterygomaxillary junctions. All specimens with untoward fractures of the sphenoid bone leading to the skull base or carotid canal accompanied high-level pterygoid fractures, occurring in groups without sufficient pterygomaxillary separation. An extraordinary orbital fracture was observed when neither procedure A nor procedure B was performed. CONCLUSIONS: Precise separation of the pterygomaxillary junction is primarily of importance for preventing devastating complications of Le Fort III osteotomy and Le Fort III distraction. Osteotomy of the lateral maxillary wall is also necessary to minimize this risk.

Postnatal exposure to low-dose decabromodiphenyl ether adversely affects mouse testes by increasing thyrosine phosphorylation level of cortactin.

Decabromodiphenyl ether (decaBDE) is a brominated flame retardant used in many commercial products such as televisions, computers, and textiles. Recent reports indicate that decaBDE adversely affects male reproductive organs in mice, but the underlying molecular mechanisms remain unknown. We hypothesized that decaBDE affects mouse testes by altering the expression and phosphorylation level of cortactin (CTTN), an F-actin-binding protein that is similar to flutamide, and we performed western blot analyses on testicular samples from mice subcutaneously injected with decaBDE (0.025, 0.25, and 2.5 mg/kg body weight/day) on postnatal days 1 to 5. Mice treated with low-dose decaBDE (0.025 mg/kg) showed reduced testicular weight, sperm count, elongated spermatid and Sertoli cell numbers, as well as induced Tyr phosphorylation of CTTN and reduced the expression level of p60 Src tyrosine kinase (SRC). Further, 0.25 and 2.5 mg/kg decaBDE-exposed groups produced an decrease the expression level of CTTN. High-dose decaBDE (2.5 mg/kg) showed increased abnormal germ cells, as well as induced Ser phosphorylation of CTTN and activated extracellular signal-regulated kinase (ERK1/2); however, high-dose decaBDE did not affect testicular weight and sperm count. These findings suggest that postnatal exposure to low-dose decaBDE inhibits mouse testicular development by increasing Tyr phosphorylation of CTTN, although different mechanisms may be involved depending on the dose of decaBDE.

Interpretation of multi-detector computed tomography images before dissection may allow detection of vascular anomalies: a postmortem study of anomalous origin of the right subclavian artery and the right vertebral artery.

The Graduate School of Medicine at Chiba University is planning to introduce computed tomography (CT) images of donated cadavers to the gross anatomy laboratory. Here we describe an anomaly of the right subclavian artery that was detected by interpretation of CT images prior to dissection. The anomaly was verified to be the right subclavian artery, as the last branch of the aortic arch, by subsequent dissection of the cadaver. We also identified an anomalous origin of the right vertebral artery by dissection. This anomaly was also visible on CT images, although it had not been recognized in the first interpretation of the CT images. Our results suggest that branching anomalies of arteries with a diameter of >1 cm are detectable on CT images even without the injection of contrast medium. We also discuss the utility of interpreting CT images prior to dissection as a means by which medical students can gain a better understanding of human body during the gross anatomy laboratory.

The changes of cortactin p80/85 isoform profiles and tyrosine phosphorylation status during spermatogenesis in the mouse testis.

Cortactin--an F-actin-binding protein--regulates actin polymerization and plays an important role in cytoskeleton actin dynamics. Cortactin functions are reportedly regulated by changes in its isoform (p80/85) profiles and phosphorylation status. Although essential for spermatogenesis, the exact role of cortactin in the testis has not been well elucidated. Herein, we examined its dynamics in isoform profiles and tyrosine phosphorylation levels during spermatogenesis in mice. Western blot analysis showed that the amount of the p85 isoform of cortactin particularly decreased during stages VI-VIII. In the p80 isoform, cortactin phosphorylations at both tyrosine 421 and 466 were detected during stages XII-V and VI-VIII. For the p85 isoform, tyrosine 466 phosphorylation of cortactin, not 421, was detected during stages XII-V and VI-VIII, and this phosphorylation particularly increased during stages VI-VIII. The tyrosine 466 phosphorylation level of the p85 isoform of cortactin relative to the total amount of the p85 isoform notably increased during stages VI-VIII. Additionally, immunohistochemical analysis showed localization of the tyrosine 466-phosphorylated cortactin around the heads of elongating and elongated spermatids. Finally, we examined the effect of flutamide--an antiandrogen--on cortactin isoform profiles and phosphorylation status. The amount of tyrosine 466-phosphorylated p85 isoform of cortactin relative to the total amount of the p85 isoform of cortactin decreased after flutamide injection, whereas no change was detected with regard to the total amount of cortactin p85 isoform. These data suggest the possibility that localization of the more tyrosine 466-phosphorylated p85 isoform of cortactin around the heads of elongated spermatids is important for stages VII-VIII processes and that its phosphorylation site of the p85 isoform might be a target for creating a novel contraceptive and treating infertility in the future.

[Trial to stimulate learning motivation of medical students in the dissection practice "teaching assistant system"].

At the Medical School of Chiba University, educational dissection tours have been conducted for intra- and extramural students in other programs, such as students of nursing. In the 2006 school year there were more than 1,500 students. As presented in a previous report, we tested an educational program in which our medical students teach other students parts of splanchnology, neurology, and myology to promote student understanding of human physiology through their own teaching. Since this system, termed the "teaching assistant system," was fairly laborious for many medical students, we attempted to improve it by decreasing the students' load and reducing the frequency of teaching from several times to once during the one-term dissection practice. We assessed the improved method with questionnaires for medical students who had studied at the school in 2006 and 2007 (n = 206) before and after teaching other students. The response rate for the questionnaires was 91.3% (n = 188). The results were as follows. (1) Most medical students (69.7%) realized that the task of teaching had stimulating effects on their own learning motivation. (2) According to most of their evaluations (80.4%), the duties of teaching involved in the previous assistant system were laborious. In contrast, the ratio of medical students who considered teaching to be laborious decreased by about half (55.3%) in the present improved system. (3) Most students (79.8%) were satisfied with the teaching assistant system. We concluded that the improved teaching assistant system was effective for the dissection practice.

Exposure of juvenile female mice to isoflavone causes lowered expression of estrogen-related receptor gamma gene in vagina.

In our previous study, the vaginal opening (VO) day of C57BL/6 mice was accelerated several days by chronic exposure to a 0.05% isoflavone (IF) fortified diet. The purpose of this study was to investigate whether the acceleration of VO by IF (1) has a critical window, (2) is modified by IF exposure combined with 17beta-estradiol (E2), and (3) has any relation with gene expressions of estrogen-related receptors (ERRs). As a result, we determined that the critical window for the acceleration of VO was between 15 and 21 days postnatal. The combined effect of E2 and IF was thought to be additional in the acceleration of VO. The gene expression of ERRgamma was significantly decreased in vagina by IF. The reduction of ERRgamma may have two possible sequelae: disarrangement of vaginal development and high risk of vaginal cancer. In conclusion, IF exposure has a critical window for acceleration of VO and may have adverse effect on mouse vagina.

The contamination levels of organochlorines and the pattern of gene expressions in human umbilical cords from intra-pairs of twins at delivery.

In this study, we examined the contamination levels of organochlorines and the patterns of gene expressions using umbilical cords of twins. The contamination levels of total PCBs, HCB and HCHs of intra-pair of twins were close to each other, but that of DDTs were not so as the others. It shows that the placental or fetal factor may influence the transfer or the accumulation of DDTs. The patterns of gene expressions of intra-pair of twins were similar to each other. It may because the environmental factor (sharing same mother), genetic factor or the both of twins are similar. This study gave us some information to understand the fetal exposure to organochlorines. Moreover, it showed the possibility that the pattern of gene expression in umbilical cord reflected the intra-uterine environment. However, the information from general pattern of the gene expression is limited. Therefore, further investigation is necessary to find new markers not only mRNA but also protein to estimate the effects of fetal exposure of multiple organochlorines.

Early changes in sperm motility, acrosome reaction, and gene expression of reproductive organs in rats treated with sulfasalazine.

Previously, we reported that decreased epididymal expression of CD59 and decay accelerating factor (DAF) genes may affect sperm motility and the acrosome reaction in rats treated long-term (28 days) with sulfasalazine. To investigate the early effects of sulfasalazine on the male reproductive tract, we presently examined sperm motility, the acrosome reaction, and gene expression in the testes and epididymides of rats treated with sulfasalazine for 1, 7 or 14 days. Reduced sperm motility and acrosome reactions were noted on day 7, however, there were no remarkable changes in testicular gene expression. On the other hand, attenuated epididymal gene expression of CD59 and DAF was observed as early as day 1. As CD59 and DAF are secreted from the epididymis and play a role in sperm maturation, we hypothesize that sulfasalazine affects sperm maturation as an early effect and that CD59 and DAF genes are related to the negative effect.

Effect of exposure to high isoflavone-containing diets on prenatal and postnatal offspring mice.

Isoflavone (IF), a type of phytoestrogen, has multiple beneficial effects, but too much phytoestrogen can have adverse effects on offspring. To examine whether chronic exposure to high IF has adverse effects on reproductive development, mice offspring were exposed to IF through dietary administration to dams during pregnancy and lactation and to the offspring directly after weaning until sacrifice. In male offspring, there was no difference between the IF group and controls; however, in female offspring in the IF group, remarkably earlier puberty and induction of multioocyte follicles on postnatal day (PND) 21 were observed. Gene expression levels of estrogen receptor beta decreased in the ovary and vagina on PND 21. These results suggest that chronic exposure to higher than normal levels of IF induces alterations in the reproductive development of female mice through an estrogenic effect.

Neonatal administration of diethylstilbestrol has adverse effects on somatic cells rather than germ cells.

Neonatal administration of diethylstilbestrol (DES) to rodents has adverse effects on spermatogenesis. However, not many studies have been conducted to determine which type of cell - germ or somatic - is the major target of DES. In order to clarify this, we tried reciprocal germ cell transplantation--transplantation of germ cells from DES-treated mice into intact mice and germ cells from normal mice into DES-treated mice. The donor germ cells were tagged with the green fluorescent protein (GFP) gene in order to distinguish the exogenous germ cells from the endogenous cells. Moreover, to obtain a large number of spermatogonia from the testes of adult mice, we performed fractionation by centrifugation with Percoll. Consequently, we found that the germ cells collected from DES-treated mice have differentiated into normal sperms in normal seminiferous tubules. However, in the case of the transplantation of normal germ cells into the seminiferous tubules of DES-treated mice, defective spermatogenesis was observed. In conclusion, DES has adverse effects on the somatic cells that are involved in spermatogenesis rather than the germ cells.

Identification and characterization of novel and unknown mouse epididymis-specific genes by complementary DNA microarray technology.

To examine epididymal function, we attempted to identify highly expressed genes in mouse epididymis using a cDNA microarray containing PCR products amplified from a mouse epididymal cDNA library. We isolated one novel and four known genes-lymphocyte cytosolic protein 1 (Lcp1), complement subcomponents C1r/C1s, Uegf protein, and bone morphogenetic protein and zona pellucida-like domains 1 (Cuzd1), transmembrane epididymal protein 1 (Teddm1), and whey acidic protein 4-disulfide core domain 16 (Wfdc16)-with unknown functions in the epididymis. The novel gene, designated Serpina1f (serine peptidase inhibitor [SERPIN], clade A, member 1f), harbors an open reading frame of 1 233 bp encoding a putative protein of 411 amino acids, including a SERPIN domain. These five genes were predominantly expressed in the epididymis as compared to other organs. In situ hybridization analysis revealed their epididymal region-specific expression patterns. Real-time RT-PCR analysis revealed a significant increase in mRNA expression of these genes around puberty. Castration decreased their expression, except forLcp1. Testosterone (T) restored these reduced expressions, except forTeddm1; however, this restoration was not observed with 17 beta-estradiol (E2). Administration of T and E2 combination recovered the Serpina1f mRNA concentration; this recovery was also observed with T alone. However, the recovery of Cuzd1and Wfdc16mRNA concentrations was inadequate. Neonatal diethylstilbestrol treatment suppressed the Cuzd1, Wfdc16, and Serpina1f mRNA expression in the epididymis of 8-week-old mice; this was not observed with E2. These results suggest that our microarray system can provide a novel insight into the epididymal function on a molecular basis, and the five genes might play important roles in the epididymis.