Diesel exhaust exposure alters the expression of networks implicated in neurodegeneration in zebrafish brains.

Neurodegenerative diseases are a major cause of disability in the world, but their etiologies largely remain elusive. Genetic factors can only account for a minority of risk for most of these disorders, suggesting environmental factors play a significant role in the development of these diseases. Prolonged exposure to air pollution has recently been identified to increase the risk of Alzheimer's and Parkinson's diseases, but the molecular mechanisms by which it acts are not well understood. Zebrafish embryos exposed to diesel exhaust particle extract (DEPe) lead to dysfunctional autophagy and neuronal loss. Here, we exposed zebrafish embryos to DEPe and performed high throughput proteomic and transcriptomic expression analyses from their brains to identify pathogenic pathways induced by air pollution. DEPe treatment altered several biological processes and signaling pathways relevant to neurodegenerative processes, including xenobiotic metabolism, phagosome maturation, and amyloid processing. The biggest induction of gene expression in brains was in Cyp1A (over 30-fold). The relevance of this expression change was confirmed by blocking induction using CRISPR/Cas9, which resulted in a dramatic increase in sensitivity to DEPe toxicity, confirming that Cyp1A induction was a compensatory protective mechanism. These studies identified disrupted molecular pathways that may contribute to the pathogenesis of neurodegenerative disorders. Ultimately, determining the molecular basis of how air pollution increases the risk of neurodegeneration will help in the development of disease-modifying therapies.

Air Pollution and the Risk of Parkinson's Disease: A Review.

Parkinson's disease, as well as other neurodegenerative disorders, are primarily characterized by pathological accumulation of proteins, inflammation, and neuron loss. Although there are some known genetic risk factors, most cases cannot be explained by genetics alone. Therefore, it is important to determine the environmental factors that confer risk and the mechanisms by which they act. Recent epidemiological studies have found that exposure to air pollution is associated with an increased risk for development of Parkinson's disease, although not all results are uniform. The variability between these studies is likely due to differences in what components of air pollution are measured, timing and methods used to determine exposures, and correction for other variables. There are several potential mechanisms by which air pollution could act to increase the risk for development of Parkinson's disease, including direct neuronal toxicity, induction of systemic inflammation leading to central nervous system inflammation, and alterations in gut physiology and the microbiome. Taken together, air pollution is an emerging risk factor in the development of Parkinson's disease. A number of potential mechanisms have been implicated by which it promotes neuropathology providing biological plausibility, and these mechanisms are likely relevant to the development of other neurodegenerative disorders such as Alzheimer's disease. This field is in its early stages, but a better understanding of how environmental exposures influence the pathogenesis of neurodegeneration is essential for reducing the incidence of disease and finding disease-modifying therapies. © 2022 International Parkinson and Movement Disorder Society.

NDRG1 is expressed in human granulosa cells: An implicative role of NDRG1 in the ovary.

Purpose: N-myc downstream-regulated gene 1 (NDRG1) is expressed in various human tissues and plays a role in regulating cellular proliferation, angiogenesis, and hypoxia sensing. However, the role of NDRG1 in the ovary remains poorly understood. Therefore, we investigated NDRG1 expression and the role of NDRG1 in the human ovary. Methods: Follicular fluid (FF) and luteinized granulosa cells were collected from follicles during oocyte retrieval. KGN cells were cultured with cobalt chloride (CoCl2, a hypoxia-mimicking agent) and/or echinomycin. mRNA, protein levels and secretion, and localization were assessed by real-time PCR, Western blotting, ELISA, and immunohistochemical analysis, respectively. KGN cells were also transfected with NDRG1 siRNA for 72 h. Results: NDRG1 protein was expressed in luteinized granulosa cells. NDRG1 concentration was positively correlated with vascular endothelial growth factor (VEGF) and progesterone concentrations in FF. CoCl2-induced hypoxic stress significantly increased NDRG1 and VEGF mRNA and protein and hypoxia-inducible factor-1α expression compared with those in the controls. The CoCl2-induced overexpression of NDRG1 and VEGF was suppressed by echinomycin. Transfection with NDRG1 siRNA significantly suppressed the release of progesterone in the culture medium. Conclusions: These results indicate that ovarian NDRG1 may play important roles in follicular development, especially in the early luteinization of pre-ovulatory follicles.

The transcription factor HAND2 up-regulates transcription of the IL15 gene in human endometrial stromal cells.

Cyclic changes of the human endometrium, such as proliferation, secretion, and decidualization, occur during regular menstrual cycles. Heart- and neural crest derivatives-expressed transcript 2 (HAND2) is a key transcription factor in progestin-induced decidualization of human endometrial stromal cells (ESCs). It has been suggested that HAND2 regulates interleukin 15 (IL15), a key immune factor required for the activation and survival of uterine natural killer (uNK) cells. Activated uNK cells can promote spiral artery remodeling and secrete cytokines to induce immunotolerance. To date, no studies have evaluated the transcription factors that regulate IL15 expression in human ESCs. In the present study, we examined whether HAND2 controls IL15 transcriptional regulation in human ESCs. Quantitative RT-PCR and histological analyses revealed that HAND2 and IL15 levels increase considerably in the secretory phase of human endometrium tissues. Results from ChIP-quantitative PCR suggested that HAND2 binds to a putative HAND2 motif, which we identified in the upstream region of the human IL15 gene through in silico analysis. Using a luciferase reporter assay, we found that the upstream region of the human IL15 gene up-regulates reporter gene activities in response to estradiol and a progestin representative (medroxyprogesterone) in ESCs. The upstream region of the human IL15 gene also exhibited increasing responsiveness to transfection with a HAND2 expression vector. Of note, deletion and substitution variants of the putative HAND2 motif in the upstream region of IL15 did not respond to HAND2 transfection. These findings confirm that HAND2 directly up-regulates human IL15 transcription in ESCs.

Matrix Metalloproteinases in Human Decidualized Endometrial Stromal Cells.

Cyclic changes, such as growth, decidualization, shedding, and regeneration, in the human endometrium are regulated by the reciprocal action of female hormones, such as estradiol (E2), and progesterone (P4). Matrix metalloproteases (MMPs) and tissue inhibitors of MMPs (TIMPs) control the invasion of extravillous trophoblast cells after implantation. Several MMPs and TIMPs function in the decidua and endometrial stromal cells (ESCs). Here, we aimed to systematically investigate the changes in MMPs and TIMPs associated with ESC decidualization. We evaluated the expression of 23 MMPs, four TIMPs, and four anti-sense non-coding RNAs from MMP loci. Primary ESC cultures treated with E2 + medroxyprogesterone acetate (MPA), a potent P4 receptor agonist, showed significant down-regulation of MMP3, MMP10, MMP11, MMP12, MMP20, and MMP27 in decidualized ESCs, as assessed by quantitative reverse transcription PCR. Further, MMP15 and MMP19 were significantly upregulated in decidualized ESCs. siRNA-mediated silencing of Heart and Neural Crest Derivatives Expressed 2 (HAND2), a master transcriptional regulator in ESC decidualization, significantly increased MMP15 expression in untreated human ESCs. These results collectively indicate the importance of MMP15 and MMP19 in ESC decidualization and highlight the role of HAND2 in repressing MMP15 transcription, thereby regulating decidualization.

Transcriptional regulation of LGALS9 by HAND2 and FOXO1 in human endometrial stromal cells in women with regular cycles.

Uterine natural killer cells are regulated via surface inhibitory receptors for IL15 and galectin-9 (LGALS9) secreted by endometrial stromal cells (ESCs). However, the mechanism that regulates LGALS9 mRNA levels in ESCs is unclear. The aim of this study is to clarify the transcriptional regulation of LGALS9 in ESCs. Here, LGALS9 mRNA expression levels significantly decreased in the endometrial tissue in the early- to mid-secretory phase, and recovered in the mid- to late-secretory phase, compared to that in the proliferative phase. In ESCs, LGALS9 mRNA expression significantly decreased following estradiol + medroxyprogesterone acetate treatment for 1 day and increased after 12 days compared to that in the control. The transcriptional activity of the LGALS9 upstream region was upregulated by heart and neural crest derivatives expressed 2 (HAND2) and downregulated by forkhead box O1 (FOXO1). In ESCs, HAND2 expression significantly increased throughout the 12 days treatment with steroid hormones, whereas FOXO1 expression significantly increased on Day 1, reached a plateau, and significantly increased again after 6 days of treatment. Levels of FOXO1 phosphorylation (pFOXO1) remained unchanged after a 3-day treatment of ESCs with steroid hormones, but significantly increased following a 12-day treatment. pFOXO1 could not bind to the DNA and was thus unable to directly suppress LGALS9 transcription. Therefore, expression level of HAND2 and phosphorylation status of FOXO1 may determine LGALS9 mRNA expression. This study provides a novel molecular mechanism underlying the transcriptional regulation of LGALS9 mRNA in ESCs, which could be valuable in the treatment of diseases associated with decidualization failure.

Exposure to cigarette smoke affects endometrial maturation including angiogenesis and decidualization.

PURPOSE: To elucidate the effects of cigarette smoking on human endometrial maturation for reproductive function, the authors examined the in vitro effects of cigarette smoke extract (CSE) on angiogenesis and decidualization in primary human endometrial stromal cells (ESCs). METHODS: Endometrial stromal cells were cultured with CSE and/or estradiol-17ß (E2) and medroxyprogesterone acetate (MPA). The mRNA, protein levels, and protein secretion of the angiogenic factors and decidual specific factors were assessed using real-time polymerase chain reaction, Western blot analysis, and enzyme-linked immunosorbent assay, respectively. Decidualization was also monitored by the changes in cellular morphology. RESULTS: Endometrial stromal cell proliferation substantially decreased after dose-dependent treatments with CSE at concentrations above 1%, whereas cell death was induced at treatment concentrations above 1% CSE. Treatments above 0.025% CSE led to increased vascular endothelial growth factor mRNA through hypoxia-inducible factor-1α accumulation. CSE concentrations at 0.01% and 0.025% increased the prolactin expression levels after treatment with E2 and MPA, whereas 0.1% and 0.25% CSE concentrations suppressed prolactin. Similar tendencies were observed in cellular morphology and other decidual specific factors. CONCLUSION: These results suggest that exposure to cigarette smoke affects endometrial appropriate maturation including the processes of angiogenesis and decidualization in the reproductive system.

Concentration of stromal cell-derived factor-1 (SDF-1/CXCL12) in the follicular fluid is associated with blastocyst development.

PURPOSE: To study the association between stromal cell-derived factor-1 (SDF-1/CXCL12) and vascular endothelial growth factor (VEGF) concentrations in individual human ovarian follicles and IVF outcomes. METHODS: Concentrations of SDF-1 and VEGF in 261 follicular fluid samples were measured with enzyme-linked immunosorbent assay. IVF outcome parameters were included in fertilization rate, cleavage rate, embryo morphology on day 3, and blastocyst morphology on day 5. RESULTS: The follicular concentration of SDF-1 and VEGF was not significantly associated with fertilization and cleavage outcome, and embryo morphology. The rates of full blastocysts and good-quality blastocysts were significantly higher in follicles with an SDF-1 concentration of 275-350 pg/mL than in the follicles with SDF-1 concentrations of <200 and ≥350 pg/mL (P < 0.05). The follicular concentration of VEGF was not associated with the blastocyst morphology. CONCLUSION: Our findings showed that follicular concentration of SDF-1, and not VEGF, may be a valuable biochemical marker of blastocyst development.

Motivating Mothers to Recommend Their 20-Year-Old Daughters Receive Cervical Cancer Screening: A Randomized Study.

BACKGROUND: In Japan, the rate of cervical cancer screening is remarkably low, especially among women in their twenties and thirties, when cervical cancer is now increasing dramatically. The aim of this study was to test whether a modified government reminder for 20-year-old women to engage in cervical cancer screening, acting through maternal education and by asking for a maternal recommendation to the daughter to receive the screening, could increase their participation rate. METHODS: In two Japanese cities, 20-year-old girls who had not received their first cervical cancer screening before October of fiscal year 2014 were randomized into two study arms. One group of 1,274 received only a personalized daughter-directed reminder leaflet for cervical cancer screening. In the second group of 1,274, the daughters and their mothers received a combination package containing the same reminder leaflet as did the first group, plus an additional informational leaflet for the mother, which requested that the mother recommend that her daughter undergo cervical cancer screening. The subsequent post-reminder screening rates of these two study arms were compared. RESULTS: The cervical cancer screening rate of 20-year-old women whose mothers received the information leaflet was significantly higher than that for women who received only a leaflet for themselves (11% vs 9%, P = 0.0049). CONCLUSIONS: An intervention with mothers, by sending them a cervical cancer information leaflet with a request that they recommend that their daughter receive cervical cancer screening, significantly improved their daughters' screening rate.

Decidualization of the human endometrium.

BACKGROUND: Decidualization of the human endometrium, which involves a dramatic morphological and functional differentiation of human endometrial stromal cells (ESCs), is essential for the establishment of a successful pregnancy. Decidualization results from a complex interplay of transcription factors, morphogens, cytokines, cell cycle regulators, and signaling pathways. METHODS: Based on a literature review, the regulation of, and the molecular mechanisms involved in, the decidualization of the endometrium are described. MAIN FINDINGS: Progesterone, together with proteins that are regulated by progesterone and/or cyclic adenosine monophosphate, including homeobox A10, forkhead box O1, signal transducers and activators of transcription, and heart and neural crest derivatives expressed transcript 2, forms a critical network for ESC decidualization and is a prerequisite to successful implantation. Decidualized ESCs contribute to the microenvironment at the feto-maternal interface and its direct or indirect influence on extracellular matrix remodeling, regulation of the local immune response, anti-oxidative stress, and angiogenesis (vascular maturation). Impairment of this process is associated with a variety of pregnancy disorders, including infertility, recurrent miscarriages, and uteroplacental disorders. CONCLUSION: A deeper understanding of the process of decidualization is expected to provide new insights into the fields of reproductive biology and reproductive medicine.

Mothers' attitudes in Japan regarding cervical cancer screening correlates with intention to recommend cervical cancer screening for daughters.

BACKGROUND: Cervical cancer and its precancerous lesions caused by human papilloma virus (HPV) are steadily increasing in women in Japan. In comparison with women in other resource-rich countries, young women in Japan have a dismally low screening rate for cervical cancer. Our preliminary research has shown that 20-year-old women in Japan usually ask their mothers for advice regarding their initial cervical cancer screening. The objective of our current research is to determine the social factors among mothers in Japan that are causing them to give advice to their daughters regarding the HPV vaccine and cervical cancer screening. METHODS: The survey's targets were mothers who had 20-year-old daughters. We recruited respondents from the roster of a commercial internet survey panel. We analyzed for correlations between a mother's knowledge concerning cervical cancer, her recent cancer screening history, and the advice she gave to her daughter regarding cervical cancer screening. RESULTS: We obtained 618 valid answers to the survey. Compared with mothers who did not get screening, mothers who had cervical cancer screening had significantly more knowledge about cervical cancer and its screening (p < 0.05). The daughters of mothers with recent screening had received HPV vaccination more often than those of mothers without recent screening (p = 0.018). Mothers with recent screening histories tended more often to encourage their daughters to have cervical cancer screening (p < 0.05). When mothers were properly educated concerning cervical cancer and its screening, they were significantly more likely than before to recommend that their daughters have it (p < 0.0001). CONCLUSIONS: In young Japanese women, given the important role their mothers have in their lives, it is probable that we could improve their cervical cancer screening rate significantly by giving their mothers better medical information, and a chance to experience cervical cancer screening for themselves.

Development of an efficient strategy to improve HPV immunization coverage in Japan.

BACKGROUND: In Japan, new HPV immunizations have dropped dramatically after repeated adverse media reports and a June 2013 temporary suspension of the government's recommendation for the vaccine. The aim of the present study was to develop an efficient strategy to improve HPV immunization coverage across Japan. METHODS: We conducted an internet survey in Japan of mothers of 12-16 year-old girls who were unvaccinated as of May, 2015. The goal was to gather behavioral information from the mothers to develop a strategy for improving Japanese HPV immunization coverage. RESULTS: Valid survey answers were obtained from 2060 mothers. The survey found that a hypothetical restart of a governmental recommendation for the vaccine would induce 4.1 % of all the mothers surveyed to be more likely to encourage vaccination of their daughters, without any other preconditions. This initial result would be followed by a moderate spread of vaccinations to these daughters' close friends and acquaintances, hypothetically resulting in a total vaccination rate of 21.0 % of the targeted age-eligible girls. As a second critical step for improving vaccinations, an educational information sheet integrating the concepts of behavioral economics for changing behaviors was found to be significantly effective for persuading mothers with poorer decision-making facilities, who would otherwise prefer to wait to first see the vaccination of other girls of the same age as their daughter. CONCLUSIONS: Following what we foresee as the inevitable restart of the Japanese government's recommendation for receiving the HPV vaccine, we expect to first see vaccinations occurring in a very small group of girls, the daughters of the most willing mothers, which will be roughly 4 % of those eligible for government paid vaccinations. This will be followed by the spread of vaccinations outward through these girls' circle of friends and acquaintances, and, finally, to the daughters of the most skeptical mothers, those who would await the return of new vaccine safety results from a large group of similarly-aged girls. As a critical step in improving HPV vaccine coverage in Japan, an educational information sheet that integrates the concepts of behavioral economics for changing behaviors can be employed to persuade mothers with poor decision-making facilities.

Project conducted in Hirakata to improve cervical cancer screening rates in 20-year-old Japanese: Influencing parents to recommend that their daughters undergo cervical cancer screening.

AIM: In Japan, the rate of routine cervical cancer screening is quite low, and the incidence of cervical cancer has recently been increasing. Our objective was to investigate ways to effectively influence parental willingness to recommend that their 20-year-old daughters undergo cervical cancer screening. METHODS: We targeted parents whose 20-year-old daughters were living with them. In fiscal year 2013, as usual, the daughter received a reminder postcard several months after they had received a free coupon for cervical cancer screening. In fiscal year 2014, the targeted parents received a cervical cancer information leaflet, as well as a cartoon about cervical cancer to show to their daughters, with a request that they recommend to their daughter that she undergo cervical cancer screening. The subsequent screening rates for fiscal years 2013 and 2014 were compared. RESULTS: The cervical cancer screening rate of 20-year-old women whose parents received the information packet in fiscal year 2014 was significantly higher than for the women who, in fiscal year 2013, received only a simple reminder postcard (P < 0.001). As a result, the total screening rate for 20-year-old women for the whole of the 2014 fiscal year was significantly increased over 2013 (P < 0.001). CONCLUSION: For the first time, we have shown that the parents of 20-year-old daughters can be motivated to recommend that their daughters receive their first cervical cancer screening. This was achieved by sending a cervical cancer information leaflet and a cartoon about cervical cancer for these parents to show to their daughters. This method was significantly effective for improving cervical cancer screening rates.

Effect on HPV vaccination in Japan resulting from news report of adverse events and suspension of governmental recommendation for HPV vaccination.

BACKGROUND: Administration of the human papillomavirus (HPV) vaccine decreased dramatically in Japan after extensive news of adverse vaccine events and suspension of the governmental recommendation for the vaccine. In this study, we investigated the knowledge and acceptance of vaccinated adolescents concerning cervical cancer, cancer screening and the HPV vaccine. Furthermore, we analyzed whether and by how much the news affected acceptance of the vaccination. METHODS: This study was conducted as a part of Osaka Clinical resEArch of HPV vacciNe (OCEAN) study. A questionnaire was distributed to 2,777 study registrants. RESULTS: The response rate was 38%. The recognition rate of the news of the vaccine's adverse events was 80%; it was 68% for awareness of the government's announcement of the suspension of its recommendation for the vaccine. Among those who had a chance to hear or see the negative news during their vaccination period, 46 (60%) continued vaccination while knowing of the news, 22 (29%) discontinued vaccination, and 9 (11%) continued vaccination without an awareness of the news. Reports of the vaccine's adverse events were the main reason for not continuing the vaccination series. Those who consulted doctors after hearing the adverse news were significantly more likely to continue their vaccinations than those who did not. CONCLUSIONS: Our results should help in understanding the need for a strong promotion of vaccine usage and cancer screening after future retraction of the recommendation suspension. This may apply to other countries with an unsatisfactory rate of HPV vaccination due to fears of adverse vaccine events.

Significance of placental CD200 expression in patients with preeclampsia: Comparison between early­ and late­onset patients.

Preeclampsia, characterized by high blood pressure and proteinuria during pregnancy, causes serious complications in both the mother and the fetus. Although there have been several studies on the causes of preeclampsia, the detailed mechanism of this disease remains unclear. Moreover, a few reports have focused on the causes of preeclampsia in number of weeks at onset. The present study aimed to elucidate the differences between early­ and late­onset preeclampsia. This study enrolled patients with preeclampsia from January 2014 to December 2020. They were classified into early­ (<34 weeks) and late­onset (≥34 weeks) preeclampsia groups. The expression profiles of 770 immune­related genes were studied in the placental tissue from five patients each in the early­ and late­onset groups. The expression of CD200 in the trophoblasts of the placenta of 26 and 27 patients in early­ and late­onset groups, respectively, was also analyzed using immunostaining. Analysis of extracted RNA indicated that CD200 was significantly upregulated in the early­onset group compared with late­onset group and normal control. Immunostaining for CD200 demonstrated a significantly increased expression in the early­onset group compared with the late­onset group. The present study demonstrated that upregulation of CD200, which belongs to the immunoglobulin superfamily and is recognized as a molecule that acts in immune tolerance via inhibition of classical macrophage activation, may be associated with early­onset preeclampsia, although it remains unknown whether upregulation of CD200 expression is a cause or effect of the development of early­onset preeclampsia. Early­onset preeclampsia might have a different mechanism from that of late­onset; thus, further studies are needed to clarify the mechanism of these conditions for adequate treatment.

The Regulators of Human Endometrial Stromal Cell Decidualization.

Several factors are important for implantation and subsequent placentation in the endometrium, including immunity, angiogenesis, extracellular matrix, glucose metabolism, reactive oxidative stress, and hormones. The involvement or abnormality of these factors can impair canonical decidualization. Unusual decidualization can lead to perinatal complications, such as disruption of trophoblast invasion. Drastic changes in the morphology and function of human endometrial stromal cells (hESCs) are important for decidualization of the human endometrium; hESCs are used to induce optimal morphological and functional decidualization in vitro because they contain estrogen and progesterone receptors. In this review, we will focus on the studies that have been conducted on hESC decidualization, including the results from our laboratory.

The efficacy of human papillomavirus vaccination in young Japanese girls: the interim results of the OCEAN study.

Human papillomavirus (HPV) vaccine has been used to prevent chronic HPV infection, which accounts for cervical cancer. Japanese Ministry of Health, Labor and Welfare (MHLW) conducted an HPV vaccination campaign in 2010 and the Obstetrical Gynecological Society of Osaka initiated a multicenter, prospective cohort study in Osaka, Japan - OCEAN (Osaka Clinical resEArch of HPV vacciNe) study - to investigate the oncogenic HPV prevalence and the long-term protection rate of HPV vaccine. A total of 2814 participants were enrolled on their visit for HPV vaccination between 12 and 18 years old. Among them, 102 participants received HPV/Pap co-test as primary cancer screening at the age of 20-21. We compared the prevalence in two groups (the vaccinated and the unvaccinated group). HPV infection ratio was significantly lower in the vaccinated group compared to the unvaccinated (12.9% vs. 19.7%; p = .04). In particular, HPV 16 and 18 were not detected in the vaccinated group, while 4.9% of participants in the unvaccinated group were infected (p = .001), suggesting that vaccination provided effective protection against high-risk types of HPV. The cross-protection effect of HPV vaccines was also observed against HPV 31, 45, and 52. Although HPV vaccines were not contributed to the reduction of cervical intraepithelial neoplasia 1 (CIN) (p = .28), CIN2 or worse was not observed in vaccinated group. Our research showed that at the age of 20-21, HPV vaccine inhibited the infection of high-risk HPV and had impacted on the development to CIN2 or worse in Japan.

Immune Tolerance of the Human Decidua.

The endometrium is necessary for implantation, complete development of the placenta, and a successful pregnancy. The endometrium undergoes repeated cycles of proliferation, decidualization (differentiation), and shedding during each menstrual cycle. The endometrium-including stromal, epithelial, vascular endothelial, and immune cells-is both functionally and morphologically altered in response to progesterone, causing changes in the number and types of immune cells. Immune cells make up half of the total number of endometrial cells during implantation and menstruation. Surprisingly, immune tolerant cells in the endometrium (uterine natural killer cells, T cells, and macrophages) have two conflicting functions: to protect the body by eliminating pathogenic microorganisms and other pathogens and to foster immunological change to tolerate the embryo during pregnancy. One of the key molecules involved in this control is the cytokine interleukin-15 (IL-15), which is secreted by endometrial stromal cells. Recently, it has been reported that IL-15 is directly regulated by the transcription factor heart- and neural crest derivatives-expressed protein 2 in endometrial stromal cells. In this review, we outline the significance of the endometrium and immune cell population during menstruation and early pregnancy and describe the factors involved in immune tolerance and their involvement in the establishment and maintenance of pregnancy.

A survey of 20-year-old Japanese women: how is their intention to undergo cervical cancer screening associated with their childhood HPV vaccination status?

INTRODUCTION: In Japan, two groups of women, HPV vaccinated and unvaccinated, are approaching age 20, when they should begin cervical cancer screening. To improve Japan's current poor cervical cancer screening rate, we need to know how these women are thinking about screening. METHODS: We conducted an internet survey of 20-y-old women, exploring their understanding of HPV and cervical cancer screening. We then gave them leaflets with basic information about HPV and cervical cancer, stressing the importance of early detection by screening. We analyzed the leaflet's effects on their attitudes based on their vaccination status. RESULTS: Our study of 618 women found a significantly higher intention for engagement for cervical cancer screening in women HPV-vaccinated as teenagers (29% versus 17%). They were also more aware that: (1) HPV is transmitted by sexual intercourse (49.1% versus 39.2%); (2) the HPV vaccine prevents cervical cancer (49.0% to 34.0%); and (3) the appropriate cervical cancer screening interval is every 2 y (63.3% versus 56.2%). Women in both groups responded well to the leaflet, with significant improvements in intention to receive screening. However, 65%-67% were not swayed. DISCUSSION: HPV-vaccinated women were more knowledgeable about cervical cancer and had a greater intention to receive screening. Our educational leaflet was moderately effective in both groups for increasing intentions to screen, but the majority in both groups were still resistant to screening. CONCLUSION: Japan needs to develop more effective educational programs and tools to vigorously impart the importance of cervical cancer screening.

Studying the Pathophysiology of Parkinson's Disease Using Zebrafish.

Parkinson's disease is a common neurodegenerative disorder leading to severe disability. The clinical features reflect progressive neuronal loss, especially involving the dopaminergic system. The causes of Parkinson's disease are slowly being uncovered and include both genetic and environmental insults. Zebrafish have been a valuable tool in modeling various aspects of human disease. Here, we review studies utilizing zebrafish to investigate both genetic and toxin causes of Parkinson's disease. They have provided important insights into disease mechanisms and will be of great value in the search for disease-modifying therapies.