Unidirectional titanium fiber-reinforced porous titanium with mechanical properties suitable for load-bearing biomaterials.

Biomaterials for load-bearing implants are expected to exhibit mechanical biocompatibility of low stiffness and high strength for avoiding stress shielding and failure of the implants in vivo, respectively. This study aimed to develop porous titanium (Ti) reinforced with long Ti fibers so that the porous Ti exhibited low Young's modulus and high tensile strength. The unidirectional Ti fiber-reinforced porous Ti with porosities (p) of 40%-58% and volume percentages of Ti fiber (Vf) of 3%-33% has been successfully fabricated via the space holder technique. Mechanical testing revealed that its strength was improved, compared with uniform porous Ti because Ti fibers prevent microscopic damage progress. The porous Ti with p = 40% and Vf = 33% exhibited the strength of 233 MPa and Young's modulus of 26 GPa, which were higher than and comparable to those of natural bones, respectively. Hence, the Ti fiber-reinforced porous Ti exhibited ideal mechanical properties for implant applications.

Medical issues for female athletes returning to competition after childbirth.

BACKGROUND: In recent years, the number of athletes who aim to return to competition after childbirth has increased. However, few international reports have investigated complications during pregnancy, and changes in physical function after childbirth in many athletes. OBJECTIVE: To conduct a retrospective investigation of medical problems during pregnancy, and postpartum, in female athletes who aim to return to competition after childbirth, and to identify the barriers and facilitators for their return. METHODS: A voluntary web-based survey was aimed at former female athletes who became pregnant with their first child and gave birth during their active sports career. The survey items included respondent background, their exercise activities during and after childbirth, perinatal complications, mode of delivery, symptoms and physical function after childbirth. The participants were divided into a vaginal delivery group and a cesarean section group. RESULTS: Three hundred and twenty-eight (29.1 ± 5.1 years old) former athletes were included in the analysis, and about half reported undertaking exercise during pregnancy. The most common perinatal complication was anemia (27.4%). The appearance of any symptoms after childbirth, including low back pain (44.2%) and urinary incontinence (39.9%), was reported by 80.5%. The rate of urinary incontinence may be higher in the vaginal delivery than in the cesarean section group (p = 0.05). The most common physical decline after childbirth was in muscular strength, followed by speed and endurance. CONCLUSION: Addressing pregnancy-associated anemia and managing low back pain is critical for athletes aiming to return to competition after childbirth. Additionally, interventions to reduce the risk for and treat urinary incontinence are important. In addition, in order to return to competition after childbirth, it is important to strengthen muscles, especially the lower limbs and trunk, as well as to create a training program that takes into account the sport/events.

Age and menstrual cycle may be important in establishing pregnancy in female athletes after retirement from competition.

BACKGROUND: Although it has been shown that amenorrhea associated with low energy availability or relative energy deficiency in sport affects body physiology in female athletes, the association between menstrual dysfunction during active sports careers and reproductive function after retirement is not clear. OBJECTIVE: To investigate the association between menstrual dysfunction during their active sports career and post-retirement infertility in female athletes. METHODS: A voluntary web-based survey was aimed at former female athletes who had become pregnant and gave birth to their first child after retirement. Nine multiple-choice questions were included, on maternal age, competition levels and menstrual cycles during active sports careers, time from retirement to pregnancy, the time of resumption of spontaneous menstruation after retirement, conception method, and mode of delivery, etc. Regarding cases of primary and secondary amenorrhea among the abnormal menstrual cycle group, only those whose spontaneous menstruation had not recovered from retirement to the time of pregnancy were included in the study. The association between the presence of abnormal menstrual cycles from active sports careers to post-retirement pregnancy and the implementation of infertility treatment was evaluated. RESULTS: The study population included 613 female athletes who became pregnant and gave birth to their first child after retiring from competitive sports. Of the 613 former athletes, the infertility treatment rate was 11.9%. The rate of infertility treatment was significantly higher in athletes with abnormal than normal menstrual cycles (17.1% vs. 10.2%, p = 0.0225). Multivariable logistic regression analysis showed that maternal age (adjusted odds ratio [OR] 1.194; 95% confidence interval [CI] 1.129, 1.262) and abnormal menstrual cycles (OR and 1.903; adjusted OR 1.105, 3.278) were the relevant factors for infertility treatment. CONCLUSION: It was suggested that menstrual dysfunction that persist from active sports careers to post-retirement may be a factor in infertility when trying to conceive after retirement.

Upregulation of autotaxin by oxidative stress via Nrf2 activation: A novel insight into the compensation mechanism in preeclamptic placenta.

The response of autotaxin (ATX)-lysophosphatidic acid (LPA) signaling system to placental oxidative stress (OS) and its significance to preeclampsia were investigated. For this purpose, oxidative stress index (OSI) and ATX levels were measured in the serum of pregnant women with preeclampsia. The expression levels of ATX and LPA receptors were assessed in trophoblast cells under high OS and glucose deprivation/re-oxygenation (OGD/R) conditions, with particular emphasis on the antioxidative nuclear factor erythroid 2-related factor 2 (NRF2) pathway. The influence of ATX-LPA signaling on cell migration was also evaluated using the wound healing assay. ATX concentrations and OSI in the serum were found to be elevated in preeclamptic women. The serum ATX levels were also positively correlated with OSI. Trophoblast cells responded to OS by increasing ATX mRNA expression concomitantly with intranuclear translocation of Nrf2, whereas inhibition of Nrf2 activation reverted this effect. The ATX-LPA signaling pathway facilitated trophoblast cell motility after Nrf2 activation. In conclusion, OS accumulation in preeclamptic placenta may activate the ATX-LPA system in trophoblasts via the Nrf2 pathway to sustain trophoblast functionality.

Anti-ß2-glycoprotein I/HLA-DR Antibody and Adverse Obstetric Outcomes.

Anti-ß2-glycoprotein I/HLA-DR (anti-ß2GPI/HLA-DR) antibody has been reported to be associated with antiphospholipid syndrome and recurrent pregnancy loss (RPL). We conducted a prospective multicenter cross-sectional study aimed at evaluating whether the anti-ß2GPI/HLA-DR antibody is associated with adverse obstetric outcomes and RPL. From 2019 to 2021, serum anti-ß2GPI/HLA-DR antibody levels (normal, <73.3 U) were measured in 462 women with RPL, 124 with fetal growth restriction (FGR), 138 with hypertensive disorders of pregnancy (HDP), 71 with preterm delivery before 34 gestational weeks (preterm delivery (PD) ≤ 34 GWs), and 488 control women who experienced normal delivery, by flow cytometry analysis. The adjusted odds ratios (aORs) of anti-ß2GPI/HLA-DR antibody positivity for adverse obstetric outcomes and RPL were evaluated on the basis of comparisons between the control and each patient group, using multivariable logistic regression analysis. The following were the positivity rates for the anti-ß2GPI/HLA-DR antibody in the patient and control groups: RPL, 16.9%; FGR, 15.3%; HDP, 17.4%; PD ≤ 34 GWs, 11.3%; and the control, 5.5%. It was demonstrated that anti-ß2GPI/HLA-DR antibody positivity was a significant risk factor for RPL (aOR, 3.3 [95% confidence interval {CI} 1.9-5.6], p < 0.001), FGR (2.7 [1.3-5.3], p < 0.01), and HDP (2.7 [1.4-5.3], p < 0.01) although not for PD ≤ 34 GWs. For the first time, our study demonstrated that the anti-ß2GPI/HLA-DR antibody is involved in the pathophysiology underlying FGR and HDP, as well as RPL.

Infrared Spectra in the 1000-100 cm-1 Region Combined with 4000-3000 cm-1 Region to Evaluate the States of Water.

In this study, we evaluated the state of water by performing infrared (IR) spectroscopic analysis in the 4000-100 cm-1 region. The effects of ions on the structure of water molecules were investigated by analyzing specific IR bands of salt solutions in the 1000-100 cm-1 region. Chloride solutions of Li, Na, K, Cs, Ba, and Ca were prepared at different concentrations, and their IR spectra were recorded by the attenuated total reflection method. The isosbestic point was observed in the 1000-100 cm-1 region, and the position was related to the ratio of the Stokes radius and effective ionic radius of each ion. Two bands were identified at around 660 and 400 cm-1 by curve fitting, and the intensity ratio increased linearly with a decrease in water activity. Thus, this demonstrates the potential of the 1000-100 cm-1 region as a marker for the evaluation of water structure subjected to ions. Moreover, it is possible to evaluate different states of water simultaneously by combining this with the band in the 4000-3000 cm-1 region. These results successfully demonstrate the effectiveness of the spectra in the 1000-100 cm-1 region to evaluate the state of water in ionic solutions.

Distribution of the follicular and luteal phase lengths and their age-dependent changes in Japanese women: A large population study.

Purpose: The current definition of menstrual cycle length in a Japanese woman is different from those of WHO definition, and the original data are outdated. We aimed to calculate the distribution of follicular and luteal phases length in modern Japanese women with various menstrual cycles. Methods: This study determined the lengths of the follicular and luteal phases of Japanese women using basal body temperature data collected via a smartphone application from 2015 to 2019, and the data were analyzed using the Sensiplan method. Over 9 million temperature readings from more than 80 000 participants were analyzed. Results: The mean duration of the low-temperature (follicular) phase averaged 17.1 days and was shorter among participants aged 40-49 years. The mean duration of the high-temperature (luteal) phase was 11.8 days. The variance and maximum-minimum difference of the length of the low temperature period were significant in women under 35 years old than women aged more than 35 years. Conclusions: The shortening of the follicular phase in women aged 40-49 years implied a relationship with the rapid decline of ovarian reserve in these women, and the age 35 years old was turning point of ovulatory function.

[Optimal safety management procedures for medications with potent teratogenic properties: a prospective intervention cluster randomized non-inferiority comparative study].

Using the "periodic confirmation sheet" employed in the safety management procedure of thalidomide drugs, we looked at whether patients' knowledge of compliance with the procedure varies depending on the length of the gap between confirmations. In 31 centers, 215 participants were male patients and female patients who might be pregnant participants. Subjects have treated a group of patients who used periodic confirmation slips at the standard confirmation interval and a group of patients who increase the confirmation interval to 4 or 6 months, the % of respondents that correctly answered each of all six questions in questions 1-6 on the second comprehension questionnaire, excluding question 7 to confirm behavior change, was 87.0%. Comparing the percentage of correct answers to all questions the first time and the second time, no pregnancy cases were observed and there was no decline in the percentage of accurate responses after the second attempt for either group. One cannot judge changes in behavior. The mixed-effect model also additionally demonstrated non-inferiority in the patient group with the extended confirmation interval (a difference of -6.7% in the proportion of correct answers on the comprehension test (95%CI: -20.3-7.0%)), thus it appears that going forward, both male patients and female patients of potential pregnancy should complete the periodic confirmation form once every 4 or 6 months.

A DNA barcode reference library for the native woody seed plants of Japan.

DNA barcode databases are increasingly available for a range of organisms, facilitating the wide application of DNA barcode-based studies. Here we announce the development of a comprehensive DNA barcode reference library of Japanese native woody seed plants representing 43 orders, 99 families, 303 genera and 834 species, and comprising 77.3% of the genera and 72.2% of the species of native woody seed plants in Japan. A total of 6216 plant specimens were collected from 223 sites across the subtropical, temperate, boreal and alpine biomes in Japan with most species represented by multiple accessions. This reference library utilized three chloroplast DNA regions (rbcL, trnH-psbA and matK) and consists of 14,403 barcode sequences. Individual regions varied in their identification rates, with species-level and genus-level rates for rbcL, trnH-psbA and matK based on blast being 57.4%/96.2%, 78.5%/99.1% and 67.8%/98.1%, respectively. Identification rates were higher using region combinations, with total species-level rates for two region combinations (rbcL & trnH-psbA, rbcL & matK and trnH-psbA & matK) ranging between 90.6% and 95.8%, and for all three regions being equal to 98.6%. Genus-level identification rates were even higher, ranging between 99.7% and 100% for two region combinations and being 100% for the three regions. These results indicate that this DNA barcode reference library is an effective resource for investigations of native woody seed plants in Japan using DNA barcodes and provides a useful template for the development of libraries for other components of the Japanese flora.

Improving water dispersibility and bioavailability of luteolin using microemulsion system.

We have studied the physiological effects and health functions of luteolin, especially focusing on its absorption and metabolism. Recent studies have reported the advantages of microemulsion to improve the bioavailability of poorly water-soluble compounds, including luteolin. In the present study, we aimed to evaluate the absorption and metabolic profile of luteolin delivered in microemulsion system via oral intake. First, we prepared water-dispersed luteolin (WD-L) using a microemulsion-based delivery system and confirmed that WD-L has superior water dispersibility compared to free luteolin (CO-L) based on their particle size distributions. Following administration of WD-L and CO-L to rats, we detected high level of luteolin-3'-O-ß-glucuronide and lower levels of luteolin, luteolin-4'-O-ß-glucuronide, and luteolin-7-O-ß-glucuronide in plasma from both CO-L and WD-L groups, indicating that the metabolic profile of luteolin was similar for both groups. On top of that, we found a 2.2-fold increase in the plasma area under the curve (AUC) of luteolin-3'-O-ß-glucuronide (main luteolin metabolite) in WD-L group (vs. CO-L). Altogether, our results suggested that delivering luteolin by microemulsion system improve its oral bioavailability without affecting its metabolite profile. This evidence thereby provides a solid basis for future application of microemulsion system for optimal delivery of luteolin.

Progressive Changes in Lumbopelvic Alignment during the Three Month-Postpartum Recovery Period.

Pregnancy-related lumbopelvic pain is a common musculoskeletal problem, and postural changes are believed to be involved in these disorders. However, the lumbopelvic alignment changes in postpartum women remain unclear. This study aimed to determine whether there are changes in lumbopelvic alignment following vaginal or cesarean delivery and when these alignment changes occur after delivery. Thirty postpartum females (PP group) and 20 nulliparous female controls (CTL group) underwent anteroposterior, lateral pelvic, and lower-back X-ray in a static upright position. Digital radiographic images were analyzed and three radiographic variables, the pelvic incidence, pubic symphysis width, and sacral slope, were measured. The pubic symphysis width of the PP group was significantly larger immediately and one month after childbirth (PP group: 6.0 ± 1.1 mm (immediately), 5.0 ± 1.2 mm (one month); CTL group: 3.4 ± 0.4 mm; F = 31.79, p < 0.001). The sacrum slope in the PP group was significantly larger than in the CTL group 1 month after childbirth (PP group: 39.9 ± 6.6°; CTL group: 32.8 ± 5.1°; F = 2.59, p = 0.05). A two-way analysis of variance indicated no statistically significant main effects or interaction effects between the delivery modes on the pubic symphysis width or the sacrum slope. This study suggested that the course of lumbopelvic alignment progressed towards recovery for at least one month, and that these changes were independent of the delivery method.

Prenatal diagnosis of pyriform sinus fistula using ultrasonography by detecting the communication to the pharynx.

OBJECTIVE: Pyriform sinus fistula (PSF) is a congenital anomaly which originates from the pharyngeal pouch. PSF is initially recognized as a cyst around the fetal neck, but accurate prenatal diagnosis of the disease is challenging. We aimed to report the key findings and tips in accurately distinguishing PSF from other differential diagnosis by which enables detection of the communication of the nuchal cyst and the pharynx. CASE REPORT: We report a case in which we were able to diagnose PSF as early as 18 weeks of gestation with ultrasonography. We used epiglottis as a landmark, and detected an unilobular cyst arising from the pharynx. CONCLUSION: Ultrasonography is a powerful tool in prenatal diagnosis of PSF especially at early stage of pregnancy. By detecting the epiglottis, it can locate the communication of the nuchal cyst and the pharynx, and thereby enables an accurate diagnosis of PSF.

High-Resolution X-ray Phase-Contrast Imaging and Sensory and Rheometer Tests in Cooked Edamame.

Although several reports exist on the use of X-ray analysis in vegetables and fruits to examine internal disorders, cavities, and porosity, information on X-ray analysis of qualities, such as texture, is lacking as well as information on X-ray analysis of legumes. Therefore, this study aimed to perform X-ray analysis with sensory and rheometer tests in cooked vegetable soybean (edamame). Edamame is popular worldwide due to its deliciousness and nutritional value. Vascular structures and cracks around them were clearly visualized using X-ray phase-contrast computed tomography (CT) imaging. In addition, we observed the fine structure of the seed coat, which could be important for seed development, germination, and processing. The density in the edamame beans declined as the boiling time increased, promoting a reduction in hardness described in sensory and rheometer tests. The reduction in density proceeded from the gap between cotyledons, the opposite side of the hypocotyl, and the crack. Collectively, the findings show that the high-resolution X-ray phase-contrast CT imaging conducted in a nondestructive manner may help in effectively evaluating the quality of vegetables and in observing the internal structures related to plant development.

Anatomical identification of ischial spines applicable to intrapartum transperineal ultrasound based on magnetic resonance imaging of pregnant women.

OBJECTIVE: Intrapartum transperineal ultrasound is considered useful in judging fetal head descent; however, the inability to detect ischial spines on ultrasound images has been a drawback to its legitimacy. The current study aimed to determine the anatomical location of ischial spines, which can be directly applied to intrapartum transperineal ultrasound images. METHOD: Based on magnetic resonance imaging (MRI) of 67 pregnant women at 33+2 [31+6-34+0] weeks gestation (median [interquartile range: IQR]), we calculated the angle between the pubic symphysis and the midpoint of ischial spines (midline symphysis-ischial spine angle; mSIA), which is theoretically equivalent to the angle of progression at fetal head station 0 on ITU, by determining spatial coordinates of pelvic landmarks and utilizing spatial vector analysis. Furthermore, we measured symphysis-ischial spine distance (SID), defined as the distance between the vertical plane passing the lower edge of the pubic symphysis and the plane that passes the ischial spines. RESULTS: As a result, mSIA was 109.6° [105.1-114.0] and SID 26.4 mm [19.8-30.7] (median, [IQR]). There was no correlation between mSIA or SID and maternal characteristics, including physique. CONCLUSIONS: We established a novel method to measure the components of the pelvic anatomy by analyzing the three-dimensional coordinates of MRI data and identified the anatomical location of ischial spines which can be applied to ultrasound images. Our results provide valuable evidence to enhance the reliability of intrapartum transperineal ultrasound in assessing fetal head descent by considering the location of ischial spines.

The impact of fetal growth restriction in diagnosing preeclampsia on the severity of maternal features.

AIM: We aimed to assess the impact of fetal growth restriction (FGR) as a diagnostic criterion for preeclampsia (PE) on the severity of maternal preeclamptic features by comparing it with other diagnostic criteria for PE, maternal organ dysfunction. METHODS: We performed a retrospective cohort study of singleton pregnancies. Based on the status at diagnosis, PE cases preceded by FGR without maternal organ dysfunction (Group F; n = 28) and those preceded by maternal organ dysfunction without FGR (Group M; n = 87) were analyzed. RESULTS: Group F had an earlier PE diagnosis (32.5 ± 4.9 vs. 36.7 ± 3.5 weeks, p < 0.01) and delivery (33.7 ± 4.5 vs. 37.5 ± 3.1 weeks, p < 0.01) than Group M. No significant differences in maternal morbidities were observed between the groups, including severe hypertension (75.0 vs. 60.0%), need for intravenous antihypertensives (42.9 vs. 48.3%) or magnesium sulfate (60.7 vs. 54.5%), or a composite of major maternal complications (17.9 vs. 21.8%). When limited to early-onset PE diagnosed before 34 weeks of gestation (17 and 17 cases in Group F and M, respectively), the frequencies of maternal morbidities (severe hypertension: 70.6 vs. 52.9%, intravenous antihypertensives: 35.3 vs. 35.3%, magnesium sulfate: 58.8 vs. 47.1%, major complications: 29.4 vs. 23.5%) and the duration from diagnosis until delivery (11.2 ± 14.7 vs. 16.5 ± 21.7 days) were comparable between two groups. CONCLUSIONS: Our results suggest that the presence of FGR on PE diagnosis is associated with the development of severe maternal symptoms as much as that of maternal organ dysfunction at diagnosis, and it may be reasonable to include FGR in PE diagnostic criteria.

Influence of Strain Gradient on Fatigue Life of Carbon Steel for Pressure Vessels in Low-Cycle and High-Cycle Fatigue Regimes.

This paper discusses how the strain gradient influences the fatigue life of carbon steel in the low-cycle and high-cycle fatigue regimes. To obtain fatigue data under different strain distributions, cyclic alternating bending tests using specimens with different thicknesses and cyclic tension-compression tests were conducted on carbon steel for pressure vessels (SPV235). The crack initiation life and total failure life were evaluated via the strain-based approach. The experimental results showed that the crack initiation life became short with decreasing strain gradient from 102 to 106 cycles in fatigue life. On the other hand, the influence of the strain gradient on the total failure life was different from that on the crack initiation life: although the total failure life of the specimen subjected to cyclic tension-compression was also the shortest, the strain gradient did not affect the total failure life of the specimen subjected to cyclic bending from 102 to 106 cycles in fatigue life. This was because the crack propagation life became longer in a thicker specimen. Hence, these experimental results implied that the fatigue crack initiation life could be characterized by not only strain but also the strain gradient in the low-cycle and high-cycle fatigue regimes.

Proposed Management Policy for Pregnant Women with Loeys-Dietz Syndrome Following Prophylactic Aortic Root Replacement Based on Experience from a Tertiary Care Center.

Loeys-Dietz syndrome (LDS) is a connective tissue disorder with a high incidence of aortic dissection (AD). After treating two previously reported cases of postpartum AD in women with LDS following prophylactic aortic root replacement (ARR), we succeeded in managing a 30-year-old primigravida with no AD during her peripartum period. On the basis of the patient's stated desire to conceive during preconception counseling, a multidisciplinary team was assembled. She conceived naturally after receiving prophylactic ARR and beta-blocker treatment. Multidisciplinary patient care included precise blood pressure management, continuation of beta-blocker treatment, cardiovascular assessment with echocardiogram, regional anesthesia during labor, prevention of lactation, and resumption of angiotensin II receptor blocker therapy immediately after delivery. On the basis of our assessment of three cases, including this case, and a literature review, we propose a peripartum management strategy for patients with LDS following prophylactic ARR.

The metabolic stress-activated checkpoint LKB1-MARK3 axis acts as a tumor suppressor in high-grade serous ovarian carcinoma.

High-grade serous ovarian carcinoma (HGSOC) is the most aggressive gynecological malignancy, resulting in approximately 70% of ovarian cancer deaths. However, it is still unclear how genetic dysregulations and biological processes generate the malignant subtype of HGSOC. Here we show that expression levels of microtubule affinity-regulating kinase 3 (MARK3) are downregulated in HGSOC, and that its downregulation significantly correlates with poor prognosis in HGSOC patients. MARK3 overexpression suppresses cell proliferation and angiogenesis of ovarian cancer cells. The LKB1-MARK3 axis is activated by metabolic stress, which leads to the phosphorylation of CDC25B and CDC25C, followed by induction of G2/M phase arrest. RNA-seq and ATAC-seq analyses indicate that MARK3 attenuates cell cycle progression and angiogenesis partly through downregulation of AP-1 and Hippo signaling target genes. The synthetic lethal therapy using metabolic stress inducers may be a promising therapeutic choice to treat the LKB1-MARK3 axis-dysregulated HGSOCs.

Ulipristal acetate simultaneously provokes antiproliferative and proinflammatory responses in endometrial cancer cells.

Ulipristal acetate (UPA), a selective progesterone receptor modulator, is used for the treatment of uterine fibroids and selectively inhibits the proliferation and inflammation of leiomyoma cells. As few studies have focused on the molecular biological mechanism of UPA in Ishikawa endometrial cancer cells, we aimed to identify the effects of UPA on these cells. Ishikawa cells were treated with different concentrations of UPA. Cell viability and colony formation assays were performed to assess the growth of cancer cells, whereas invasion and migration assays were used to measure cell motility and invasiveness. Western blotting, caspase 3/7 assay, TUNEL assay, and flow cytometry were performed to analyze apoptosis. Moreover, expression levels of the proinflammatory cytokines oncostatin M, its receptor, interleukin 6, and interleukin 8 were examined using quantitative real-time PCR. UPA decreased cell viability and growth, thereby inhibiting cell migration and invasion via induction of apoptosis. Contrary to expectation, stand-alone application of UPA increased the expression of the proinflammatory cytokines but concomitant use of UPA and the estrogen receptor antagonist ICI 182,720 decreased it. These data revealed a novel dual role of UPA: It could attenuate cell growth via activation of apoptosis while simultaneously provoking the activation of proinflammatory cytokines in endometrial cancer cells. These indicate that the combination of UPA and an estrogen receptor antagonist may be useful in suppressing the secretion of proinflammatory cytokines by UPA alone.

Suppression of human trophoblast syncytialization by human cytomegalovirus infection.

INTRODUCTION: Placental dysfunction triggers fetal growth restriction in congenital human cytomegalovirus (HCMV) infection. Studies suggest that HCMV infection interferes with the differentiation of human trophoblasts. However, the underlying mechanisms have not been clarified. This study investigated the impact of HCMV infection on gene transcriptomes in cytotrophoblasts (CTBs) associated with placental dysfunction. METHODS: CTBs were isolated from human term placentas, and spontaneous syncytialization was observed in vitro. The transcriptome profiles were compared between CTB groups with and without HCMV infection by cap analysis gene expression sequencing. The effect of HCMV infection on trophoblast differentiation was evaluated by examining cell fusion status using immunocytochemical staining for desmoplakin and assessing the production of cell differentiation markers, including hCG, PlGF, and soluble Flt-1, using ELISA. RESULTS: The expression of the genes categorized in the signaling pathways related to the cell cycle was significantly enhanced in CTBs with HCMV infection compared with uninfected CTBs. HCMV infection hindered the alteration of the gene expression profile associated with syncytialization. This suppressive effect under HCMV infection was concurrent with the reduction in hCG and PlGF secretion. Immunostaining for desmoplakin revealed that HCMV infection reduced the cell fusion of cultured CTBs. These findings imply that HCMV infection has a negative impact on syncytialization, which is indispensable for the maintenance of villous function. DISCUSSION: HCMV infection interferes with gene expression profiles and functional differentiation of trophoblasts. Suppression of syncytialization may be a survival strategy for HCMV to expand infection and could be associated with placental dysfunction.