Prednisone vs Placebo and Live Birth in Patients With Recurrent Implantation Failure Undergoing In Vitro Fertilization: A Randomized Clinical Trial.

Importance: Implantation failure remains a critical barrier to in vitro fertilization. Prednisone, as an immune-regulatory agent, is widely used to improve the probability of implantation and pregnancy, although the evidence for efficacy is inadequate. Objective: To determine the efficacy of 10 mg of prednisone compared with placebo on live birth among women with recurrent implantation failure. Design, Setting, and Participants: A double-blind, placebo-controlled, randomized clinical trial conducted at 8 fertility centers in China. Eligible women who had a history of 2 or more unsuccessful embryo transfer cycles, were younger than 38 years when oocytes were retrieved, and were planning to undergo frozen-thawed embryo transfer with the availability of good-quality embryos were enrolled from November 2018 to August 2020 (final follow-up August 2021). Interventions: Participants were randomized (1:1) to receive oral pills containing either 10 mg of prednisone (n = 357) or matching placebo (n = 358) once daily, from the day at which they started endometrial preparation for frozen-thawed embryo transfer through early pregnancy. Main Outcomes and Measures: The primary outcome was live birth, defined as the delivery of any number of neonates born at 28 or more weeks' gestation with signs of life. Results: Among 715 women randomized (mean age, 32 years), 714 (99.9%) had data available on live birth outcomes and were included in the primary analysis. Live birth occurred among 37.8% of women (135 of 357) in the prednisone group vs 38.8% of women (139 of 358) in the placebo group (absolute difference, -1.0% [95% CI, -8.1% to 6.1%]; relative ratio [RR], 0.97 [95% CI, 0.81 to 1.17]; P = .78). The rates of biochemical pregnancy loss were 17.3% in the prednisone group and 9.9% in the placebo group (absolute difference, 7.5% [95% CI, 0.6% to 14.3%]; RR, 1.75 [95% CI, 1.03 to 2.99]; P = .04). Of those in the prednisone group, preterm delivery occurred among 11.8% and of those in the placebo group, 5.5% of pregnancies (absolute difference, 6.3% [95% CI, 0.2% to 12.4%]; RR, 2.14 [95% CI, 1.00 to 4.58]; P = .04). There were no statistically significant between-group differences in the rates of biochemical pregnancy, clinical pregnancy, implantation, neonatal complications, congenital anomalies, other adverse events, or mean birthweights. Conclusions and Relevance: Among patients with recurrent implantation failure, treatment with prednisone did not improve live birth rate compared with placebo. Data suggested that the use of prednisone may increase the risk of preterm delivery and biochemical pregnancy loss. Our results challenge the value of prednisone use in clinical practice for the treatment of recurrent implantation failure. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR1800018783.

Sensitive Silicon Nanowire Ultraviolet B Photodetector Induced by Leakage Mode Resonances.

Ultraviolet photodetectors (UVPDs) have played an important role both in civil and military applications. While various studies have shown that traditional UVPDs based on wide-band-gap semiconductors (WBSs) have excellent device performances, it is, however, undeniable that the practical application of WBS-based UVPDs is largely limited by the relatively high fabrication cost. In this work, we propose a new silicon nanowire (Si NW) UVPD that is very sensitive to UVB light illumination. The Si NWs with a diameter of about 36 nm are fabricated by a metal-assisted chemical etching method. Performance analysis revealed that the Si NW device was only sensitive to UVB light and almost blind to illumination in the visible and near-infrared regions. Such abnormal spectral selectivity was associated with the leakage mode resonances (LMRs) of the small diameter, according to our theoretical simulation. Under 300 nm illumination, the responsivity, external quantum efficiency, and specific detectivity were estimated to be 10.2 AW-1, 4.22 × 103%, and 2.14 × 1010 Jones, respectively, which were comparable to or even higher than those of some WBS-based UVPDs. These results illustrate that the small dimension Si NWs are potential building blocks for low-cost and high-performance UVPDs in the future.

Androgen Excess Increases Food Intake in a Rat Polycystic Ovary Syndrome Model by Downregulating Hypothalamus Insulin and Leptin Signaling Pathways Preceding Weight Gain.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common reproductive and metabolic disorder characterized by high androgen levels. The aim of this study was to evaluate the effects of hyperandrogenism on the hypothalamus and subsequently on the food intake and obesity in females. METHODS: A dihydroxy testosterone (DHT)-induced rat model was established to recapitulate the hyperandrogenism features of PCOS patients. Body weight and food intake of the rats were recorded. The food intake of DHT-induced rats was restricted by pair feeding to exclude possible effects of weight gain on the hypothalamus. The expression levels of relevant proteins and mRNAs in the hypothalamus and primary hypothalamic neurons exposed to DHT were analyzed by Western blotting and RT-PCR, respectively. The leptin levels in the serum and cerebrospinal fluid (CSF) were measured, and leptin was injected via the intracerebroventricular (ICV) route to test the leptin sensitivity of the hypothalamus. RESULTS: The excessive prepuberty androgen levels in the DHT-induced rats markedly elevated food intake prior to weight gain. Consistent with this, the expression of neuropeptide Y and agouti-related peptide mRNAs was upregulated, which occurred prior to obesity and even with restricted food intake. In addition, the hypothalamic sensitivity to insulin and leptin was also impaired in the DHT-induced rats before obesity and with restricted food intake. DHT significantly reduced the leptin levels in the CSF, and ICV injection of leptin inhibited the DHT-induced increase in food intake. CONCLUSIONS: Androgen excess increased food intake in rats and promoted obesity by downregulating insulin and leptin signaling in the hypothalamus, most likely by suppressing leptin levels in the CSF.

Involvement of kisspeptin in androgen-induced hypothalamic endoplasmic reticulum stress and its rescuing effect in PCOS rats.

Endoplasmic reticulum (ER) stress, with adaptive unfolded protein response (UPR), is a key link between obesity, insulin resistance and type 2 diabetes, all of which are often present in the most common endocrine-metabolic disorder in women of reproductive age, polycystic ovary syndrome (PCOS), which is characterized with hyperandrogenism. However, the link between excess androgen and endoplasmic reticulum (ER) stress/insulin resistance in patients with polycystic ovary syndrome (PCOS) is unknown. An unexpected role of kisspeptin was reported in the regulation of UPR pathways and its involvement in the androgen-induced ER stress in hypothalamic neuronal cells. To evaluate the relationship of kisspeptin and ER stress, we detected kisspeptin and other factors in blood plasm of PCOS patients, rat models and hypothalamic neuronal cells. We detected higher testosterone and lower kisspeptin levels in the plasma of PCOS than that in non-PCOS women. We established a PCOS rat model by dihydrotestosterone (DHT) chronic exposure, and observed significantly downregulated kisspeptin expression and activated UPR pathways in PCOS rat hypothalamus compared to that in controls. Inhibition or knockdown of kisspeptin completely mimicked the enhancing effect of DHT on UPR pathways in a hypothalamic neuronal cell line, GT1-7. Kp10, the most potent peptide of kisspeptin, effectively reversed or suppressed the activated UPR pathways induced by DHT or thapsigargin, an ER stress activator, in GT1-7 cells, as well as in the hypothalamus in PCOS rats. Similarly, kisspeptin attenuated thapsigargin-induced Ca2+ response and the DHT- induced insulin resistance in GT1-7 cells. Collectively, the present study has revealed an unexpected protective role of kisspeptin against ER stress and insulin resistance in the hypothalamus and has provided a new treatment strategy targeting hypothalamic ER stress and insulin resistance with kisspeptin as a potential therapeutic agent.

[Community Characteristics of Methanogens and Methanogenic Pathways in Salt-tolerant Rice Soil].

It is known that methanogens play a critical role in the carbon cycle in soil, while methanogen community characteristics and their environmental influencing factors in the soil planted with salt-tolerant rice remain unclear. In this study, methanogen abundance, community composition, and relationships with environmental factors in soils planted with the salt-tolerant rice (YC1703) and ordinary rice (Lindao 10) were evaluated in the rice improvement demonstration base of Qingdao Wisdom Agricultural Industry using real-time fluorescence quantitative PCR and Illumina high-throughput sequencing. The results indicated that the abundance and community richness of methanogens in Lindao 10 soil were significantly higher than those in YC1703 soil, and methanogens in YC1703 soil exhibited higher diversity. The combined effects of rice varieties, rice growth period, and environmental factors had impacts on the methanogen community. The hydrogenotrophic methanogens were dominant in the YC1703 and Lindao 10 soils; thus, we speculated that the dominant pathway of methane production in these soils was hydrogenotrophic methanogenesis.

Single-cell analysis of nonhuman primate preimplantation development in comparison to humans and mice.

BACKGROUND: Genetic programs underlying preimplantation development and early lineage segregation are highly conserved across mammals. It has been suggested that nonhuman primates would be better model organisms for human embryogenesis, but a limited number of studies have investigated the monkey preimplantation development. In this study, we collect single cells from cynomolgus monkey preimplantation embryos for transcriptome profiling and compare with single-cell RNA-seq data derived from human and mouse embryos. RESULTS: By weighted gene-coexpression network analysis, we found that cynomolgus gene networks have greater conservation with human embryos including a greater number of conserved hub genes than that of mouse embryos. Consistently, we found that early ICM/TE lineage-segregating genes in monkeys exhibit greater similarity with human when compared to mouse, so are the genes in signaling pathways such as LRP1 and TCF7 involving in WNT pathway. Last, we tested the role of one conserved pre-EGA hub gene, SIN3A, using a morpholino knockdown of maternal RNA transcripts in monkey embryos followed by single-cell RNA-seq. We found that SIN3A knockdown disrupts the gene-silencing program during the embryonic genome activation transition and results in developmental delay of cynomolgus embryos. CONCLUSION: Taken together, our study provided new insight into evolutionarily conserved and divergent transcriptome dynamics during mammalian preimplantation development.

Morphological and anatomical characteristics of exserted stigma sterility and the location and function of SlLst (Solanum lycopersicum Long styles) gene in tomato.

KEY MESSAGE: Anatomical changes in and hormone roles of the exserted stigma were investigated, and localization and functional analysis of SlLst for the exserted stigma were performed using SLAF-BSA-seq, parental resequencing and overexpression of SlLst in tomato. Tomato accession T431 produces stigmas under relatively high temperatures (> 27 °C, the average temperature in Harbin, China, in June-August), so pollen can rarely reach the stigma properly. This allows the percentage of male sterility exceed 95%, making the use of this accession practical for hybrid seed production. To investigate the mechanism underlying the exserted stigma male sterility, the morphological changes of, anatomical changes of, and comparative endogenous hormone (IAA, ABA, GA3, ZT, SA) changes in flowers during flower development of tomato accessions DL5 and T431 were measured. The location and function of genes controlling exserted stigma sterility were analyzed using super SLAF-BSA-seq, parental resequencing, comparative genomics and the overexpression of SlLst in tomato. The results showed that an increase in cell number mainly caused stigma exsertion. IAA played a major role, while ABA had an opposite effect on stigma exertion. Moreover, 26 candidate genes related to the exserted stigma were found, located on chromosome 12. The Solyc12g027610.1 (SlLst) gene was identified as the key candidate gene by functional analysis. A subcellular localization assay revealed that SlLst is targeted to the nucleus and cell membrane. Phenotypic analysis of SlLst-overexpressing tomato showed that SlLst plays a crucial role during stigma exsertion.

[Peroxiredoxin 4 protects the testis from heat stress].

OBJECTIVE: To explore the protective effect of Peroxiredoxin 4 (PRDX4) on the testes undergoing heat stress in PRDX4 knockout mice. METHODS: Twenty-four C57BL/6 mice underwent CRISPR/Cas9-mediated total knockout of the PRDX4 gene and another 24 wild-type mice were used as controls. At 9 weeks of age, the rats were subjected to 15-minute testicular heat stress in 43℃ water once a day for 3 days, or in 25℃ water as the control. Before and at 1 day and 5 weeks after treatment, 4 from each group were sacrificed respectively and their testes harvested for observation of histological changes by HE staining, detection of the apoptosis of spermatogenic cells by TUNEL and determination of the expression of PRDX4 by Western blot and those of the oxidative stress factors hydroxynonenal (HNE) and 8-OHdG by immunohistochemistry. RESULTS: No statistically significant differences were observed in testicular histology, the apoptosis rate of spermatogenic cells, and the expressions of HNE and 8-OHdG between the PRDX4 knockout mice and wild-type controls (P > 0.05). After 1-day 43℃ heat stress, the PRDX4 knockout mice showed a significantly increased apoptosis rate of spermatogenic cells as compared with the baseline (ï¼»38.65 ± 2.57ï¼½% vs ï¼»0.46 ± 0.06ï¼½%, P < 0.01), and so did the wild-type controls (ï¼»13.21 ± 1.43ï¼½% vs ï¼»0.33 ± 0.01ï¼½%, P < 0.01), higher in the PRDX4 knockout than in the wild-type control group even at 5 weeks after heat stress (ï¼»3.09 ± 0.16ï¼½% vs ï¼»1.45 ± 0.11ï¼½%, P < 0.01). The PRDX4 knockout mice also exhibited a markedly upregulated expression of 8-OHdG (38.25 ± 1.19 vs 19.54 ± 1.13, P < 0.01), and so did the wild-type controls (24.30 ± 1.65 vs 18.22 ± 1.18, P < 0.01), higher in the PRDX4 knockout than in the wild-type control group even at 5 weeks after heat stress (25.40 ± 1.57 vs 23.25 ± 1.48, P < 0.01). The expression of HNE, however, showed no statistically significant difference before and at 1 day after 43℃ heat stress either in the PRDX4 knockout mice or in the wild-type controls (P > 0.05), though remarkably higher in the former than in the latter group at 5 weeks after treatment (28.57 ± 0.56 vs 19.00 ± 1.35, P < 0.01). The expression of 8-OHdG was also higher in the PRDX4 knockout than in the wild-type control group at 5 weeks, but with no statistically significant difference (P > 0.05). CONCLUSIONS: PRDX4 can effectively protect the testis from heat stress and promote the restoration of its spermatogenic function.

[High-level androgen enhances the differentiation of hESCs into male primordial germ cells].

OBJECTIVE: To observe the effects of different concentrations of testosterone on the differentiation of human embryonic stem cells (hESCs) into early male germ cells and investigate the potential impact of high-level androgen exposure in early pregnancy in women with polycystic ovary syndrome (PCOS) on the fertility and primordial germ cell reserve of the male offspring in adulthood. METHODS: We used 2 µmol/L retinoic acid to induce the differentiation of hESCs (46, XY) into male germ cells in vitro and meanwhile treated them with testosterone (T) at 0 mol/L, 3×10－7 mol/L, 5×10－7 mol/L, 15×10－7 mol/L, 45×10－7 mol/L, and 135×10－7 mol/L, respectively. We collected the cell samples at 0, 4, 7 and 14 days to determine the expressions of the specific genes and compare the differentiation process and efficiency of the male germ cells in different stages. RESULTS: There was no difference in the morphology of the hESCs treated with different concentrations of testosterone in the same differentiation stage. The expression of the marker gene DAZL in the primordial germ cells peaked on the 4th day of differentiation, significantly higher in the 15×10－7, 45×10－7 and 135×10－7 mol/L groups than in the 3×10－7 mol/L group (P < 0.05), and that of the specific gene SCP3 in the early-meiosis germ cells began to increase on the same day, more significantly in the 45×10－7mol/L than in the 3×10－7 mol/L and 5×10－7 mol/L groups (P < 0.01), and peaked on the 7th day, dramatically higher in the 15×10－7, 45×10－7 and 135×10－7 mol/L groups than in the 3×10－7 mol/L group (P < 0.01). Immunofluorescence staining and flow cytometry showed a T concentration-dependent increase in the expression of DAZL at 4 days and those of SCP3 and VASA at 7 days. Moreover, the expression of the androgen receptor (AR) in the hESCs began to rise on the 4th day and kept going up till the 14th day, higher in the high-concentration than in the low-concentration T groups in the same stage of differentiation, though with no statistically significant difference (P > 0.05). CONCLUSIONS: Exposure to high-level androgen during the differentiation of hESCs into early male germ cells can induce earlier expression of AR and earlier differentiation of hESCs into early male germ cells, which may result in insufficient reserve of male primary germ cells in the male offspring of PCOS women and affect their fertility after adulthood. hESCs can be used as an in vitro model to study the effects of intrauterine hyperandrogen on the reproductive development of male offspring in PCOS patients, which is also contributive to researches on the etiology of male infertility.

Peroxiredoxin 4, a new oxidative stress marker in follicular fluid, may predict in vitro fertilization and embryo transfer outcomes.

BACKGROUND: Peroxiredoxin 4 (Prdx4), a member of the Prdx family, can catalyze the reduction of reactive oxygen species. This study aims to explore whether Prdx4 can serve as an effective marker in follicular fluid (FF) for predicting in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycle outcomes. METHODS: In this prospective study, all participants were recruited from the center of clinical reproductive medicine from 2017 September to 2018 December. Women with tubal or male factor infertility undergoing their first IVF/ICSI cycle were recruited (n=138). FF samples from each patient were collected on the day of oocyte retrieval. Prdx4 concentrations were measured, and the correlation between Prdx4 levels and IVF outcomes was analyzed. RESULTS: The results showed that pregnant women had higher levels of Prdx4 than nonpregnant women. Prdx4 was positively correlated with the oocyte fertilization rate (r =0.334; P=0.011) and good quality embryo rate (r =0.326; P=0.013). Furthermore, we found that the clinical pregnancy rate was positively correlated with Prdx4 levels in a concentration-dependent manner in the Prdx4 quartiles (<13.38, 13.83-16.93, 16.93-22.93, >22.93 ng/mL). The fertilization rates, clinical pregnancy rates and live pregnancy rates were all significantly higher in the highest Prdx4 quartile group than in the lowest quartile. Moreover, the results indicated that Prdx4 had an area under the receiver operating characteristic curve (AUC) of 0.754, corresponding to an optimal cutoff point of 22.30 ng/mL. CONCLUSIONS: Our results provide evidence that higher expression of antioxidants, such as Prdx4, in the FF of IVF patients tends to indicate a higher likelihood of pregnancy through an oocyte quality mechanism.

Aminopeptidase N expression in the endometrium could affect endometrial receptivity.

Aminopeptidase N (ANPEP) is a membrane-bound zinc-dependent peptidase. Although it is widely believed that ANPEP acts as an important angiogenesis regulatory factor, there are few studies about its function in the female reproductive system. In our previous research, we applied Isobaric Tags for Relative and Absolute Quantitation (iTRAQ) to analyze the influence of different controlled superovulation treatments for Assisted Reproductive Technology, In Vitro Fertilization and Embryo Transfer (IVF-ET)) patients from a global proteomic perspective to search for potential biomarkers associated with endometrium receptivity and embryo implantation. ANPEP is one of the proteins that demonstrated differential expression between different treatment groups and may be closely associated with endometrial receptivity. In this study, we assessed the expression of ANPEP in the endometrium of mice at different ages and found it to be highest in the mature period. We also detected ANPEP expression in the endometrium of IVF-ET patients in the proliferative, preimplantation and implantation stages, and the highest expression level of ANPEP was found in the last group. Human primary endometrial stromal cells were infected with an adenovirus expression vector containing the ANPEP gene and a green fluorescent protein (GFP) fusion protein; the mRNA levels of HOXA-10, LIF, and integrin ß3 were found to be increased. Therefore, we conclude that ANPEP could be involved in the regulation of endometrial receptivity.

Frozen versus fresh single blastocyst transfer in ovulatory women: a multicentre, randomised controlled trial.

BACKGROUND: Elective single embryo transfer (eSET) has been increasingly advocated, but concerns about the lower pregnancy rate after reducing the number of embryos transferred have encouraged transfer of multiple embryos. Extended embryo culture combined with electively freezing all embryos and undertaking a deferred frozen embryo transfer might increase pregnancy rate after eSET. We aimed to establish whether elective frozen single blastocyst transfer improved singleton livebirth rate compared with fresh single blastocyst transfer. METHODS: This multicentre, non-blinded, randomised controlled trial was undertaken in 21 academic fertility centres in China. 1650 women with regular menstrual cycles undergoing their first cycle of in-vitro fertilisation were enrolled from Aug 1, 2016, to June 3, 2017. Eligible women were randomly assigned to either fresh or frozen single blastocyst transfer. The randomisation sequence was computer generated, with block sizes of two, four, or six, stratified by study site. For those assigned to frozen blastocyst transfer, all blastocysts were cryopreserved and a delayed frozen-thawed single blastocyst transfer was done. The primary outcome was singleton livebirth rate. Analysis was by intention to treat. This trial is registered at the Chinese Clinical Trial Registry, number ChiCTR-IOR-14005405. FINDINGS: 825 women were assigned to each group and included in analyses. Frozen single blastocyst transfer resulted in higher rates of singleton livebirth than did fresh single blastocyst transfer (416 [50%] vs 329 [40%]; relative risk [RR] 1·26, 95% CI 1·14-1·41, p<0·0001). The risks of moderate or severe ovarian hyperstimulation syndrome (four of 825 [0·5%] in frozen single blastocyst transfer vs nine of 825 [1·1%] in fresh single blastocyst transfer; p=0·16), pregnancy loss (134 of 583 [23·0%] vs 124 of 481 [25·8%]; p=0·29), other obstetric complications, and neonatal morbidity were similar between the two groups. Frozen single blastocyst transfer was associated with a higher risk of pre-eclampsia (16 of 512 [3·1%] vs four of 401 [1·0%]; RR 3·13, 95% CI 1·06-9·30, p=0·029). INTERPRETATION: Frozen single blastocyst transfer resulted in a higher singleton livebirth rate than did fresh single blastocyst transfer in ovulatory women with good prognosis. The increased risk of pre-eclampsia after frozen blastocyst transfer warrants further studies. FUNDING: The National Key Research and Development Program of China.

Hypoxia-induced and HIF1α-VEGF-mediated tight junction dysfunction in choriocarcinoma cells: Implications for preeclampsia.

INTRODUCTION: Accumulated data indicate that placental hypoxia is implicated in the pathogenesis of preeclampsia (PE). Tight junction (TJ) is important structure that sustains normal placental barrier function, its dysregulation under hypoxia has been observed. This study was designed to explore hypoxia-induced TJ dysfunction in trophoblast cells and its possible involvement in PE pathophysiology. METHODS: Choriocarcinoma cells were grown in a monolayer and treated with cobalt chloride (CoCl2) to induce hypoxia. TJ architecture was assessed using transmission electron microscopy, and locations of TJ proteins were determined by immunofluorescence. TJ functions were assessed by transepithelial electrical resistance (TER) and increased cell paracellular permeability (CPP), and the expression of TJ-related proteins, HIF-1α and VEGF was measured. RESULTS: The TJ functions of trophoblast cells were significantly altered by hypoxia; TER decreased and CPP increased in a time- and concentration-dependent manner. Significant alterations in TJ protein expression and increases in HIF1α and VEGF expression were observed in hypoxic cells, and these effects were attenuated by pretreatment with YC-1. Moreover, corresponding changes in TJ protein expression were also detected in preeclamptic placentas. CONCLUSION: These data demonstrate that trophoblast cells undergo significant changes in TJ protein expression under hypoxic conditions and highlight the potential significance of the HIF1α-VEGF axis in the regulation of TJ structure and function in the preeclamptic placenta.

Can peri-ovulatory putrescine supplementation improve egg quality in older infertile women?

The aging-related decline in fertility is an increasingly pressing medical and economic issue in modern society where women are delaying family building. Increasingly sophisticated, costly, and often increasingly invasive, assisted reproductive clinical protocols and laboratory technologies (ART) have helped many older women achieve their reproductive goals. Current ART procedures have not been able to address the fundamental problem of oocyte aging, the increased rate of egg aneuploidy, and the decline of developmental potential of the eggs. Oocyte maturation, which is triggered by luteinizing hormone (LH) in vivo or by injection of human chorionic gonadotropin (hCG) in an in vitro fertilization (IVF) clinic, is the critical stage at which the majority of egg aneuploidies arise and when much of an egg's developmental potential is established. Our proposed strategy focuses on improving egg quality in older women by restoring a robust oocyte maturation process. We have identified putrescine deficiency as one of the causes of poor egg quality in an aged mouse model. Putrescine is a biogenic polyamine naturally produced in peri-ovulatory ovaries. Peri-ovulatory putrescine supplementation has reduced egg aneuploidy, improved embryo quality, and reduced miscarriage rates in aged mice. In this paper, we review the literature on putrescine, its occurrence and physiology in living organisms, and its unique role in oocyte maturation. Preliminary human data demonstrates that there is a maternal aging-related deficiency in ovarian ornithine decarboxylase (ODC), the enzyme responsible for putrescine production. We argue that peri-ovulatory putrescine supplementation holds great promise as a natural and effective therapy for infertility in women of advanced maternal age, applicable in natural conception and in combination with current ART therapies.

Serum levels of trace elements in children born after assisted reproductive technology.

INTRODUCTION: The health and development of newborn children born via assisted reproductive technology (ART), as well as their health in adulthood, have raised great concern. This study was designed to investigate whether ART children have differences in the levels of trace elements compared with naturally conceived children. METHODS: This study included those ART children and controls aged 1 to 12 years assessed with a follow-up protocol. Serum levels of the trace elements zinc, copper, iron, calcium, magnesium and lead were determined and analyzed. RESULTS: There were no significant differences in age, gender or body weight between the ART and control groups. There were no significant differences in the rates of deficiency or excess of trace elements between the two groups. Serum lead levels in children born via ART were significantly higher than those in the controls, whereas the levels of zinc and iron were significantly decreased in the ART group, although these levels were still within the normal ranges. DISCUSSION: These results indicate the need to monitor the blood levels of zinc, iron and lead in ART children aged 1-6 years old. These findings contribute to our understanding on the long-term safety of ART and may facilitate screening for potential diseases related to trace elements.

Recent Progress in Magnetron Sputtering Technology Used on Fabrics.

The applications of magnetron sputtering technology on the surface coating of fabrics have attracted more and more attention from researchers. Over the past 15 years, researches on magnetron sputtering coated fabrics have been mainly focused on electromagnetic shielding, bacterial resistance, hydrophilic and hydrophobic properties and structural color etc. In this review, recent progress of the technology is discussed in detail, and the common target materials, technologies and functions and characterization of coated fabrics are summarized and analyzed. Finally, the existing problems and future prospects of this developing field are briefly proposed and discussed.

[Preimplantation genetic diagnosis for infertile males with autosomal dominant polycystic kidney disease].

OBJECTIVE: Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common genetic renal diseases, which may cause oligoasthenospermia and azoospermia and result in male infertility. This study aimed to analyze the outcomes of preimplantation genetic diagnosis (PGD) in male patients with ADPKD-induced infertility. METHODS: We retrospectively analyzed the clinical data on 7 male patients with ADPKD-induced infertility undergoing PGD from April 2015 to February 2017, including 6 cases of oligoasthenospermia and 1 case of obstructive azoospermia, all with the PKD1 gene heterozygous mutations. Following intracytoplasmic sperm injection (ICSI), we performed blastomere biopsy after 5 or 6 days of embryo culture and subjected the blastomeres to Sureplex whole-genome amplification, followed by haplotype linkage analysis, Sanger sequencing, array-based comparative genomic hybridization to assess the chromosomal ploidy of the unaffected embryos, and identification of the unaffected euploid embryos for transfer. RESULTS: One PGD cycle was completed for each of the 7 patients. Totally, 26 blastocysts were developed, of which 12 were unaffected and diploid. Clinical pregnancies were achieved in 6 cases following 7 cycles of frozen embryo transplantation, which included 5 live births and 1 spontaneous abortion. CONCLUSIONS: For males with ADPKD-induced infertility, PGD may contribute to high rates of clinical pregnancy and live birth and prevent ADPKD in the offspring as well. This finding is also meaningful for the ADPKD patients with normal fertility.

[Differentiation of embryonic stem cells from the embryos of the couples with male asthenozoospermia and Robertsonian translocation into germ cells].

OBJECTIVE: To assess the risk of male infertility in the offspring conceived through assisted reproductive technology (ART) byin vitroinductionof the differentiation of embryonic stem cells (ESCs) derived from the embryos of the couples with male asthenozoospermia and Robertsonian translocation (RT) into germ cells. METHODS: We established a CCRM16ESC line with the karyotype of 46, XY, +14, rob(13; 14) (q10; q10) from the embryo donated by a patientwithasthenozoospermiaand RT and his wife by isolation of the inner cell mass of blastula, culturing, passaging, and amplification,followed by in vitro induction and differentiationof the ESCs into germ cells with ratinoic acid(RA) at 2 mol/L. Then, we analyzed the process of differentiation and the expressions of its related genes and compared them with those in the normal CCRM23ESCs. RESULTS: CCRM16 showed the typical characteristics of ESCs, expressing the pluripotency makers of NANOG, OCT4, TRA-1-181 and SSEA4, forming embryoid bodies, and differentiating into three germlayer tissues in vitro and in vivo. Intervention with 2 mol/LRAinduced direct differentiation of the ESCs into germ cells. The expressions of the primordial germ cell marker geneDAZLand the meiosis marker geneSCP3were markedly decreased in the CCRM16 as compared with those in the normal CCRM23 ESCs. CONCLUSIONS: The CCRM16ESC linewith the karyotype of46, XY, +14, rob(13; 14) (q10; q10) has thetypical characteristics of ESCs but an abnormal process of differentiation into germ cells in the early stage. In vitroinductionof the differentiation of ESCs into germ cells can be used for assessing the risk of male infertility in the offspring conceived through ART for asthenozoospermia patients.

Immunosuppressive effect of arsenic trioxide on islet xenotransplantation prolongs xenograft survival in mice.

The role of arsenic trioxide (As2O3) in inhibiting immune rejection and prolonging islet allograft survival has been identified in islet allotransplantation. This study aims to explore the role of As2O3 in islet xenotransplantation and the action mechanism. The streptozotocin (STZ) was used in C57BL/6 mice to induce the type 1 diabetes mellitus (T1DM) for xenotransplantation models establishment. Donor islets were isolated by digesting. The flow cytometry (FCM) was used to analyze lymphocyte types. The blood sugar level was detected by using intraperitoneal glucose tolerance test (IPGTT). The serum level of cytokines was determined by the enzyme-linked immunosorbent assay (ELIZA). The cell proliferation was measured by MTT assay. The mRNA levels were quantified with qRT-PCR. As2O3 prolonged the survival of the recipient mice but had no influence on body weight. As2O3 protected the function of xenograft in insulin secretion and suppressed immune rejection of recipient. As2O3 inhibited proliferation of T lymphocyte and increased the proportion of Foxp3+ regulatory T cells in recipient mice. As2O3 inhibited activation and promoted clonal anergy of T lymphocyte. As2O3 decreased total number of B cells and reduced partial antibody levels in recipient mice. As2O3 and leflunomide showed a synergistic effect in suppressing islet xenotransplant rejection. As2O3 prolongs islet xenograft survival by inhibiting cellular immune response, and increasing Foxp3+ regulatory T cells, while decreasing partial antibody levels in serum.

Abnormal CFTR Affects Glucagon Production by Islet α Cells in Cystic Fibrosis and Polycystic Ovarian Syndrome.

Glucagon, produced by islet α cells, functions to increase blood glucose. Abnormal glucose levels are often seen in cystic fibrosis (CF), a systematic disease caused by mutations of the CF transmembrane conductance regulator (CFTR), and in polycystic ovarian syndrome (PCOS), an endocrine disorder featured with hyperandrogenism affecting 5-10% women of reproductive age. Here, we explored the role of CFTR in glucagon production in α cells and its possible contribution to glucagon disturbance in CF and PCOS. We found elevated fasting glucagon levels in CFTR mutant (DF508) mice compared to the wildtypes. Glucagon and prohormone convertase 2 (PC2) were also upregulated in CFTR inhibitor-treated or DF508 islets, as compared to the controls or wildtypes, respectively. Dihydrotestosterone (DHT)-induced PCOS rats exhibited significantly lower fasting glucagon levels with higher CFTR expression in α cells compared to that of controls. Treatment of mouse islets or αTC1-9 cells with DHT enhanced CFTR expression and reduced the levels of glucagon and PC2. The inhibitory effect of DHT on glucagon production was blocked by CFTR inhibitors in mouse islets, and mimicked by overexpressing CFTR in αTC1-9 cells with reduced phosphorylation of the cAMP/Ca2+ response element binding protein (p-CREB), a key transcription factor for glucagon and PC2. These results revealed a previously undefined role of CFTR in suppressing glucagon production in α-cells, defects in which may contribute to glucose metabolic disorder seen in CF and PCOS.