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BackgroundThrough this prospective study, we aimed to explore the change of molecular modification after the transient scrotal hyperthermia on human sperm.MethodsTen healthy subjects selected with strict screening criteria underwent testicular warming in a 43 °C water bath for 30 min a day for 10 consecutive days. Semen samples were collected 2 weeks before the first heat treatment and 6 weeks after the first heat treatment. Proteins from the samples were labeled with isobaric tags for relative and absolute quantitation and analyzed by two-dimensional liquid chromatography–tandem mass spectrometry.ResultsIn contrast to the control, of the 3446 proteins identified, 61 proteins were deregulated: 28 were up-regulated and 33 were down-regulated. Approximately 95% of the differentially expressed proteins were found to participate in spermatogenesis, fertilization, or other aspects of reproduction. In particular, the expression of sperm motility and energy metabolism-related proteins AKAP4, SPESP1, ODF1, ODF2, GAPDHS, and ACTRT2, validated by western blotting of the proteins obtained from human and mouse samples, tended to be reduced under scrotal hyperthermia.ConclusionsThe results indicated that the proteins AKAP4, ODF1, ODF2, GAPDHS, SPESP1, and ACTRT2, play an important role in the heat-induced reversible reduction in sperm concentration and motility and have the potential to be the biomarkers and clinical targets for scrotal heat treatment induced male infertility.

BACKGROUND Subclinical hypothyroidism (SCH) and thyroid autoimmunity (TAI) are associated with adverse pregnancy outcomes such as pregnancy loss and preterm birth. However, the ability of levothyroxine (LT4) supplementation to attenuate the risks of these outcomes remains controversial. OBJECTIVE AND RATIONALE This systematic review and meta-analysis was conducted to determine the effect of LT4 supplementation on pregnancy loss rate (PLR) and preterm birth rate (PBR) among pregnant women with SCH and TAI. SEARCH METHODS A systematic literature search of the PubMed, EMBASE, Web of Science and Cochrane Controlled Trials Register databases and Clinicaltrials.gov was performed to identify all relevant English studies published up to April 2018. The following terms were used for the search: [subclinical hypothyroidism OR thyroid autoimmunity OR thyroperoxidase antibody (TPO-Ab) OR thyroglobulin antibodies (Tg-Ab)] AND (levothyroxine OR euthyrox) AND [pregnancy outcome OR miscarriage OR abortion OR pregnancy loss OR preterm birth OR premature delivery OR early labo(u)r]. The reference lists of the relevant publications were also manually searched for related studies. Published manuscripts were included if they reported data on pregnancy loss, preterm birth or both. We separately analysed the pooled effects of LT4 supplementation on PLR and PBR in women with SCH and TAI. OUTCOMES Overall, 13 eligible studies including 7970 women were included in the meta-analysis. Eight and five of these studies were randomized controlled trials (RCTs) and retrospective studies, respectively. The pooled results indicated that LT4 supplementation significantly decreased the PLR [relative risk (RR) = 0.56, 95% confidence interval (CI): 0.42-0.75, I2 = 1%, 12 studies] and PBR (RR = 0.68, 95% CI: 0.51-0.91, I2 = 21%, eight studies) in women with SCH and/or TAI. We further found that LT4 supplementation significantly decreased the risk of pregnancy loss (RR = 0.43, 95% CI: 0.26-0.72, P = 0.001, I2 = 0%) but not of preterm birth (RR = 0.67, 95% CI: 0.41-1.12, P = 0.13, I2 = 0%) in women with SCH. Furthermore, LT4 supplementation significantly decreased the risks of both pregnancy loss (RR = 0.63, 95% CI: 0.45-0.89, P = 0.009, I2 = 0%) and preterm birth (RR = 0.68 95% CI: 0.48-0.98, P = 0.04, I2 = 46%) in women with TAI. These results were consistent when only RCTs were included in the analysis. Further, in women with SCH, LT4 supplementation reduced the risk of pregnancy loss in pregnancies achieved by assisted reproduction (RR = 0.27, 95% CI: 0.14-0.52, P < 0.001, I2 = 14%) but not in naturally conceived pregnancies (RR = 0.60, 95% CI: 0.28-1.30, P = 0.13, I2 = 0%). By contrast, in women with TAI, LT4 supplementation reduced the risks of both pregnancy loss (RR = 0.61, 95% CI: 0.39-0.96, P = 0.03, I2 = 0%) and preterm birth (RR = 0.49, 95% CI: 0.30-0.79, P = 0.003, I2 = 0%) in naturally conceived pregnancies but not in pregnancies achieved by assisted reproduction (RR = 0.68, 95% CI: 0.40-1.15, P = 0.15, I2 = 0% for pregnancy loss and RR = 1.20, 95% CI: 0.68-2.13, P = 0.53, I2 not applicable for preterm birth). WIDER IMPLICATIONS This meta-analysis confirmed the beneficial effects of LT4 supplementation, namely the reduced risks of pregnancy loss and preterm birth, among pregnant women with SCH and/or TAI. The different effects of LT4 supplementation on naturally conceived pregnancies and pregnancies achieved by assisted reproduction in women with SCH and/or TAI suggest that these women should be managed separately. Due to the limited number of studies included in this meta-analysis, especially in the subgroup analysis, further large RCTs and fundamental studies are warranted to confirm the conclusions and better clarify the molecular mechanism underlying these associations.

Is humanin present in the human ovary and follicular fluid? What relationship exists between humanin concentration in the follicular fluid and ovarian reserve and clinical outcomes after IVF and intracytoplasmic sperm injection (ICSI)?Follicular fluid samples were collected from 179 patients undergoing their first IVF or ICSI cycle during oocyte retrieval. Ovarian tissues were collected from two patients undergoing surgery for ovarian cysts. Ovarian humanin localization was analysed using immunofluorescence staining. Expression of humanin in granulosa cells was confirmed by reverse transcription polymerase chain reaction (RT-PCR) analysis. Follicular fluid humanin levels were evaluated with enzyme-linked immunosorbent assay. Relationships between follicular fluid humanin levels and ovarian reserve markers and clinical outcomes were analysed.Strong humanin expression was found in the granulosa cells, oocytes and stromal cells of the ovary. Agarose gel electrophoresis of RT-PCR products showed rich humanin mRNA expression in human granulosa cells (119 bp). Follicular fluid humanin concentrations ranged from 86.40 to 417.60 pg/ml. They significantly correlated with FSH (r = -0.21; P0.01), LH (r = -0.18; P = 0.02), antral follicle count (r = 0.27; P0.01), anti-Müllerian hormone (r = 0.24; P = 0.03) and inhibin B (r = 0.46; P0.01) levels. Patients were subdivided into four groups according to follicular fluid humanin concentration quartiles (Q1-Q4). Patients in Q4 were more likely to achieve a pregnancy than Q1 (OR = 3.60; 95% CI 1.09 to 11.84).Humanin concentration in the follicular fluid was positively associated with ovarian reserve and clinical pregnancy rate.

Polycystic ovary syndrome (PCOS), the most common endocrine disorder in women of reproductive age, is characterized by hyperandrogenism and insulin resistance (IR); however, the pathogenesis of local ovarian IR in PCOS remains largely unclear. Humanin, a mitochondria-derived peptide, has been reported to be associated with IR. Our previous study confirmed that humanin is expressed in multiple cell types in the ovary and is present in follicular fluid. However, it remains unknown whether humanin participates in the pathogenesis of local ovarian IR or whether humanin supplementation can improve IR in PCOS patients. In this study, we compared humanin concentrations in follicular fluid from PCOS patients with and without IR. We further investigated the effect of humanin analogue (HNG) supplementation on IR in a rat model of dehydroepiandrosterone-induced PCOS. Humanin concentrations in the follicular fluid were found to be significantly lower in PCOS patients with IR than in those without IR. HNG supplementation attenuated both the increases in the levels of fasting plasma glucose and fasting insulin in rats with PCOS and the decreases in phosphorylation of IRS1, PI3K, AKT, and GLUT4 proteins in the granulosa cells of these rats. Combined supplementation with HNG and insulin significantly improved glucose consumption in normal and humanin-siRNA-transfected COV434 cells. In conclusion, downregulated humanin in the ovaries may be involved in the pathogenesis of IR in PCOS, and exogenous supplementation with HNG improved local ovarian IR through modulation of the IRS1/PI3K/Akt signaling pathway in a rat model. This finding supports the potential future use of HNG as a therapeutic drug for PCOS.

Autophagy and apoptosis are two major modes of cell death. A balanced interplay between both is vital for phagocytic clearance of apoptotic testicular cells. Here, generating a SD rats model-treated with cadmium (Cd) to mimic environmental exposure on human, we show that autophagy and apoptosis present synchronous change trends in Cd-induced testicular injury/self-recovery. Further, the cross-talk of autophagy and apoptosis is investigated in four testicular cell lines (GC-1/GC-2/TM3/TM4 cells) respectively. Results reveal that Cd-exposure for five consecutive weeks induces reproductive toxicity in male rats. After one cycle of spermatogenesis within 8 weeks without Cd, toxic effects are ameliorated significantly. In vitro, we find that PI3K inhibitor 3-MA regulates apoptosis by inhibiting autophagy with mTOR-independent pathway in Cd-treated testicular cells. Conclusively, cross-talk between autophagy and apoptosis regulates testicular injury/recovery induced by Cd via PI3K with mTOR-independent pathway.

BACKGROUND Cold-inducible RNA-binding protein (CIRBP) is associated with cell stress. However, its upstream regulatory factors are still largely unknown. OBJECTIVES This study investigated whether CIRBP expression was regulated by transforming growth factor beta (TGF-β) during the process of heat-induced testicular damage. MATERIALS AND METHODS Ten male adult ICR mice were allocated to heat treatment (scrotal hyperthermia at 43 °C for 30 min, n = 5) and control group (n = 5); CIRBP and TGF-β1, TGF-β2, and TGF-β3 expression levels in the testis in mRNA and protein were analyzed. Then, we conducted in vivo and in vitro studies to investigate the regulatory effects of TGF-β on CIRBP. In the in vivo study, male adult ICR mice were subjected to testicular hyperthermia followed by a local testicular injection of TGF-β antagonist (non-selective TGF-β I/II receptor inhibitor, 5 μg or 10 μg). In the in vitro study, GC2-spd cells were cultured under 43 °C for 30 min or with different TGF-β isoforms (10 ng/mL), and CIRBP expression levels in the testis and GC2-spd cells were analyzed 24 and 48 h, respectively, after treatment. RESULTS As a result, heat treatment significantly downregulated the relative CIRBP mRNA and protein expression (p = 0.006 and 0.011), and significantly upregulated TGF-β2 and TGF-β3 expression levels (p = 0.022 and 0.04, for mRNA, and p = 0.001 for both protein levels). Local testicular injection of 10 μg TGF-β antagonist significantly attenuated heat-induced histological damage to the testes and CIRBP downregulation (p = 0.038). Furthermore, TGF-β2 and TGF-β3 significantly downregulated CIRBP mRNA and protein expression in GC2-spd cells (all p

The aim of our study was to evaluate the effects of ozonised olive oil (OOO) on human sperm in vitro.Human sperm was incubated with OOO for 20 s in vitro. The lowest concentration that completely immobilised all the sperm in 20 s without subsequent recovery of motility was recorded as the minimum effective concentration (MEC). The effects of OOO at MEC on human sperm viability, mitochondrial and acrosomal status, DNA integrity and transmission electron microscopy were observed.Our findings demonstrate that OOO dose-dependently inhibits sperm motility. The MEC of OOO for 100% sperm immobilisation in 20 s was 6 μg/ml. Further experiments showed that sperm ultrastructure, function and DNA integrity were significantly affected after treatment with 6 μg/ml OOO in vitro.OOO has spermicidal potential and may be explored as a promising vaginal contraceptive agent.

// Meng Rao 1, * , Zhengyan Zeng 2, * , Li Tang 1 , Guiping Cheng 3 , Wei Xia 3 and Changhong Zhu 3 1 Department of Reproduction and Genetics, The First Affiliated Hospital of Kunming Medical University, Kunming, China 2 Department of Neurology, The First Affiliated Hospital of Kunming Medical University, Kunming, China 3 Family Planning Research Institute, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China * These authors have contributed equally to this work Correspondence to: Meng Rao, email: rm3816205@163.com Keywords: heat stress; spermatogenesis; microRNA; next-generation sequencing; apoptosis Received: October 07, 2017 Accepted: November 16, 2017 Published: December 04, 2017 ABSTRACT This study aimed to investigate the role of microRNA (miRNA) in heat stress-induced spermatogenic impairment. Testes from 15 adult ICR mice subjected to testicular hyperthermia at 43°C for 30 min and from 15 control mice were collected and pooled into 3 samples. Isolated RNA from these samples was subjected to small RNA high-throughput sequencing, and differentially expressed miRNAs were identified and validated using RT-PCR. The identified miRNAs were further subjected to Gene Ontology and KEGG analyses, which revealed significant enrichment for pathways potentially involved in heat stress-induced spermatogenic impairment. Additionally, a correlation analysis of the relative levels of validated miRNAs with germ cell apoptosis was performed. Of the 11 miRNAs identified as differentially expressed, 8 were validated as consistent with sequencing data. Further analyses suggested that the target genes of those miRNAs were involved in various pathways (e.g., ribosomal, HIF-1, MAPK) that may be critical to heat stress-induced testicular damage. Some identified miRNAs, including miR-449a-3p, miR-92a-1-5p, miR-423-3p, and miR-128-3p, correlated closely with germ cell apoptosis. The study results reveal a detailed miRNA profile of heat stress-induced testicular damage and highlight new and potentially important candidate targets in the process of male infertility.

There has been no previous population-based study reporting the prevalence and risk factors of male lower urinary tract symptoms (LUTS) among men in mainland China. This cross-sectional study was conducted from 2013 to 2014 in three representative provinces of China: Guangdong, Hubei and Jiangsu. 3250 individuals participated in the interviews, which involved a questionnaire covering sociodemographic characteristics, lifestyle, dietary patterns and the International Prostate Symptom Score (IPSS). Blood was collected for lipids, glucose, insulin and reproductive hormone tests. The incidences of LUTS and its obstructive and irritative symptoms were calculated. Risk factors for LUTS were identified using multivariable logistic regression analysis. The prevalence of moderate to severe LUTS and its obstructive and irritative symptoms was 14.3%, 13.1% and 16.1%, respectively, and increased with age. The prevalence in Guangdong was much lower than that in Hubei and Jiangsu in different ages. Increased fasting plasma glucose and decreased HDL-C levels were associated with an increased risk of moderate to severe LUTS (OR = 1.30, 95% CI: 1.02–1.65 and OR = 2.06, 95% CI: 1.08–3.94, respectively). Free testosterone < 0.22 ng/ml decreased the risk of moderate to severe LUTS and obstructive and irritative symptoms by about 20–30%. An inadequate daily intake of vegetables, fruit and water significantly increased the risk of LUTS by 1.3–to 2.0 times. In conclusion, the prevalence of LUTS in Chinese men is high and increases with age. Dietary patterns may be critical for the development of LUTS. Thus, dietary modifications could be a useful strategy for preventing the development of LUTS.

This study aimed to examine the cellular and molecular events that occur in rhesus monkey testes after scrotal hyperthermia. Eight male adult rhesus monkeys were subjected to scrotal hyperthermia at 43°C for 30 min daily for 6 consecutive days. Sperm concentration, reproductive hormones, and testis histology were examined before hyperthermia (day 0), and at 8, 15, 30, 45, 60, 75, and 90 days after the initiation of hyperthermia. iTRAQ-based proteomic analysis was conducted on testicular tissues collected on days 0, 8, and 60 to identify differentially expressed proteins at the early and recovery stages of testicular damage. The sperm concentration was significantly decreased at days 30 and 45 after treatment (p < 0.01) and recovered to baseline at day 60. When compared with day 0, 101 and 24 differentially expressed proteins were identified at days 8 and 60 after heat treatment, respectively. The molecular functions of the differentially expressed proteins at day 8 were mainly nucleic acid binding, unfolded protein binding, nucleotide binding, and nucleoside phosphate binding. Spliceosome was enriched as the most significant pathway at day 8. CIRBP, PSIP1, Sam68, and Decorin were validated and found to be consistent with the proteomic data, indicating the reliability of the proteomic profiles identified in this study. In summary, we suggest that the proteins identified in this study may play important roles in heat-induced spermatogenic impairment. Some of these proteins, such as CIRBP, PSIP1, Sam68, and Decorin, may be early molecular targets responsible for spermatogenesis suppression induced by heat treatment.

The p38αMAPK signaling pathway plays a critical role in female reproduction, but an understanding of its expression in rats remains elusive. This study was carried out to investigate the temporal and spatial expression of p38αMAPK and p-p38αMAPK. Ovarian tissue samples were collected from 2-, 4-, 8-, 12-, 16-, 20- and 30-day-old female rats. Western blotting was used to examine the relative expression of p38αMAPK and p-p38αMAPK in ovarian tissue, and subcellular localization was examined using immunohistochemistry of the rat ovaries at different ages of postpartum. The immunohistochemical results showed that p38αMAPK and p-p38αMAPK were widely expressed in the rat ovaries, mainly localized in the follicle cells and granulosa cells. The expression of p38αMAPK was relatively stable for the different stages of oocytes, whereas the expression of p-p38αMAPK gradually increased. At different stages of granulosa cells, the expression of p38αMAPK was also relatively stable, and the p-p38αMAPK expression showed an upward trend during follicular development. Western blotting revealed that the expression of p38αMAPK in the ovaries was relatively stable, where as p-p38αMAPK expression initially exhibited an increasing trend and subsequently decreased, with a maximum at day 20. The expression patterns of p38αMAPK and p-p38αMAPK in the rat ovaries indicate their possible involvement in folliculogenesis. Taken together, the stage- and cell-specific expression of p-p38αMAPK in rat ovaries indicated that p-p38αMAPK might play a vital role during rat follicular development.

It has been observed that there is an increased incidence of total fertilization failure (TFF) and a low fertilization rate (LFR,25 %) during conventional in vitro fertilization (IVF) treatments involving men with poor sperm motility. These men also exhibit a high sperm DNA fragmentation index (DFI), which has adverse effects on various IVF outcomes. However, the relationship between a high DFI and an increased TFF or LFR during IVF cycles has not been elucidated. Here, we aimed to investigate the association between the sperm DFI and TFF or LFR in IVF cycles involving men with mild-to-moderate asthenozoospermia and normozoospermia.This retrospective study included 116 men diagnosed as mild-to-moderate asthenozoospermia, and 407 men with normozoospermia. The sperm DFI was assessed using the sperm chromatin dispersion (SCD) test.Men in the asthenozoospermia group had a significantly higher incidence of cycles with a TFF or LFR (9.5 % vs 2.7 %, P = 0.01), and these were associated significantly with an increased DFI (P0.01). After adjustment for confounding factors, a TFF or LFR was to correlate significantly with the DFI (odds ratio: 1.188; 95 % confidence interval, 1.035-1.363; P = 0.014). Area under the receiver operating characteristic curve was 0.772. No similar relationships between the DFI and IVF outcomes were observed in the normozoospermia group.For men with mild-to-moderate asthenozoospermia, a high sperm DFI is associated with a decreased fertilization rate and an increased risk of a TFF or LFR. Additional prospectively-designed studies are warranted to confirm our results.

Background: Overt thyroid diseases have been identified as risk factors for female infertility. However, it remains largely unclear whether subclinical hypothyroidism (SCH), a very common thyroid d...

A limited number of studies have explored whether the role of circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) in the pathogenesis of acute myocardial infarction (AMI) is sex specific. The purpose of the present study was to examine sex differences in plasma PCSK9 in Chinese patients with AMI. In this study, a total of 281 records from patients presenting with AMI were analyzed.We compared hospital data and plasma PCSK9 levels by sex difference for inpatients presenting with AMI. After 1 year of follow-up, major adverse cardiac events(MACE) were recorded. A Cox proportional hazards model was used to calculate hazard ratios with 95% confidence intervals. We found that, compared with male groups, PCSK9 levels were higher in female patients not only for overall patients with AMI but also for patients with ST-elevation myocardial infarction (STEMI) (median: 273.6 [215.6–366.8] vs. 325.1 [247.5–445.3] ng/ml, P = 0.0136; 273.4 [215.6–369.7] vs. 317.1 [249.6–450.1], P = 0.0275, respectively). The cumulative incidence of cardiac death and 1-year MACE were significantly higher in the female group compared with male group (10% vs. 2.74%, P = 0.025; 15% vs. 4.11%, P = 0.0054, respectively). On multivariate Cox regression analysis, female sex, total triglyceride, glycosylated hemoglobin A, and homocysteic acid were independent risk factors of 1-year MACE. There was no significant correlation between PCSK9 and 1-year MACE in total AMI patients. In conclusion, PCSK9 levels and 1-year MACE were higher in women with AMI than in men with AMI, however, female sex but not PCSK9 were significant correlated with the 1-year MACE. The clinical implications of this finding are worthy of further investigations and must be confirmed in larger cohorts.

Although the prevalence of human immunodeficiency virus (HIV) decreased in the last decade worldwide, the number of deaths due to HIV/AIDS and communicable diseases including syphilis, hepatitis, and tuberculosis had dramatically increased in developing countries. Education and behavior are incredibly important factors to prevent these diseases’ spread. This study highlights the range of differences in knowledge, attitude, and behavior of 434 sexually active medical students towards HIV/AIDS and sexually transmitted infections (STIs). Because the surveyed population constitutes the forefront of healthcare providers and was originated from different area of the world, this is the first time a study sought to investigate the behavioral attitude of this group of population irrespective of the three levels of their academic and professional knowledge. Several factors including sociodemographic characteristics, sexual behavior, HIV/AIDS, and STIs related patterns play a key role in medical student attitude and behavior towards people infected with HIV/AIDS and STIs. Our findings add consistent value in prior studies which aimed to stop new infections and also imply further investigations on the management of the studied infections by medical students. The present study arouses much interest among participants and provides evidence of reinforcing medical students’ education on HIV/AIDS and STIs.

Evidence suggests that subclinical hypothyroidism (SCH) and thyroid autoimmunity (TAI) are associated with adverse pregnancy outcomes. This systematic review and meta-analysis was conducted to determine whether levothyroxine (LT4) supplementation would improve pregnancy outcomes among infertile women with SCH and/or TAI who underwent in vitro fertilization (IVF) or intracytoplastic sperm injection (ICSI). We searched databases of PubMed, EMBASE, Web of Science, Cochrane Controlled Trials Register databases, and Clinicaltrials.gov up to April 2018 to identify eligible studies. Studies that focused on the treatment effect of LT4 on pregnancy outcomes of women with SCH and/or TAI who underwent IVF/ICSI were included in the data synthesis. We only included randomized controlled trials (RCTs). Relative risks (RR) and 95% confidence intervals (CI) were calculated using a random-effects model to assess the results of pregnancy outcomes, including clinical pregnancy rate, miscarriage rate, live birth rate and preterm birth rate. Four published RCTs including 787 infertile couples undergoing IVF/ICSI were included in this meta-analysis. Notably, the study observed no significant associations of LT4 treatment with the clinical pregnancy rate (RR = 1.46, 95% CI: 0.86–2.48), live birth rate (RR = 2.05, 95% CI: 0.96–4.36), or preterm birth rate (RR = 1.13, 95% CI: 0.65–1.96). However, patients receiving LT4 supplementation had a significantly decreased miscarriage rate relative to those receiving a placebo or no treatment (RR = 0.51, 95% CI: 0.32–0.82). A further sub-group analysis showed that LT4 supplementation did not improve the miscarriage rates among patients with SCH (RR = 0.67, 95% CI: 0.39–1.15) or TAI (RR = 0.28, 95% CI: 0.07–1.06). Given its potential to reduce the miscarriage rate, LT4 supplementation is recommended for infertile women with SCH and/or TAI who are undergoing IVF/ICSI. However, additional population-based RCTs are needed to confirm this recommendation.

Li-Xia Hu,1,* Shi-Fu Hu,2,* Meng Rao,2,3 Jing Yang,2,4 Hui Lei,2,5 Zhuo Duan,6 Wei Xia,2,7 Changhong Zhu2,7 1Department of Histology and Embryology, Preclinical Medicine College, Xinxiang Medical University, Xinxiang,Henan, People’s Republic of China; 2Family Planning Research Institute, Tongji Medical College, Huazhong University of Science and Technology, Wuhan,Hubei, People’s Republic of China; 3Department of Reproduction and Genetics, the First Affiliated Hospital of Kunming Medical University, Kunming,Yunnan, People’s Republic of China; 4Department of Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou,Henan, People’s Republic of China; 5Department of Gynaecology and Obstetrics, Taikang Tongji Hospital, Wuhan,Hubei, People’s Republic of China; 6Dayu Medical Devices Co., Ltd., Jingzhou,Hubei, People’s Republic of China; 7Reproductive Medicine Center, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China *These authors contributed equally to this work Introduction: The physiologic safety of devices and materials intended for clinical implantation should be evaluated. This study, a logical extension of our previous work, aimed to investigate the safety of a novel contraceptive device, the copper/low-density polyethylene nanocomposite intrauterine device (nano-Cu/LDPE IUD), through studies of its potential toxicity after acute and subchronic administration in mice and rats. Methods: For the acute toxicity study, single 50mL/kg doses of nano-Cu/LDPE IUD extracts were administered to mice via intravenous or intraperitoneal injection. General behavioral adverse effects, mortality, and body weights were evaluated for up to 72hours. In the 13-week subchronic toxicity study, the nano-Cu/LDPE composite with 10-fold higher than the standard clinical dose was implanted subcutaneously into the dorsal skin of Wistar rats. The control group underwent a sham procedure without material insertion. Results: During all acute study observation times, the biologic reactions of the mice in the nano-Cu/LDPE group did not differ from those observed in the control group. The groups did not differ statistically in terms of body weight gain, and no macroscopic changes were observed in any organs. In the subchronic study, no clinical signs of toxicity or mortality were observed in either the nano-Cu/LDPE or control group during the 13-week period. The nano-Cu/LDPE composite did not cause any alterations in body weight, food consumption, hematologic and biochemical parameters, or organ weight relative to the control for any observed sample group. Histopathologic examinations of the organs revealed normal architecture, indicating that the inserted material did not cause morphologic disturbances in the rats. Conclusion: Overall, the results indicate that the nano-Cu/LDPE IUD did not induce systemic toxicity under experimental conditions of the recommended standard practices, suggesting that the novel material IUD is safe and feasible for future contraceptive applications. Keywords: intrauterine device, copper/low-density polyethylene nanocomposite intrauterine device, acute toxicity, subchronic toxicity

BACKGROUND Humanin has reportedly been expressed in testis and spermatozoa, but no study has yet reported its presence in human seminal plasma (SP). OBJECTIVE The aim of this study was to investigate the presence of humanin in human SP and to determine the correlation between humanin levels in SP/spermatozoa and sperm quality. MATERIALS AND METHODS Semen samples for SP/sperm humanin level measurement were collected from 164 patients who attended our andrology clinic for fertility evaluation. The localization of humanin in spermatozoa was evaluated using an immunofluorescence method, and SP/sperm humanin levels were measured with ELISA. Correlations between SP/sperm humanin levels and sperm parameters were analyzed. RESULTS Humanin was expressed in the midpiece of the spermatozoa. Humanin concentrations in the SP ranged from 24.4 to 285.1 pg/mL, with a median of 89.7 pg/mL. The SP humanin concentrations in patients with normospermia were significantly higher than those in patients with oligospermia (p

Objective This meta-analysis was aimed to evaluate the association between maternal physical activity before IVF/ICSI cycles and reproductive outcomes. Methods We searched databases of PubMed, EMBASE and Web of Science electronic databases, and ongoing trials up to November 2017 to identify studies that focused on the relationship between maternal physical activity before IVF/ICSI cycles and reproductive outcomes, including implantation rate, clinical pregnancy rate, miscarriage rate and live birth rate. Odds ratio (OR) with 95% confidence intervals, were calculated to assess the results of each outcome. Results Eight published studies encompassing 3683 infertile couples undergoing IVF/ICSI treatment were included into the analysis. There was an increasing, but not statistically significant, trend in implantation rate for physically active women when compared with physically inactive women (OR = 1.95, 95% CI 0.99–3.83, I 2 = 77%). No significant difference was found in miscarriage rate between physically active women and physically inactive women (OR = 0.76, 95% CI 0.41–1.44, I 2 = 49%). However, rates of clinical pregnancy and live births in physically active women were significantly higher than those in physically inactive women (OR = 1.96, 95% CI 1.40, 2.73, I 2 = 42% and OR = 1.95, 95% CI 1.06–3.59, I 2 = 82%, respectively). Subgroup analysis helped to confirm these results. Conclusions Female physical activity before IVF/ICSI cycles was associated with increased rates of clinical pregnancy and live births, whereas only a small but not statistically significant increase was found in implantation rate, and no effect was shown on miscarriage rate.

The aim of this study was to investigate whether sperm parameters can affect the pregnancy outcome of artificial intrauterine insemination with cryopreserved donor spermatozoon (AID). A total of 1355 couples received 2821 AID treatment cycles in the Reproductive Medicine Center of the Tongji Medical College between January 2010 and December 2013, and the data were collected and retrospectively analysed. The relationship between pre-freezing, post-thawing as well as optimised sperm parameters and AID pregnancy outcome was investigated. Clinical pregnancy rate and cumulated pregnancy rate were also calculated. A total of 728 cycles from 2821 treatment cycles achieved pregnancies, and cumulated pregnancy rate was 25.81%. Pre-freezing progressive sperm motility in pregnant cycles was higher than that in nonpregnant cycles (P = 0.001); logistic regression analysis also indicated that pre-freezing progressive sperm motility was the only parameter affecting pregnancy outcome (P = 0.0001). Our study also showed that the cumulated pregnancy rate increased progressively and reached a plateau after the fifth cycle. In conclusion, pre-freezing progressive sperm motility should be a valuable predictor for AID pregnancy outcome. Female fertility factors should be considered, or IVF/ICSI should be recommended when couples received more than 5 AID cycles without pregnancy.

Objectives: We recommend a new kind of spray made from eight kinds of traditional Chinese medicine, we aimed to investigate the safety and clinical efficacy of combined traditional Chinese medicine spray (TCMS) with premature ejaculation desensitization therapy (PEDT) for the treatment of primary premature ejaculation (PPE). Methods: A total of 90 patients with PPE were randomly assigned to receive TCMS, PEDT monotherapy or TCMS plus PEDT combination therapy for 6 weeks. Intravaginal ejaculation latency time (IELT) and Chinese index of sexual function for premature ejaculation (CIPE-5) were measured to evaluate the effect of each treatment. Results: Eighty six (86) participants completed the study voluntarily. Both IELT and CIPE-5 in these three groups increased after treatment when compared with baseline levels (p< 0.01). IELT and CIPE-5 after treatment in TCMS plus PEDT group were significantly higher than those in the other two groups (both p

Cold-inducible RNA-binding protein (CIRBP) is reduced by scrotal hyperthermia in cryptorchidism, varicocoele and heat treatment, but there is no direct evidence clarifying the relationship between CIRBP and spermatogenesis. The aim of this study was to investigate the expression of CIRBP in GC2-spd cells (a mouse spermatocyte cell line) before and after heat treatment, and to determine the effects of the downregulation or overexpression of CIRBP on spermatocyte cell proliferation and apoptosis. GC2-spd cells overexpressing CIRBP and GC2-spd cells in CIRBP was knocked down were constructed to investigate the function of CIRBP in cell proliferation and apoptosis using a cell counting kit-8 and flow cytometry respectively. In addition, proliferation and apoptosis were evaluated in GC2-spd cells that had been heated for 30 or 60min, and were analysed 12, 24, and 48h after heat treatment. Heat treatment clearly suppressed the proliferation of GC2-spd cells, and upregulation of CIRBP expression in GC2-spd cells promoted cell proliferation and decreased apoptosis before and after heat stress; in contrast, downregulation of CIRBP expression inhibited cell proliferation and increased apoptosis. These findings suggest that CIRBP exerts a protective effect against spermatogenic injury caused by heat stress.

Summary This prospective randomized clinical study is aimed to evidence the reproductive impairment of frequent scrotal heat exposure. A total of 20 normozoospermic subjects were randomly divided into two groups to undergo testicular warming in a 43 °C water bath 10 times, for 30 min each time; the subjects in group 1 underwent testicular warming for 10 consecutive days and those in group 2 once every 3 days. Sperm chromatin structure assay (SCSA), sperm mitochondrial membrane potential (MMP), apoptosis, and seminal plasma-soluble Fas (sFas) were analyzed before treatment and every 2 weeks after, for a total of 10 times. In group 1, some critical proteins involved in heat stress, hypoxia, structure, and function of sperm mitochondria and flagella were evaluated before hyperthermia and 2, 6, 10, and 16 weeks after hyperthermia. Both groups showed a reversible increase in the proportion of spermatozoa with a disrupted MMP (both p