Integrated MicroRNA and Secretome Analysis of Human Endometrial Organoids Reveal the miR-3194-5p/Aquaporin/S100A9 Module in Regulating Trophoblast Functions.

Successful placentation requires delicate communication between the endometrium and trophoblasts. The invasion and integration of trophoblasts into the endometrium during early pregnancy are crucial to placentation. Dysregulation of these functions is associated with various pregnancy complications, such as miscarriage and preeclampsia. The endometrial microenvironment has an important influence on trophoblast cell functions. The precise effect of the endometrial gland secretome on trophoblast functions remains uncertain. We hypothesized that the hormonal environment regulates the miRNA profile and secretome of the human endometrial gland, which subsequently modulates trophoblast functions during early pregnancy. Human endometrial tissues were obtained from endometrial biopsies with written consent. Endometrial organoids were established in matrix gel under defined culture conditions. They were treated with hormones mimicking the environment of the proliferative phase (Estrogen, E2), secretory phase (E2+Progesterone, P4), and early pregnancy (E2+P4+Human Chorionic Gonadotropin, hCG). miRNA-seq was performed on the treated organoids. Organoid secretions were also collected for mass spectrometric analysis. The viability and invasion/migration of the trophoblasts after treatment with the organoid secretome were determined by cytotoxicity assay and transwell assay, respectively. Endometrial organoids with the ability to respond to sex steroid hormones were successfully developed from human endometrial glands. By establishing the first secretome profiles and miRNA atlas of these endometrial organoids to the hormonal changes followed by trophoblast functional assays, we demonstrated that sex steroid hormones modulate aquaporin (AQP)1/9 and S100A9 secretions through miR-3194 activation in endometrial epithelial cells, which in turn enhanced trophoblast migration and invasion during early pregnancy. By using a human endometrial organoid model, we demonstrated for the first time that the hormonal regulation of the endometrial gland secretome is crucial to regulating the functions of human trophoblasts during early pregnancy. The study provides the basis for understanding the regulation of early placental development in humans.

Heat wave exposure and semen quality in sperm donation volunteers: A retrospective longitudinal study in south China.

BACKGROUND: Previous studies have suggested an association between non-optimum ambient temperature and decreased semen quality. However, the effect of exposure to heat waves on semen quality remains unclear. METHODS: Volunteers who intended to donate sperm in Guangdong provincial human sperm bank enrolled. Heat waves were defined by temperature threshold and duration, with a total of 9 definitions were employed, specifying daily mean temperature exceeding the 85th, 90th, or 95th percentile for at least 2, 3, or 4 consecutive days. Residential exposure to heat waves during 0-90 days before ejaculation was evaluated using a validated gridded dataset on ambient temperature. Association and potential windows of susceptibility were evaluated and identified using linear mixed models and distributed lag non-linear models. RESULTS: A total of 2183 sperm donation volunteers underwent 8632 semen analyses from 2018 to 2019. Exposure to heat wave defined as daily mean temperature exceeding the 95th percentile for at least 4 consecutive days (P95-D4) was significantly associated with a 0.11 (95% confidence interval [CI]: 0.03, 0.18) ml, 3.36 (1.35, 5.38) × 106/ml, 16.93 (7.95, 25.91) × 106, and 2.11% (1.4%, 2.83%) reduction in semen volume, sperm concentration, total sperm number, and normal forms, respectively; whereas exposure to heat wave defined as P90-D4 was significantly associated with a 1.98% (1.47%, 2.48%) and 2.08% (1.57%, 2.58%) reduction in total motility and progressive motility, respectively. Sperm count and morphology were susceptible to heat wave exposure during the early stage of spermatogenesis, while sperm motility was susceptible to exposure during the late stage. CONCLUSION: Heat wave exposure was significantly associated with a reduction in semen quality. The windows of susceptibility during 0-90 days before ejaculation varied across sperm count, motility, and morphology. Our findings suggest that reducing heat wave exposure before ejaculation may benefit sperm donation volunteers and those attempting to conceive.

Myd88 Signaling Is Involved in the Inflammatory Response in LPS-Induced Mouse Epididymitis and Bone-Marrow-Derived Dendritic Cells.

Epididymitis is an epididymal inflammation that may lead to male infertility. Dendritic cells (DCs) and myeloid differentiation primary response gene 88 (Myd88) were associated with epididymitis in rodents. However, the functions of Myd88 on epididymal DCs remain unclear. This study investigated the role of Myd88 in DCs for epididymitis. The Myd88 signaling pathway, phenotypes of DC subsets, and cytokines were investigated in lipopolysaccharide (LPS)-induced epididymitis in mice. CRISPR-Cas9 was used to knockout Myd88 in bone-marrow-derived dendritic cells (BMDCs) and immortalized mouse epididymal (DC2) cell line. In the vivo experiments, levels of the proinflammatory cytokines IL-1α, IL-6, IL-17A, TNF-α, IL-1ß, MCP-1, and GM-CSF, mRNA for MyD88 related genes, and the percentages of monocyte-derived DCs (Mo-DCs) were significantly elevated in mice with epididymitis. In the vitro experiments, LPS significantly promoted the apoptosis of BMDCs. In addition, the concentration of inflammatory cytokines in BMDCs and DC2s were increased in the LPS group, while decreasing after the knockout of Myd88. These findings indicate that Myd88 on DCs is involved in the inflammation of epididymitis in mice, which may be a potential target for better strategies regarding the treatment of immunological male infertility.

The Role of Mononuclear Phagocytes in the Testes and Epididymis.

The mononuclear phagocytic system (MPS) is the primary innate immune cell group in male reproductive tissues, maintaining the balance of pro-inflammatory and immune tolerance. This article aims to outline the role of mononuclear macrophages in the immune balance of the testes and epididymis, and to understand the inner immune regulation mechanism. A review of pertinent publications was performed using the PubMed and Google Scholar databases on all articles published prior to January 2021. Search terms were based on the following keywords: 'MPS', 'mononuclear phagocytes', 'testes', 'epididymis', 'macrophage', 'Mφ', 'dendritic cell', 'DC', 'TLR', 'immune', 'inflammation', and 'polarization'. Additionally, reference lists of primary and review articles were reviewed for other publications of relevance. This review concluded that MPS exhibits a precise balance in the male reproductive system. In the testes, MPS cells are mainly suppressed subtypes (M2 and cDC2) under physiological conditions, which maintain the local immune tolerance. Under pathological conditions, MPS cells will transform into M1 and cDC1, producing various cytokines, and will activate T cell specific immunity as defense to foreign pathogens or self-antigens. In the epididymis, MPS cells vary in the different segments, which express immune tolerance in the caput and pro-inflammatory condition in the cauda. Collectively, MPS is the control point for maintaining the immune tolerance of the testes and epididymis as well as for eliminating pathogens.

Association of exposure to residential greenness with semen quality: A retrospective longitudinal study of sperm donation volunteers in Guangdong province, China.

BACKGROUND: Exposure to residential greenness has been associated with benefits on certain reproductive health outcomes. However, its potential benefits on semen quality remain unknown. OBJECTIVES: To quantitatively explore the association between exposure to residential greenness and semen quality. METHODS: We investigated 9142 sperm donation volunteers who underwent 38,682 semen examinations at Guangdong provincial human sperm bank in China during 2016-2019. Exposure to residential greenness was assessed using mean daily Normalized Difference Vegetation Index (NDVI) at each subject's residential address with a 400 m buffer during 0-90 days before each semen collection. Multivariate linear mixed models and linear regression models were used to assess the association between exposure to residential greenness and semen quality. RESULTS: An interquartile range increase in exposure to residential greenness was significantly associated with a 0.034 (95% confidence interval [CI]: 0.005, 0.063) ml, 4.06 (95% CI: 0.76, 7.37) × 106, and 0.32% (95% CI: 0.22%, 0.41%) increase in semen volume, total sperm number, and normal forms, respectively; similar trends were observed across quartiles of exposure to residential greenness (all p-values for liner trend <0.05 except for semen volume). The association of greenness exposure with semen volume and total sperm number was stronger in subjects 18-25 years, while the association with normal forms was stronger in subjects 26 years or older. The association for sperm concentration, total sperm number, and normal forms were stronger in cool season, while the association for semen volume was stronger in warm season. CONCLUSION: We found that exposure to residential greenness was significantly associated with higher semen quality. Further studies are warranted to determine the causality of the association and its underlying mechanisms.

[Management system and development strategy of quality Chinese medicine].

The development of quality Chinese medicine is an important way to improve the quality of Chinese medicine, and ensure the safety and effectiveness of Chinese medicine. This article systematically elaborates the definition, classification, standard and mana-gement certification strategy of quality Chinese medicine. We present the quality Chinese medicine which is higher quality than that of eligible Chinese medicine based on quality control standards. Quality Chinese medicine is strictly in accordance with management procedures, likely GAP and GMP et al, during the productive process, which quality indicators is higher than that of the current relevant national quality standards, such as Chinese Pharmacopoeia(ChP) et al; its limited indicators such as exogenous pollutants and endogenous toxic substances are lower than that of the current relevant national quality standards, likely ChP et al; meanwhile these Chinese herbal medicine, medicinal pieces, patent medicines, and health products and foods with Chinese medicine raw materials are been certificated by quality Chinese medicine. At the same time, this article systematically expounds the five major management systems of quality Chinese medicine, including technical training management for practitioners, productive process management, standard mana-gement, quality inspection and certification management, and product traceability management. And we put forward strategies to improve the supervision and management system, and promote the standardization and development of quality Chinese medicine by improving the technical management system of quality Chinese medicine, strengthening the quality management system and six sigma(6σ) management in the company. These strategies will provide a reliable basis and effective way to improve the quality of Chinese medicine.

CCL20-CCR6 axis directs sperm-oocyte interaction and its dysregulation correlates/associates with male infertility‡.

The interaction of sperm with the oocyte is pivotal during the process of mammalian fertilization. The limited numbers of sperm that reach the fallopian tube as well as anatomic restrictions indicate that human sperm-oocyte encounter is not a matter of chance but a directed process. Chemotaxis is the proposed mechanism for re-orientating sperm toward the source of a chemoattractant and hence to the oocyte. Chemokines represent a superfamily of small (8-11 kDa), cytokine-like proteins that have been shown to mediate chemotaxis and tissue-specific homing of leukocytes through binding to specific chemokine receptors such as CCRs. Here we show that CCR6 is abundantly expressed on human sperms and in human testes. Furthermore, radioligand-binding experiments showed that CCL20 bound human sperm in a specific manner. Conversely, granulosa cells of the oocyte-surrounding cumulus complex as well as human oocytes represent an abundant source of the CCR6-specific ligand CCL20. In human ovaries, CCL20 shows a cycle-dependent expression pattern with peak expression in the preovulatory phase and CCL20 protein induces chemotactic responses of human sperm. Neutralization of CCL20 in ovarian follicular fluid significantly impairs sperm migratory responses. Conversely, analyses in infertile men with inflammatory conditions of the reproductive organs demonstrate a significant increase of CCL20/CCR6 expression in testis and ejaculate. Taken together, findings of the present study suggest that CCR6-CCL20 interaction may represent an important factor in directing sperm-oocyte interaction.

Platelet-activating factor induces acrosome reaction via the activation of extracellular signal-regulated kinase in human spermatozoa.

Platelet-activating factor (PAF) affects capacitation, acrosome reaction and fertilisation potential of spermatozoa. This study investigated the underlying mechanism(s) through which PAF regulated sperm function. Our data demonstrated that PAF dose-dependently induced, whilst lyso-PAF (PAF precursor) showed no effect on acrosome reaction of capacitated human spermatozoa. Treatment with PAF for 90 min enhanced tyrosine phosphorylation and expression of extracellular signal-regulated protein kinases (ERK) 1 and 2 in human spermatozoa. Moreover, pre-treatment with the ERK inhibitor U0126 significantly and dose-dependently suppressed PAF-induced acrosome reaction. Therefore, PAF may be actively involved in the modulation of sperm acrosome reaction by interacting with ERK. The role of PAF in fertilisation warrants further investigation.

A randomised trial comparing conventional semen parameters, sperm DNA fragmentation levels and satisfaction levels between semen collection at home and at the clinic.

The aim of the randomised trial was to compare conventional semen parameters, sperm DNA fragmentation levels and satisfaction levels between semen samples collected at home and at the clinic. We recruited 110 men with a history of infertility for at least 1 year from the outpatient andrology clinic. Each man collected two semen samples, one at home and one at the clinic. Men were randomly assigned into the home first (n = 55) or clinic first (n = 55) groups. The primary outcome was sperm concentration. There was no significant difference in sperm concentration, sperm DNA fragmentation levels or other conventional semen parameters between home first and clinic first samples (p > .05), while satisfaction levels were significantly higher for home first samples (p < .01). Consistent results were obtained when comparing home-collected and clinic-collected samples within individuals. Men can be offered the option to collect semen samples at home for examination or assisted reproduction without compromising semen quality, especially for those with difficulty in producing semen samples at the clinic.

Human spermatozoa of male patients with subfertility express the interleukin-6 receptor.

Male subfertility has been associated with bacterial infections and chronic inflammation. In this context, several studies investigated cytokine levels in seminal plasma, whereas interleukin-6 (IL-6) appears to be crucial. However, little is known about its receptor, the IL-6R expression on human spermatozoa. Thus, the aim of the present study was to screen spermatozoa for IL-6R expression and to identify its localisation. Semen samples of 137 patients (median age 37.69, SD ± 7.82) with subfertility were analysed. Sperm analysis including determination of IL-6 was performed following the World Health Organization criteria. Also, flow cytometry was performed for sperm IL-6R expression. IL-6R+ cells were used for immunofluorescence staining to identify receptor localisation. The results showed positive staining for IL-6R in the midpiece of spermatozoa. Furthermore, a significant correlation between sperm IL-6R expression, seminal plasma IL-6 and total sperm count could be demonstrated, whereas a negative correlation was observed in sperm IL-6R expression and motility. However, no statistical significance could be observed between IL-6R expression, vitality and morphology. Moreover, incubation of spermatozoa with IL-6 led to a slight but significant decrease in motility after 24 hr. These data suggest that IL-6R expression may play a role in impaired sperm function during inflammation.

T Lymphocytes and Testicular Immunity: A New Insight into Immune Regulation in Testes.

The immune privilege of the testes is necessary to prevent immune attacks to gamete-specific antigens and paternal major histocompatibility complex (MHC) antigens, allowing for normal spermatogenesis. However, infection and inflammation of the male genital tract can break the immune tolerance and represent a significant cause of male infertility. Different T cell subsets have been identified in mammalian testes, which may be involved in the maintenance of immune tolerance and pathogenic immune responses in testicular infection and inflammation. We reviewed the evidence in the published literature on different T subtypes (regulatory T cells, helper T cells, cytotoxic T cells, γδ T cells, and natural killer T cells) in human and animal testes that support their regulatory roles in infertility and the orchitis pathology. While many in vitro studies have indicated the regulation potential of functional T cell subsets and their possible interaction with Sertoli cells, Leydig cells, and spermatogenesis, both under physiological and pathological processes, there have been no in situ studies to date. Nevertheless, the normal distribution and function of T cell subsets are essential for the immune privilege of the testes and intact spermatogenesis, and T cell-mediated immune response drives testicular inflammation. The distinct function of different T cell subsets in testicular homeostasis and the orchitis pathology suggests a considerable potential of targeting specific T cell subsets for therapies targeting chronic orchitis and immune infertility.

In vitro chemokine (C-C motif) receptor 6-dependent non-inflammatory chemotaxis during spermatogenesis.

BACKGROUND: Chemokine (C-C motif) receptor 6 (CCR6) is present in sperm and plays a significant role in sperm motility and chemotaxis acting in the reproductive tracts. However, the expression and functional significance of CCR6 in testis are still poorly understood, especially in the process of spermatogenesis. METHODS AND RESULTS: CCR6 was expressed in spermatogenic cell lines and its expression was shown in an age-dependent upregulation manner from puberty to adulthood in mouse testis. Immunostaining results confirmed the localization of CCR 6 in testis. Further chemotaxis assays demonstrated that spermatogenic cells GC-1 and -2 exhibited a directional movement toward CCR6-specific ligand such as CCL20 or Sertoli cells in vitro. CONCLUSIONS: The present findings indicate that CCR6 is involved in the chemotaxis of spermatogenic cells in vitro and promotes chemotaxis under non-inflammatory conditions during normal spermatogenesis.

Uropathogenic Escherichia coli causes fibrotic remodelling of the epididymis.

Despite antibiotic treatment, up to 40% of patients have impaired fertility after epididymitis due to serovars of Escherichia coli, a frequent pathogen. The reasons for infertility are unclear, but it may result from epididymal duct obstruction. To determine whether E. coli infection of the epididymis causes obstruction due to fibrosis, and to identify the key mediators, tissues from patients with epididymitis were assessed. Additionally, epididymitis was induced with uropathogenic E. coli (UPEC) or commensal serovars in wild-type and MyD88(-/-) mice, which are relatively unresponsive to bacterial pathogens. Epididymal organ cultures were treated with activin A and bacteria and their histology and levels of cytokines and fibrosis markers were analysed. Patients with epididymitis showed severe fibrosis of the epididymal duct. In mice, UPEC infection also caused fibrosis and ductal obstruction in the cauda epididymis. Levels of mRNA for fibrotic markers (α-smooth muscle actin, fibronectin) and cytokines (activin A, TNFα, IL-1α, IL-1ß, IL-6) and total collagen levels were significantly elevated. This fibrotic response was blunted by the loss of MyD88. Activin A induced fibrosis in cultured epididymis, which was inhibited by the activin-binding protein follistatin. In summary, bacterial epididymitis causes fibrosis and obstruction. The milder tissue damage in Myd88(-/-) UPEC epididymitis highlights the importance of the host response to infection in causing epididymal damage. Elevated levels of activin A in vivo and fibrotic remodelling elicited by activin A in vitro indicate that this cytokine is a potential target for supplementary treatment to antibiotic therapy. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Inverse Association between Ambient Sulfur Dioxide Exposure and Semen Quality in Wuhan, China.

Evidence concerning the association between ambient gaseous air pollutant exposures and semen quality is sparse, and findings in previous studies remain largely inconsistent. We enrolled 1759 men and performed 2184 semen examinations at a large reproductive medical center in Wuhan, China, between 2013 and 2015. Inverse distance weighting interpolation was performed to estimate individual exposures to SO2, NO2, CO, and O3 during the entire period (lag 0-90 days) and key periods (lag 0-9, 10-14, 70-90 days) of sperm development. Linear mixed models were used to analyze exposure-response relationships. SO2 exposure with 0-90 days lag was significantly associated with monotonically decreased sperm concentration (ß for each interquartile range increase of exposure: -0.14; 95% CI: -0.23, -0.05), sperm count (-0.21; -0.30, -0.12) and total motile sperm count (-0.16; -0.25, -0.08). Significant associations were observed for total and progressive motility only when SO2 exposure was at the highest quintile (all Ptrend < 0.05). Similar trends were observed for SO2 exposure with 70-90 days lag. NO2, CO, or O3 exposure was not significantly associated with semen quality. Our results suggest that ambient SO2 exposure adversely affects semen quality and highlight the potential to improve semen quality by reducing ambient SO2 exposure during early stages of sperm development.

Promoter targeted bisulfite sequencing reveals DNA methylation profiles associated with low sperm motility in asthenozoospermia.

STUDY QUESTION: Is there an association between sperm DNA methylation profiles and asthenozoospermia? SUMMARY ANSWER: DNA methylation, at specific CpGs but not at the global level, was significantly different between low motile sperm cells of asthenozoospermic individuals and high motile sperm cells of normozoospermic controls. WHAT IS KNOWN ALREADY: Aberrant DNA methylation, both globally and restricted to a specific gene locus, has been associated with male infertility and abnormal semen parameters. STUDY DESIGN, SIZE, DURATION: This was a case-control study investigating the differences in DNA methylation at CpGs in promoter regions between high and low motile sperm cells from eight normozoospermic controls and seven asthenozoospermic patients. PARTICIPANTS/MATERIALS, SETTING, METHODS: The liquid hybridization capture-based bisulfite sequencing method was used to determine DNA methylation at CpGs in promoter regions. The global inter-individual and intra-individual methylation variability were estimated by evaluating the methylation variance between and within different motile sperm fractions from the same or different individuals. Asthenozoospermia-associated differentially methylated or variable CpGs and differentially methylated regions were identified by comparing the DNA methylation of high motile sperm cells from normozoospermic controls with that of low motile sperm cells from asthenozoospermic patients. MAIN RESULTS AND THE ROLE OF CHANCE: In this study, we determined the global DNA methylation level (24.7%), inter-individual variance (14.4%) and intra-individual differences between high and low motile sperm fractions (3.9%). We demonstrated that there were no statistically significant differences in either the global DNA methylation level or global methylation variability between sperm from men with normozoospermia or asthenozoospermia. Between high motile sperm from men with normozoospermia and low motile sperm from men with asthenozoospermia, we identified 134 differentially methylated CpGs, 41 differentially methylated regions and 134 differentially variable CpGs. The genomic distribution patterns of the differential methylation spectrum suggested that gene expression may be affected in low motile sperm cells of asthenozoospermic patients. Finally, through a functional analysis, we detected 16 differentially methylated or variable genes that are required for spermatogenesis and sperm motility or dominantly expressed in testis. LIMITATIONS, REASONS FOR CAUTION: The sample size in this study was limited, although the participants in the two groups were carefully selected and well matched. Our results must be verified in larger cohorts with the use of different techniques. Furthermore, our results were descriptive, and follow-up studies will be needed to elucidate the effect of differential methylation profiles on asthenozoospermia. WIDER IMPLICATIONS OF THE FINDINGS: Our study identified asthenozoospermia-associated DNA methylation profiles and proposed a list of genes, which were suggested to be involved in the regulation of sperm motility through an alteration of DNA methylation. These results will provide promising clues for understanding the effect of DNA methylation on sperm motility and asthenozoospermia. STUDY FUNDING/COMPETING INTERESTS: This study was funded primarily by the National Natural Science Foundation of China, Shenzhen Project of Science and Technology and the National Basic Research Program of China. The authors have no competing interests.

Expressions of miR-15a and its target gene HSPA1B in the spermatozoa of patients with varicocele.

Hyperthermia and oxidative stresses are the two central elements contributing to varicocele-related sperm damage. Growing evidence indicates that microRNAs (miRNAs) are involved in the regulation of the heat and oxidative stress responses. In this study, we analyzed the expressions of several stress-related miRNAs in the sperm and found that the expression of miR-15a was significantly decreased in patients with varicocele compared with the control. Furthermore, miR-15a repressed the expression of HSPA1B, which is a typical stress-induced chaperone protein, through directly binding its 3'-UTR. The expressions of miR-15a and HSPA1B exhibited an inverse correlation in sperm. Our results provide a valuable insight into the varicocele-related sperm impairment and male infertility, and may help to develop potential therapeutic targets and novel biomarkers for male infertility.

Identification of Hsf1 as a novel androgen receptor-regulated gene in mouse Sertoli cells.

Androgen signaling plays a crucial role in spermatogenesis, yet few downstream targets for this signaling pathway have been identified. In the current study, we found that the expression of heat-shock transcription factor 1 (Hsf1) was increased in the testes of Sertoli cell-selective androgen receptor knockout (S-AR(-/y) ) mice compared with wild-type mice by quantitative real-time PCR, and the expression of HSF1 in the S-AR(-/y) Sertoli cells was significantly increased, based on immunofluorescence analysis. In vitro cell-culture studies showed that testosterone repressed the expression of Hsf1 in TM4 cells, a mouse Sertoli cell line. Moreover, a luciferase assay, electrophoretic mobility shift assay, and chromatin immunoprecipitation assay showed that testosterone repressed Hsf1 expression by facilitating the binding of androgen receptor to the Hsf1 promoter. Our experiments also demonstrated that testosterone-mediated inhibition of Hsf1 transcription down-regulated the expression of heat-shock proteins HSP105 and HSP60. Taken together, these results reveal that Hsf1 is a novel target of androgen receptor in mouse Sertoli cells, and testosterone and its receptor regulate the process of spermatogenesis partially by inhibiting Hsf1 expression.

Immunodeviation towards T cell-mediated immune response in the testes of LPS-induced mouse epididymo-orchitis.

The testicular consequences of acute epididymo-orchitis remain largely unelucidated in long-term damage, which might be a neglected factor for male infertility. In this study, the differential phenotype of testicular immune cell subpopulations in lipopolysaccharide (LPS)-induced mouse epididymo-orchitis were analyzed by flow cytometry on day 1, day 7, and day 28. The number of macrophages, neutrophils, and myeloid-derived suppressor cells (MDSCs) steadily decreased in the testes with inoculation. Total F4/80-CD11c+ dendritic cells (DCs) maintained a relatively stable level, whereas conventional type 1 dendritic cells (cDC1) increased gradually from day 1 to day 28. There was a lower number of CD4+ and CD8+ T cells at day 1 and day 7, and they had similar results with a ceiling level at day 28. The testes displayed a higher level of CD3+ T cells but a lower frequency of macrophages, cDC2, and neutrophils at 28 days post-inoculation compared with the epididymis. In summary, our data indicates acute epididymo-orchitis could lead to long-term damage in the testes, which is characterized by CD3+ T cell (including CD4+ and CD8+ T cells)-mediated immune responses.

Association between central obesity and semen quality: A cross-sectional study in 4513 Chinese sperm donation volunteers.

BACKGROUND: General obesity classified by body mass index has been linked to a reduction in semen quality; however, evidence on the adverse effect of central obesity on semen quality remains limited. OBJECTIVES: To investigate the association between central obesity and semen quality. MATERIALS AND METHODS: We conducted a cross-sectional study of 4513 sperm donation volunteers in Guangdong Provincial Human Sperm Bank during 2018-2021. Three central obesity indicators, including waist circumference, waist-to-hip ratio, and waist-to-height ratio, were measured using a multi-frequency bioelectrical impedance analysis for each subject. Semen analysis was conducted according to the World Health Organization laboratory manual for the examination and processing of human semen 5th edition. Linear regression models and unconditional logistic regression models were used to quantify the association between central obesity and semen parameters. RESULTS: With adjustment for age, race, education level, marital status, fertility status, occupation, year of semen collection, abstinence period, ambient temperature, and relative humidity, central obesity defined as waist circumference ≥90 cm, waist-to-hip ratio ≥0.9, or waist-to-height ratio ≥0.5 was significantly associated with a 0.27 (95% confidence interval: 0.15, 0.38) mL, 14.47 (3.60, 25.34) × 106 , 7.06 (0.46, 13.76) × 106 , and 6.80 (0.42, 13.18) × 106 reduction in semen volume, total sperm number, total motile sperm number, and total progressive motile sperm number, respectively, and a 53% (10%, 112%) increase in odds of below the World Health Organization 2010 reference value for semen volume. These associations did not significantly vary across age. Similar results were observed for central obesity defined using each of the three indicators, except that subjects with a waist circumference ≥90 cm had a slightly higher total motility (estimated change: 1.30%; 95% confidence interval: 0.27%, 2.34%) and progressive motility (estimated change: 1.27%; 95% confidence interval: 0.23%, 2.31%). DISCUSSION AND CONCLUSION: We found that central obesity was significantly associated with a reduction in semen volume, total sperm number, total motile sperm number, and total progressive motile sperm number. Future studies are warranted to confirm our results in other regions and populations.

From Waterloo to the Great Wall: A retrospective, multicenter study on the clinical practice and cultural attitudes in the management of premature ejaculation, in China.

Premature ejaculation (PE), despite its wide prevalence, is largely underdiagnosed and undertreated. Being a multifactorial dysfunction with strong cultural characteristics, PE requires skillful attitudes in the psychosexological support, necessary to manage the patient's and the couple's expectations, as well as in the medical treatment. Dapoxetine is a short-acting selective serotonin reuptake inhibitor approved for use in lifelong and acquired PE in a number of countries. Opinions, not always generated by the evidence-based medicine, impacted the attitudes of Western andrologists, as a nocebo effect which produced a drug's Waterloo, characterized by low prescription rates much more built on the patients' and doctors' expectations than on costs, side effects, and efficacy. In the present study, we retrospectively reviewed real-life data from eight Andrology and Sexual Medicine Public Centers in China to assess the prevalence of PE among attending patients, its association with erectile dysfunction, its subtype, and the proposed treatments. In 2019, among 156,486 patients coming to the centers, 32,667 visits having PE as the chief complaint were performed (20.9%). Almost all patients received treatment prescriptions (32,641 patients, 99.92%); 23,273 patients came back for a follow-up visit in the subsequent 12 months (71.2% of those who initially received treatment). Dapoxetine, either alone or in combination with another therapy, was the most prevalent treatment, prescribed to 22,767 patients (69.7% of treated patients), followed by traditional Chinese medicine (TCM) (39.4%). At follow-up, 8174 patients were unsatisfied with treatment, and a new treatment was proposed (35.12%). Dapoxetine was the best treatment, with an overall 27.1% switching rate when used either alone or in combination: Although the switching rate for Dapoxetine alone was 44.2%, the association of the same drug with psychotherapy resulted in much lower rates (19.5%) and reached a minimum of 12% when also combined with TCM demonstrating how cultural aspects and medical attitudes may dramatically impact on the therapy of a multifaceted, complex, and culture-grounded sexual symptom such as PE. In conclusion, taking switching rates as surrogate markers of treatment failure, this real-life study-the largest in the field-shows that in a more patient-oriented (as in Chinese medical culture), and less symptom-oriented (as in Western medical attitudes), Dapoxetine is a successful treatment for PE patients, with higher reliability when used alone or as part of combined and integrated therapies.