P-030 ACE2 receptor and its isoform short-ACE2 are expressed on human spermatozoa

STUDY QUESTION: Do human spermatozoa express angiotensin-converting enzyme 2 (ACE2) receptor? What would be its localization? SUMMARY ANSWER: Human spermatozoa express uniformly ACE2 on the sperm head and the flagellum. Moreover, the short-ACE2 isoform is concentrated on the post-acrosomal region and midpiece. WHAT IS KNOWN ALREADY: The Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2) infection is generating important concerns regarding not only the possible consequences on the respiratory system, but also on other organs, including the reproductive system. ACE2 is considered the main point of entry for the SARS-CoV-2 within the cells through the binding with the spike protein on the virus surface. Furthermore, ACE2 is expressed in human testes cells including Leydig cells, Sertoli cells and spermatogonia. However, to date, the expression and location of ACE2 in mature human spermatozoa has not been investigated yet. STUDY DESIGN, SIZE, DURATION: This was an in vitro study for the evaluation of the expression and immune-localization of full-length ACE2 and its isoform, short-ACE2, in human spermatozoa. Thirthyfour non-immunized healthy normozoospermic volunteers were enrolled in the study. The study was conducted from May to December 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: Semen samples were collected by masturbation from non-immunized healthy normozoospermic voluntaries. Motile sperm suspensions were obtained by swim-up procedure. The expression of ACE2 was assessed by Western-blot analysis, while the immune-localization of ACE2 was evaluated by immune-cytochemical analysis under confocal microscopy. Flow-cytometry experiments were also performed to assess the surface protein expression on a large number of cells. MAIN RESULTS AND THE ROLE OF CHANCE: The Western-blot analysis of sperm extracts demonstrated two specific bands, one of approximately 120 KDa, corresponding to the glycosylated full-length ACE2, and a second one of approximately 52 KDa, the molecular weight of the protein recently termed short-ACE2. The immune-cytochemical analysis showed a uniformly localization of full-length ACE2 along both the sperm head and the flagellum, whereas the short isoform was preferentially located in the post-acrosomal region of the sperm head and the midpiece. At the flow cytometer, semen samples displayed a wide between-subject variability both in the percentage of ACE2-positive spermatozoa and the density of protein surface expression. LIMITATIONS, REASONS FOR CAUTION: Further studies are needed to determine whether short-ACE2 is a cleavage product from the full-length protein or if it is originated during spermatogenesis. Moreover, the role and the interaction of ACE2 with SARS-CoV-2 in human spermatozoa should be clarified to evaluate the possible impact of the virus on sperm biology. WIDER IMPLICATIONS OF THE FINDINGS: Since mature spermatozoa are transcriptionally silent and SARS-CoV-2 is an RNA virus, it is unlikely that the virus could affect sperm biology by replicating itself. Nevertheless, the potential effects related to modifications of the sperm membrane or interaction with other receptors or specific proteins cannot be ruled out. TRIAL REGISTRATION NUMBER: not applicabl

ACE2 Receptor and Its Isoform Short-ACE2 Are Expressed on Human Spermatozoa

Angiotensin-converting enzyme 2 (ACE2) is a protein widely expressed in numerous cell types, with different biological roles mainly related to the renin-angiotensin system. Recently, ACE2 has been in the spotlight due to its involvement in the SARS-CoV-2 entry into cells. There are no data available regarding the expression of ACE2 and its short-ACE2 isoform at the protein level on human spermatozoa. Here, protein expression was demonstrated by western blot and the percentage of sperm displaying surface ACE2 was assessed by flow cytometry. Immunocytochemistry assays showed that full-length ACE2 was mainly expressed in sperm midpiece, while short ACE2 was preferentially distributed on the equatorial and post-acrosomal region of the sperm head. To our knowledge, this is the first study demonstrating the expression of protein ACE2 on spermatozoa. Further studies are warranted to determine the role of ACE2 isoforms in male reproduction

Views and Experiences of Sex, Sexuality and Relationships Following Spinal Cord Injury: A Systematic Review and Narrative Synthesis of the Qualitative Literature

Research examining the effects of spinal cord injury on sexuality has largely focused on physiological functioning and quantification of dysfunction following injury. This paper reports a systematic review of qualitative research that focused on the views and experiences of people with spinal cord injury on sex and relationships. The review addressed the following research question: What are the views and experiences of people with spinal cord injury of sex, sexuality and relationships following injury? Five databases were relevant and employed in the review: CINAHL (1989-2016 only), PsychInfo, PubMed, Scopus and Web of Science, for research published between 1 January 1980 and 30 November 2019. After removing duplicates, 257 records remained and were screened using a two-stage approach to inclusion and quality appraisal. Following screening, 27 met the criteria for inclusion and are reported in the paper. The review includes studies from fifteen countries across five continents. Two main approaches to data analysis summary and thematic synthesis were undertaken to analyze the qualitative data reported in the papers. The analysis revealed four main themes: sexual identity; significant and generalized others, sexual embodiment; and; sexual rehabilitation and education

Prevalence of anti-sperm antibodies and relationship of degree of sperm auto-immunization to semen parameters and post-coital test outcome: a retrospective analysis of over 10 000 men

STUDY QUESTION: What is the prevalence and the relationship of anti-sperm antibodies (ASA), screened by means of IgG-mixed antiglobulin reaction (MAR) test, to semen quality and post-coital test (PCT) outcome?SUMMARY ANSWER: A 100% positive IgG-MAR test, detected in 2% of the study population, was associated with lower sperm output and progressive motility, and was the sole determinant of higher prevalence of a negative PCT outcome.WHAT IS KNOWN ALREADY: Although ASA may affect sperm fertilizing ability and the IgG-MAR test is recommended by the World Health Organization (WHO) as an integral part of semen analysis for screening the occurrence of ASA, the prevalence and clinical relevance of positive MAR test results remain controversial.STUDY DESIGN, SIZE, DURATION: A retrospective analysis of 12 296 consecutive men who attended a university/hospital andrology clinic for the evaluation of fertility potential was carried out.PARTICIPANTS/MATERIALS, SETTING, METHODS: Immunological screening with the IgG-MAR test was performed on all ejaculates as an integral part of semen analysis. Positive samples (>= 10%) were further tested for IgA-ASA. The prevalence of positive IgG-MAR tests results, along with the relationship of the degree of sperm auto-immunization to semen parameters and PCT outcome, were analyzed.MAIN RESULTS AND THE ROLE OF CHANCE: After excluding semen samples showing azoospermia or severe oligo-asthenozoospermia, the prevalence of a positive IgG-MAR test in the remaining 10 025 men was 4%, 3.4% and 2%, with 10%, 50% and 100% thresholds, respectively. The 100%-positive MAR tests exhibited significantly higher consistency over time, and were significantly associated with higher prevalence of a mixed pattern (i.e. when the majority of sperm exhibited beads attached on both the head and along the tail) of positivity as well as with the concomitant occurrence of IgA-ASA. Additionally, the 100%-positive MAR tests were significantly associated with a lower median value of the total number of spermatozoa and progressive motility, compared to samples with a lower degree of positivity or negative samples. In the PCT performed in 120 couples, where ASA were detected in the male partner, the 100%-positive MAR tests were significantly associated with a higher prevalence of negative PCT outcome, in comparison to the lower degree of positivity, independent of, and without any significant contribution from, other determinants (semen and cervical mucus quality).LIMITATIONS, REASONS FOR CAUTION: Only surrogate infertility-related end-points were analyzed in the present study. However, since the impairment of sperm penetration through the cervical mucus represents the primary mechanism of ASA-interference with fertility, PCT outcome may represent a suitable clinical end-point.WIDER IMPLICATIONS OF THE FINDINGS: The present study, being the largest reported to date, provides a reliable estimate of ASA prevalence. Moreover, it indicates that a 50%-positive MAR test, which is suggested by WHO as the clinically-relevant threshold, also includes patients with a degree of sperm auto-immunization that contributes to couple infertility only in the presence of other causal factors; conversely, the 100%-positive MAR test can represent the sole determinant of couple infertility, as it was the sole significant predictor of the highly prevalent negative PCT outcome

Thyroid autoimmunity and risk of post-partum depression: a systematic review and meta-analysis of longitudinal studies

The aim of this study was to systematically investigate whether, and to what extent, the detection of thyroid autoimmunity during pregnancy and in the weeks after childbirth is associated with an increased risk of developing post-partum depression (PPD), a condition associated with possible adverse outcomes for both mother and offspring. We performed a systematic review and meta-analysis of longitudinal studies, assessing the incidence of PPD in women with and without anti-thyroperoxidase antibody (TPOAb) positivity

Sirtuins in gamete biology and reproductive physiology : emerging roles and therapeutic potential in female and male infertility

Background: Sirtuins (SIRT1-7) are a family of NAD+-dependent deacetylases that catalyze post-translational modifications of proteins. Together, they respond to metabolic challenges, inflammatory signals or hypoxic/oxidative stress, and are associated with aging and longevity. The role of Sirtuins in the regulation of fertility emerged in 2003 when a defective reproductive phenotype was observed in SIRT1-null mice. Although studies on Sirtuins in reproductive biology have been increasing in the last years, a recent comprehensive update on this issue is still lacking. Objective and rationale: This review is aimed to provide knowledge on the activation mechanism and cellular role of Sirtuins and to give an update of the rapid development of Sirtuin research in female and male reproduction under physiological and pathological conditions. The final goal is to assess whether strategies aimed to improve Sirtuin expression or activity could have therapeutic potential for infertility associated with polycystic ovarian syndrome (PCOS), endometriosis, diabetes, xenobiotic stress and aging. Search methods: The MEDLINE database was examined for peer-reviewed original articles. The following keywords were searched: 'Sirtuin', 'ovary', 'oocyte', 'ovarian follicle', 'embryo', 'endometrium', 'sperm' and 'testis'. These keywords were combined with other search phrases relevant to the topic. Outcomes: Our knowledge of Sirtuins in reproductive functions has grown exponentially over the last few years. The majority of the work carried out so far has focused on SIRT1 with a prevalence of studies on female reproduction. Numerous studies have provided evidence that down-regulation of SIRT1 is associated with physiological or pathological reduction of ovarian reserve. SIRT1 has also been shown to regulate proliferation and apoptosis in granulosa cells whereas SIRT3 was found to promote luteinisation. Biochemical modulation of Sirtuin activity has led to discoveries of the roles of SIRT1, SIRT2, SIRT3 and SIRT6 in improving the competence of oocytes grown or matured in vitro in humans and animal models. Recently, SIRT1, SIRT2 and SIRT3 have emerged as protectors of oocyte against postovulatory aging. Transgenic models provide strong evidence that SIRT1 is involved in spermatogenesis by influencing specific functions of male germ cell, Sertoli cells and Leydig cells. When our attention moves to post-fertilization events, maternally derived SIRT3 appears crucial in the protecting early embryos against stress conditions. Finally, increasing SIRT1 activity may have the potential to ameliorate fertility in PCOS, diabetes, endometriosis, xenobiotic stress and aging. Overall, these effects have been ascribed to Sirtuin-mediated regulation of energy homoeostasis, mitochondrial biogenesis, chromatin remodelling and protection against oxidative stress. Wider implications: The present review provides challenges and opportunities to stimulate research and exploit Sirtuin-based signalling as diagnostic tools and potential targets for therapeutic applications in reproductive medicine

Relationship between leukocytospermia, reproductive potential after assisted reproductive technology, and sperm parameters: a systematic review and meta-analysis of case–control studies

Background The association of leukocytospermia with male fertility is still under debate. Objective To evaluate the impact of leukocytospermia (>= 1 x 10(6) white blood cells/mL of semen, according to the World Health Organization) in men attending a fertility clinic for couple subfertility, on fertility outcomes after assisted reproductive technology (ART) and on semen quality. Materials and Methods A systematic review with meta-analysis of case-control studies reporting mean +/- standard deviation for values of different seminal parameters (sperm concentration, progressive motility, sperm morphology, sperm DNA fragmentation, semen volume, and Ph) and fertilization rate (FR), or the odds ratio (OR) for clinical pregnancy rate (PR) per cycle after ART in leukocytospermic and non-leukocytospermic patients was performed. A literature search was carried out in MEDLINE and SCOPUS for English-language studies published till June 2018. Results Twenty-eight case-controlled retrospective studies met the inclusion criteria, comparing fertility outcomes after ART or semen parameters in men with or without leukocytospermia. FR and PR after ART were not significantly different in the two groups. Leukocytospermic samples showed a lower sperm concentration (pooled SMD = -0.14; 95% CI: -0.28, -0.01, I-2 = 71%, p(for heterogeneity) < 0.00001) and a lower progressive motility (pooled SMD = -0.18; 95% CI: -0.29, -0.06; I-2 = 59%, p(for heterogeneity) < 0.0001). However, the significant differences disappeared, along with the large inter-study heterogeneity, when analyses were restricted to studies clearly reporting the inclusion of men without clinical evidence of seminal tract infection. Discussion and Conclusion Leukocytospermia in men seeking consultation for couple subfertility is not associated with a reduced fertility after ART and with altered semen quality in populations asymptomatic for genital tract infection. Therefore, the current clinical criteria for definition of leukocytospermia should be re-assessed in subfertile couples attending a fertility clinic