Background
The recent emergence of COVID-19 poses a global health emergency. One of the most frequently reported data is sex-related severity and mortality: according to the last available analysis ...on 239,709 patients in Italy, lethality is 17.7% in men and 10.8% in women, with 59% of total deaths being men. Interestingly, the infection rate is lower in males than in females, with 45.8% and 54.2% of positive cases, respectively, suggesting that gender-related factor may worsen disease evolution. A tentative hypothesis to explain these findings is the role of angiotensin-converting enzyme 2 (ACE2) and serine protease TMPRSS2 involved in viral infection.
Purpose
In this review, we summarize the available evidence pointing to gender-related differences in ACE2 and TMPRSS2 expression, from both genetic and endocrine points of view.
Results
Altogether, available evidence points toward two not-mutually exclusive mechanisms in gender susceptibility to COVID-19 by sex hormonal regulation of ACE2 and TMPRSS2. On one hand, ACE2 expression could be increased in women, either by estrogens or constitutively by X chromosome inactivation escape or by reduced methylation, providing a larger reservoir of ACE2 to maintain the fundamental equilibrium of RAS regulatory axis. On the other, low levels of androgens in women may keep at low levels TMPRSS2 expression, representing a further protective factor for the development of COVID-19 infection, despite the increased expression of ACE2, which represents the Trojan horse for SARS-CoV-2 entry.
Conclusions
Both mechanisms consistently point to the role of sex hormones and sex chromosomes in the differential severity and lethality of COVID-19 in men and women.
Perfluoroalkyl compounds (PFCs) are a class of organic molecules used in industry and consumer products. PFCs are non-biodegradable and bioaccumulate in the environment and for these reasons they ...have been a major subject of research regarding their toxicity, environmental fate, and sources of human exposure, since they have been shown to induce severe health consequences, such as neonatal mortality, neurotoxicity and immunotoxicity. The aim of this review is to explore the existing knowledge of the interplay between PFCs exposure and human health, with a focus on male reproductive health, given the emerging gender differences in PFCs clearance and their interaction with sex hormones receptors. A comprehensive PUBMED search was performed using relevant key terms for PFCs and male fertility. Different degrees of evidence suggest an impairment of semen parameters and sex hormones in relation to PFCs exposure. These preliminary results point towards a sex-dependent pharmacodynamics and clearance, with males having a much higher tendency to accumulation. Moreover, because of the widespread environmental occurrence of these chemicals, along with their ability to cross the placental barrier, exposure of the foetus to these compounds is inevitable. This is of concern because foetal development of the male reproductive organs may be disturbed by exposure to exogenous factors. These findings clearly suggest an antiandrogenic potential of PFCs and a link between endocrine disruptors and disorders of male health.
Purpose
Infertility affects 15–20% of couples and male factors are present in about half of the cases. For many aspects related to the diagnostic and therapeutic approach of male factor infertility, ...there is no general consensus, and the clinical approach is not uniform.
Methods
In the present document by the Italian Society of Andrology and Sexual Medicine (SIAMS), endorsed by the Italian Society of Embryology, Reproduction, and Research (SIERR), we propose evidence-based recommendations for the diagnosis, treatment, and management of male factor infertility to improve patient and couple care.
Results
Components of the initial evaluation should include at minimum medical history, physical examination, and semen analysis. Semen microbiological examination, endocrine assessment, and imaging are suggested in most men and recommended when specific risk factors for infertility exist or first-step analyses showed abnormalities. Full examination including genetic tests, testicular cytology/histology, or additional tests on sperm is clinically oriented and based on the results of previous investigations. For treatment purposes, the identification of the specific cause and the pathogenetic mechanism is advisable. At least, distinguishing pre-testicular, testicular, and post-testicular forms is essential. Treatment should be couple-oriented, including lifestyle modifications, etiologic therapies, empirical treatments, and ART on the basis of best evidence and with a gradual approach.
Conclusion
These Guidelines are based on two principal aspects: they are couple-oriented and place high value in assessing, preventing, and treating risk factors for infertility. These Guidelines also highlighted that male infertility and in particular testicular function might be a mirror of general health of a man.
Abstract
STUDY QUESTION
Could sperm telomere length (STL) represent a novel parameter and biomarker of sperm quality?
SUMMARY ANSWER
STL is associated with standard semen quality parameters and, more ...importantly, it is significantly associated with levels of DNA fragmentation and sperm protamination.
WHAT IS KNOWN ALREADY
Telomeres are fundamental for genome integrity. Recent studies have demonstrated that STL increases with age and men with oligozoospermia have shorter sperm telomeres than normozoospermic men.
STUDY DESIGN, SIZE, DURATION
Cohort study conducted from September 2014 to June 2015 on 100 subjects with normal standard semen parameters.
PARTICIPANTS/MATERIALS, SETTING, METHODS
STL was measured indirectly by quantitative polymerase chain reaction using telomere/single-copy gene ratio, sperm DNA fragmentation by terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling assay and protamination by aniline blue staining. Data were analyzed for determining the relationships between STL, standard semen parameters and DNA fragmentation and protamination.
MAIN RESULTS AND THE ROLE OF CHANCE
Among standard semen parameters, STL was positively associated with progressive motility (P = 0.004) and vitality (P = 0.007). STL was significantly and negatively associated with sperm DNA fragmentation (P = 0.001) and significantly and positively associated with protamination (P = 0.002). The role of chance was limited and the findings have biological relevance and a pathophysiological explanation.
LIMITATIONS, REASONS FOR CAUTION
For the present study, we deliberately selected only men with normozoospermia to better analyze whether STL might represent a biomarker of sperm quality beyond traditional sperm parameters. Additional studies in proven fertile men with normal sperm parameters are needed.
WIDER IMPLICATIONS OF THE FINDINGS
The measurement of STL is a simple and rapid method that offers further information about the quality of sperm. The results of this study demonstrate that STL could be considered as an additional sperm parameter and opens new perspectives in the evaluation of the infertile male. Additional studies will clarify the significance of this parameter also as a prognostic biomarker in assisted reproduction.
STUDY FUNDING/COMPETING INTEREST(S)
No external funding was either sought or obtained for this study. There are no conflicts of interest to be declared.
Female fecundity is finely regulated by hormonal signaling, representing a potential target for endocrine-disrupting chemicals. Among the chemicals of most concern are the perfluoroalkyl substances ...(PFAS), widely used in consumer goods, that are associated with adverse effects on reproductive health. In this context, the endometrium clearly represents an important fertility determining factor. The aim of this study was to investigate PFAS interference on hormonal endometrial regulation. This study was performed within a screening protocol to evaluate reproductive health in high schools. We studied a cohort of 146 exposed females aged 18–21 from the Veneto region in Italy, one of the four areas worldwide heavily polluted with PFAS, and 1080 non-exposed controls. In experiments on Ishikawa cells included UV–Vis spectroscopy, microarray analysis and qPCR. We report a significant dysregulation of the genetic cascade leading to embryo implantation and endometrial receptivity. The most differentially-expressed genes upon PFOA coincubation were ITGB8, KLF5, WNT11, SULT1E1, ALPPL2 and G0S2 (all p < 0.01). By qPCR, we confirmed an antagonistic effect of PFOA on all these genes, which was reversed at higher progesterone levels. Molecular interference of PFOA on progesterone was confirmed by an increase in the intensity of absorption spectra at 250 nm in a dose-dependent manner, but not in the presence of β-estradiol. Age at menarche (+164 days, p = 0.006) and the frequency of girls with irregular periods (29.5% vs 21.5%, p = 0.022) were significantly higher in the exposed group. Our results are indicative of endocrine-disrupting activity of PFAS on progesterone-mediated endometrial function.
•PFAS could reduce female fecundity by interfering with hormonal pathways.•PFOA shows consistent binding affinity for progesterone.•Progesterone-activated genes in endometrial cells are dysregulated by PFOA.•Age at menarche and irregular periods were higher in exposed young women.
Background
Infertility, which is defined as the inability to conceive after at least 12 months of regular unprotected sexual intercourses, affects about 15–20% of couples worldwide and a male factor ...is involved in about half of the cases. The development of assisted reproductive technology (ART) made it possible to conceive also to individuals affected from severe oligospermia or azoospermia. However, the impact of the male factor on embryo development, implantation, prevalence of chromosomal abnormalities, genetic and epigenetic alterations, and clinical and obstetric outcomes is still controversial.
Purpose
This narrative review examines the indications, minimum access criteria, and outcomes by individual ART technique in relation to the male factor.
Purpose
The recent pandemic of severe acute respiratory syndrome (SARS) due to coronavirus (CoV) 2 (SARS-CoV-2) has raised several concerns in reproductive medicine. The aim of this review is to ...summarize available evidence providing an official position statement of the Italian Society of Andrology and Sexual Medicine (SIAMS)
Methods
A comprehensive Pubmed, Web of Science, Embase, Medline and Cochrane library search was performed. Due to the limited evidence and the lack of studies, it was not possible to formulate recommendations according to the Oxford 2011 Levels of Evidence criteria.
Results
Several molecular characteristics of the SARS-CoV-2 can justify the presence of virus within the testis and possible alterations of spermatogenesis and endocrine function. Orchitis has been reported as a possible complication of SARS-CoV infection, but similar findings have not been reported for SARS-CoV-2. Alternatively, the orchitis could be the result of a vasculitis as COVID-19 has been associated with abnormalities in coagulation and the segmental vascularization of the testis could account for an orchitis-like syndrome. Finally, available data do not support the presence of SARS-CoV-2 in plasma seminal fluid of infected subjects.
Conclusion
Data derived from other SARS-CoV infections suggest that in patients recovered from COVID-19, especially for those in reproductive age, andrological consultation and evaluation of gonadal function including semen analysis should be suggested. Studies in larger cohorts of currently infected subjects are warranted to confirm (or exclude) the presence of risks for male gametes that are destined either for cryopreservation in liquid nitrogen or for assisted reproduction techniques.
Cannabinoids and endocannabinoids negatively influence sperm functions. These substances have been demonstrated in many mammalian tissues, including male and female reproductive tracts, and previous ...studies have shown the presence of functional receptors for cannabinoids in human sperm. The present study, by means of RT-PCR and Western blot techniques, demonstrates that human sperm express the CB1, but not CB2, cannabinoid receptor (CB-R) subtype located in the head and middle piece of the sperm. The activation of this receptor by anandamide reduces sperm motility and inhibits capacitation-induced acrosome reaction. Activation of the CB1-R did not induce any variation in sperm intracellular calcium concentrations, but produced a rapid plasma membrane hyperpolarization that was reduced by the K+ channel blocker tetraethylammonium. The effects of anandamide on human sperm motility were dependent on the reduction of sperm mitochondrial activity as determined by rhodamine 123 fluorescence. The specificity of anandamide effects in human sperm were confirmed by the effects of the CB1-R antagonist SR141716. These findings provide additional evidence that human sperm express functional CB1-R, the activation of which negatively influences important sperm functions, and suggest a possible role for the cannabinoid system in the pathogenesis of some forms of male infertility.
C
ontext
Perfluoroalkyl-substances (PFAS) are chemical additives considered harmful for humans. We recently showed that accumulation of perfluoro-octanoic acid (PFOA) in human semen of exposed ...subjects was associated with altered motility parameters of sperm cells, suggesting direct toxicity.
Objectives
To determine whether direct exposure of human spermatozoa to PFOA was associated to impairment of cell function.
Patients and methods
Spermatozoa isolated from semen samples of ten normozoospermic healthy donors were exposed up to 2 h to PFOA, at concentrations from 0.1 to 10 ng/mL. Viability and motility parameters were evaluated by Sperm Class Analyser. Cell respiratory function was assessed by both mitochondrial probe JC-1 and respiratory control ratio (RCR) determination. Sperm accumulation of PFOA was quantified by liquid chromatography–mass spectrometry. Expression of organic ion-transporters OATP1 and SLCO1B2 was assessed by immunofluorescence and respective role in PFOA accumulation was evaluated by either blockade with probenecid or membrane scavenging through β-cyclodextrin (β-CD). Plasma membrane fluidity and electrochemical potential (ΔΨp) were evaluated, respectively, with Merocyanine-540 and Di-3-ANEPPDHQ fluorescent probes.
Results
Compared to untreated controls, a threefold increase of the percentage of non-motile sperms was observed after 2 h of exposure to PFOA regardless of the concentration of PFOA, whilst RCR was significantly reduced. Only scavenging with β-CD was effective in reducing PFOA accumulation, suggesting membrane involvement. Altered membrane fluidity, reduced ΔΨp and sperm motility loss associated with exposure to PFOA were reverted by β-CD treatment.
Conclusion
PFOA alters human sperm motility through plasma-membrane disruption, an effect recovered by incubation with β-CD.
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