License to bind: Role of glycoproteins in male (in)fertility.

Science linking environmental contaminant exposures with fertility and reproductive health impacts in the adult male

Lessons learned in andrology: looking at the spermatozoa in context.

Do some addictions interfere with fertility?

With the increasing global incidence of infertility, the influence of environmental factors, lifestyle habits, and nutrients on reproductive health has gradually attracted the attention of researchers. The quantity and quality of sperm play vital roles in male fertility, and both characteristics can be affected by external and internal factors. In this review, the potential role of genetic, environmental, and endocrine factors; nutrients and trace elements in male reproductive health, spermatozoa function, and fertility potency and the underlying mechanisms are considered to provide a theoretical basis for clinical treatment of infertility.

BackgroundA number of different types of endocrine‐disrupting chemicals (EDCs) including bisphenol A, phthalates, pesticides, and other environmental chemicals have been shown to adversely impact upon male reproductive health. Understanding the potential effects of EDCs on male reproductive health may enable the development of novel treatments and early prevention of the effects of EDCs on male infertility and their potential long‐term sequelae. This review critically evaluates the research performed in this area and explores potential harmful effects of EDCs in animals and humans, including the possibility of trans‐generational transmission.MethodsA literature review was conducted using electronic databases using the following terms: ‘endocrine disrupt*’ OR ‘endocrine disruptors’ OR ‘endocrine disruptor chemicals’ OR ‘EDC’ AND ‘sperm*’ OR ‘spermatozoa’ OR ‘spermatozoon’ OR ‘male reproductive health’ OR’ male fertility’.Main findingsSeveral studies have shown that EDCs have a variety of pathophysiological effects. These include failure of spermatogenesis, embryonic development, the association with testicular cancer, and long‐term metabolic effects.ConclusionsSeveral studies observe correlations between chemical doses and at least one sperm parameter; however, such correlations are sometimes inconsistent between different studies. Mechanisms through which EDCs exert their pathophysiological effects have not yet been fully elucidated in human studies.

Phosphodiesterases (PDEs) are a family of enzymes that regulate intracellular levels of cyclic nucleotides, such as cyclic adenosine monophosphate and cyclic guanosine monophosphate. PDEs are considered key modulators of cellular signaling processes, including those governing male reproductive health. Owing to the pivotal role played by PDEs in male reproductive health, pharmacologic inhibition of PDEs has gained substantial attention in improving male reproductive health. However, despite the potential therapeutic application of PDE inhibitors (PDEis) in this field, a comprehensive understanding remains limited of the PDE subtype-specific actions in male reproductive tissues, the potential off-target effects, and the long-term safety of PDE inhibition, emphasizing a critical gap in current knowledge. A systematic evaluation of existing evidence on the role of PDEs, as well as the therapeutic application of PDEis and their safety, is necessary for a better understating in the context of male reproductive and sexual health. This narrative review aims to critically synthesize and highlight the current evidence on the function of PDEs in male reproductive organs and evaluate the clinical applications of PDEis as therapeutic agents in male reproductive health and sexual medicine. A comprehensive literature search was conducted in PubMed and Scopus to identify the expression and function of PDEs in male reproductive organs and the use of PDEis for the treatment of erectile dysfunction and reproductive cancer and for the improvement of male fertility. PDEs of different families are expressed in a tissue-specific manner in the testis, epididymis, prostate gland, seminal vesicle, and penis, indicating their significant role in male reproductive health. Inhibitors of PDEs, even though popularly known for their therapeutic role in treating erectile dysfunction, have exhibited a promising role in the treatment of prostate cancer, testicular cancer, testicular function enhancement, and sperm motility improvement. PDEis have a promising role in improving male reproductive and sexual health. However, the lack of studies addressing their long-term health effects and safety limits their routine therapeutic applications for improving male reproductive health. Future systematic clinical trials and mechanistic studies can certainly illuminate the possible role of PDEis in improving male reproductive health.

OPINION article Front. Endocrinol., 08 November 2013 | https://doi.org/10.3389/fendo.2013.00169

Male infertility as a window to health

GENERAL COMMENTARY article Front. Public Health, 22 June 2015Sec. Environmental health and Exposome Volume 3 - 2015 | https://doi.org/10.3389/fpubh.2015.00165

There is a global crisis in male reproductive health. Evidence comes from globally declining sperm counts and increasing male reproductive system abnormalities, such as cryptorchidism, germ cell tumors, and onset of puberty. Male factor infertility occurs in ~40% of couples experiencing infertility. Data demonstrate an association between male infertility and overall health. Associated significant health conditions include diabetes mellitus, metabolic disorders, and cardiovascular disease. Adding to the complexity is that men typically do not seek health care unless there is acute medical need or, as in the case of the infertile couple, the male goes for a reproductive examination and semen analysis. However, 25% of the time a reproductive health examination does not occur. Couples are increasingly utilizing IVF at more advanced ages, and advanced paternal age is associated with increased risk for (i) adverse perinatal outcomes for both offspring and mother; (ii) early child mortality, cancer, and mental health issues. In addition to age, paternal lifestyle factors, such as obesity and smoking, impact not only the male fertility but also the offspring wellness. The purpose of this paper was (i) to spotlight emerging and concerning data on male reproductive health, the relationship(s) between male reproductive and somatic health, and the heritable conditions father can pass to offspring, and (ii) to present a strategic roadmap with the goals of increasing (a) the awareness of men and society on the aforementioned, (b) the participation of men in healthcare seeking, and (c) advocacy to invigorate policy and funding agencies to support increased research into male reproductive biology. The Male Reproductive Health Initiative (MRHI) is a newly established and rapidly growing global consortium of key opinion leaders in research, medicine, funding and policy agencies, and patient support groups that are moving forward the significant task of accomplishing the goals of the strategic roadmap.

Sperm DNA Integrity From Sperm to Egg

The determination of reproductive safety in men during and after cancer treatment

The EAU guidelines on male sexual and reproductive health state that both partners of the infertile couple should undergo simultaneous investigation. To assess the prevalence and the characteristics of infertile men who were referred for an andrological evaluation after failed attempts of Assisted Reproductive Technology (ART) with those who were evaluated at the beginning of their infertility pathway at a single academic centre over a 17-year period. Data of 3213 primary infertile couples assessed between 2003 and 2020 were analysed. Descriptive statistics compared the overall characteristics of male partners of couples with (+ART) or without (-ART) previous ART prior to andrological consultation. Logistic regression models analysed variables associated with +ART. Local polynomial regression models explored the probability of +ART over the analysed time frame. Of all, 493 (15.3%) participants were +ART. Patients and female partners' age was higher in +ART couples (all p ≤ 0.04). Sperm concentration, progressive sperm motility and normal sperm morphology were lower in +ART than in -ART patients (all p<0.001), along with a greater percentage of non-obstructive azoospermia in +ART compared to -ART men (p<0.0001). At univariable analysis, patient age and partner age>35 years and a less recent assessment were associated with +ART status (all p ≤ 0.04). Male age and less recent years of assessment were also independent predictors of +ART, after accounting for partner's age>35 years (all p<0.01). A not significant decrease of this pattern was observed throughout the last 7 years at local polynomial regression models. Overall awareness towards the importance of a comprehensive evaluation for the male partner of every infertile couple should therefore be further strengthened. Approximately 15% of couples still undergo ART without any initial andrological evaluation in the real-life setting. A not significant decrease in this trend was observed over most recent years.

Male fertility is complex and influenced by genetic, hormonal, environmental and lifestyle factors. However, limitations to human studies necessitate the use of reliable preclinical models to better understand the underlying mechanisms of male fertility. Rhesus macaques (Macaca mulatta), with their close genetic and physiological similarities to humans, offer an invaluable model for male reproductive health studies. The suitability of rhesus macaques for studying male infertility is based on similarities in spermatogenesis, hormonal cycles and the way in which assisted reproductive technologies can be applied, and key differences and similarities between human and rhesus macaque sperm structure, function and cryopreservation techniques highlight the translational potential of findings derived from macaque models. Furthermore, insights into the epigenetic and proteomic characteristics of sperm in both species improve understanding of how these findings can help to advance clinical diagnostics, male contraception and fertility preservation and illuminate the regulatory omics of normal reproduction. Thus, the rhesus macaque model offers critical insights into male fertility and studies in this species could contribute to advances in therapies for male infertility.

Cancer risk and male Infertility: Unravelling predictive biomarkers and prognostic indicators