On sperm nuclear zinc and chromatin decondensation : an in vitro study on the physiology of the ejaculated human spermatozoon

Ejaculated human spermatozoa were studied in vitro with respect to their capacity to decondense the chromatin in sodium dodecyl sulfate (SDS). The content of zinc in sperm heads was studied in epididymal, vasal, and ejaculated human spermatozoa. These were the main results: (1) Soon after ejaculation most spermatozoa decondensed the chromatin in SDS with zinc-chelating EDTA. Only few spermatozoa decondensed in SDS alone. (2) During storage, many spermatozoa lost the capacity to decondense in SDS-EDTA. Half of all spermatozoa lost this capacity within the first hour after ejaculation whether they were washed and stored in a buffered salt solution (BSS) within 20 minutes after ejaculation, or simply stored in the original seminal plasma. During prolonged storage (24 hours) the capacity was better retained among spermatozoa stored in BSS, than in those stored in seminal plasma. Furthermore, among spermatozoa treated with EDTA before storage, the loss of capacity for decondensation during storage was enhanced. In contrast, the initial capacity for decondensation was completely prevented in spermatozoa supplemented with zinc during 24 h storage in BSS. (3) The ejaculated human sperm head contained significant amounts of zinc bound within the nuclear matrix. With EDTA-treatment, 90% of sperm head zinc could be removed soon after ejaculation. After 24 h storage in seminal plasma significantly less zinc could be released by exposure to EDTA. (4) Epididymal and vasal sperm heads had significantly lower contents of zinc than ejaculated sperm heads. (5) The zinc content of ejaculated sperm heads from various portions of split­ ejaculates was neither correlated to the total seminal plasma zinc concentration, nor to the concentrations of measured subfractions of zinc bound to various groups of zinc-ligands. However, most of the variations in sperm head zinc could be explained by variations in total sperm number and concentration of fructose secreted by the seminal vesicles. The results seem to justify the conclusion that the human spermatozoon takes up zinc at ejaculation from the concomitantly expelled prostatic fluid, and that zinc subsequently acts as a reversible stabilizer of the sperm chromatin. The results also imply that inappropriate stabilization by zinc of the sperm chromatin is likely to occur in spermatozoa from men with prostatic dysfunction, men expelling the spermatozoa mainly in vesicular fluid, and men expelling high total numbers of spermatozoa. The possibility is discussed that zinc stabilizes the quarternary structure of the sperm chromatin by chelating between e.g. amino- and thiol-groups of adjacent nucleoprotein fibers. Concomitantly, zinc would protect these thiol-groups from being comitted into superstabilizing disulfide-bridge crosslinks. Thereby would zinc preserve a potential of the chromatin for rapid decondensation in the ooplasm

Sperm Nuclear Zinc, Chromatin Stability, and Male Fertility

Zinc excreted from the human prostate secures a high content of zinc in the sperm nucleus and contributes to the stability of the quaternary structure of the chromatin. After ejaculation, in vitro, a second type of stability, most probably involving disulfide- bridge crosslinks, supersedes the zinc-dependent stability. Normally, the nucleus of the ejaculated spermatozoon remains stable, i.e., it does not decondense when exposed to a detergent (e.g., sodium dodecyl sulfate -SDS), whereas a spermatozoon which has been exposed to a zinc- chelating medium becomes destabilized and decondenses in SDS. Spontaneous decondensation in SDS, i.e., without prior treatment with zinc-chelators, occurs among many spermatozoa from some infertile men, especially men with impaired secretory function of the prostate. This indicates that spontaneously decondensing spermatozoa have an inadequate content of zinc at ejaculation. Here, zinc in the sperm nucleus and chromatin stability was studied in semen samples from a group of men living in marriages with hitherto unexplained cause for infertility, and a group of fertile donors, who participated in an insemination program. Sperm nuclear zinc was studied with X-ray microanalysis and chromatin stability was assessed as percentage spermatozoa with stable sperm heads after exposure to SDS. Fertile donors had higher content of zinc in the sperm nuclei and had also higher proportions spermatozoa with a stabilized chromatin, than had the men living in infertile marriages. A positive rank- correlation was found between percentage of stable spermatozoa and sperm nuclear zinc. Zinc may stabilize the chromatin by forming salt-bridges between thiol-and amino- residues of adjacent nucleoprotamine-fibers

Male reproductive health statement:(XIIIth international symposium on Spermatology, May 9th--12th 2018, Stockholm, Sweden

International audienc

Distribution of Semen Examination Results 2020 - a follow up of data collated for the WHO semen analysis manual 2010

Background: It is now 11 years since publication of the WHO 2010 guidelines for semen assessment values, and it is critical to determine whether they are still valid and/or whether they should be modified.Objectives: To utilise data published since 2010 and combine these with data used in the 2010 assessment to provide an updated and more comprehensive representation of the fertile man. This may be utilised to present an updated distribution of values for use by WHO in 2021.Materials and Methods: Two specific analyses were performed namely, (1) Analysis 1: Examination of published data following publication of WHO 2010 [termed 2010–2020 data]. (2) Analysis 2: Examination of the data used to help formulate the 2010 distribution of values combined with the data from Analysis (1) [termed WHO 2020].Results: In total, data from more than 3500 subjects, from twelve countries and five continents were analysed. The 5 th centile values for concentration, motility and morphology are: 16 × 10 6/ml, 30% progressive motility [42% total motility] and 4% normal forms.Discussion: This study presents substantial additional information to establish more comprehensive and globally applicable lower reference values for semen parameters for fertile men although they do not represent distinct limits between fertile and subfertile men. There are still data missing from many countries and, some geographical regions are not represented. Moreover, the number of subjects although significant is still relatively low (&lt;4000).Conclusion: These distributions of values now include semen analysis providing a more global representation of the fertile man. Increasing the number of subjects provides robust information that is also more geographically representative. </p

The diagnosis of male infertility:an analysis of the evidence to support the developments of global WHO guidance. Challenges and future research opportunities

Background: Herein, we describe the consensus guideline methodology, summarize the evidence-based recommendations we provided to the World Health Organization (WHO) for their consideration in the development of global guidance and present a narrative review of the diagnosis of male infertility as related to the eight prioritized (problem or population (P), intervention (I), comparison (C) and outcome(s) (O) (PICO)) questions. Additionally, we discuss the challenges and research gaps identified during the synthesis of this evidence.Objective and Rationale: The aim of this paper is to present an evidence-based approach for the diagnosis of male infertility as related to the eight prioritized PICO questions.Search Methods: Collating the evidence to support providing recommendations involved a collaborative process as developed by WHO, namely: identification of priority questions and critical outcomes; retrieval of up-to-date evidence and existing guidelines; assessment and synthesis of the evidence; and the formulation of draft recommendations to be used for reaching consensus with a wide range of global stakeholders. For each draft recommendation the quality of the supporting evidence was then graded and assessed for consideration during a WHO consensus.Outcomes: Evidence was synthesized and recommendations were drafted to address the diagnosis of male infertility specifically encompassing the following: What is the prevalence of male infertility and what proportion of infertility is attributable to the male? Is it necessary for all infertile men to undergo a thorough evaluation? What is the clinical (ART/non ART) value of traditional semen parameters? What key male lifestyle factors impact on fertility (focusing on obesity, heat and tobacco smoking)? Do supplementary oral antioxidants or herbal therapies significantly influence fertility outcomes for infertile men? What are the evidence-based criteria for genetic screening of infertile men? How does a history of neoplasia and related treatments in the male impact on (his and his partner’s) reproductive health and fertility options? And lastly, what is the impact of varicocele on male fertility and does correction of varicocele improve semen parameters and/or fertility?Wider Implications: This evidence synthesis analysis has been conducted in a manner to be considered for global applicability for the diagnosis of male infertility

Evolution of the WHO “Semen” processing manual from the first (1980) to the sixth edition (2021)

As stated clearly in all editions of the WHO Laboratory Manual for the Examination and Processing of Human Semen, the goal of the manual is to meet the growing needs for the standardization of semen analysis procedures. With constant advances in andrology and reproductive medicine and the advent of sophisticated assisted reproductive technologies for the treatment of infertility, the manual has been continuously updated to meet the need for new, evidence-based, validated tests to not only measure semen and sperm variables but also to provide a functional assessment of spermatozoa. The sixth edition of the WHO manual, launched in 2021, can be freely downloaded from the WHO website, with the hope of gaining wide acceptance and utilization as the essential source of the latest, evidence-based information for laboratory procedures required for the assessment of male reproductive function and health

The diagnosis of male infertility: an analysis of the evidence to support the development of global WHO guidance-challenges and future research opportunities

Background: Herein, we describe the consensus guideline methodology, summarize the evidence-based recommendations we provided to the World Health Organization (WHO) for their consideration in the development of global guidance and present a narrative review of the diagnosis of male infertility as related to the eight prioritized (problem or population (P), intervention (I), comparison (C) and outcome(s) (O) (PICO)) questions. Additionally, we discuss the challenges and research gaps identified during the synthesis of this evidence. Objective and rationale: The aim of this paper is to present an evidence-based approach for the diagnosis of male infertility as related to the eight prioritized PICO questions. Search methods: Collating the evidence to support providing recommendations involved a collaborative process as developed by WHO, namely: identification of priority questions and critical outcomes; retrieval of up-to-date evidence and existing guidelines; assessment and synthesis of the evidence; and the formulation of draft recommendations to be used for reaching consensus with a wide range of global stakeholders. For each draft recommendation the quality of the supporting evidence was then graded and assessed for consideration during a WHO consensus. Outcomes: Evidence was synthesized and recommendations were drafted to address the diagnosis of male infertility specifically encompassing the following: What is the prevalence of male infertility and what proportion of infertility is attributable to the male? Is it necessary for all infertile men to undergo a thorough evaluation? What is the clinical (ART/non ART) value of traditional semen parameters? What key male lifestyle factors impact on fertility (focusing on obesity, heat and tobacco smoking)? Do supplementary oral antioxidants or herbal therapies significantly influence fertility outcomes for infertile men? What are the evidence-based criteria for genetic screening of infertile men? How does a history of neoplasia and related treatments in the male impact on (his and his partner's) reproductive health and fertility options? And lastly, what is the impact of varicocele on male fertility and does correction of varicocele improve semen parameters and/or fertility? Wider implications: This evidence synthesis analysis has been conducted in a manner to be considered for global applicability for the diagnosis of male infertility