Semen quality and sperm DNA damage in relation to urinary bisphenol A among men from an infertility clinic.

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.

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

BackgroundEvidence on human semen quality as it relates to exposure to various metals, both essential (e.g., zinc, copper) and nonessential (e.g., cadmium, lead), is inconsistent. Most studies to d...

Cadmium, lead, and other metals in relation to semen quality: human evidence for molybdenum as a male reproductive toxicant.

Background Optimization of assisted conception outcomes involves the development of rapid, safe, effective techniques for the isolation of functional human spermatozoa free from significant DNA damage. In this study we describe a novel electrophoretic sperm isolation technique that achieves these objectives. Methods The separation system consisted of a cassette comprising two 400 mul chambers separated by a polycarbonate filter containing 5 micromol/l pores and bounded by a 15 kDa polyacrylamide membrane to allow the free circulation of buffer. Semen was introduced into one chamber, current applied (75 mA at variable voltage) and within seconds a purified suspension of spermatozoa could be collected from the adjacent chamber. These cells were assessed for their count, viability, motility, morphology and DNA integrity. Results The suspensions generated by the electrophoretic separation technique contained motile, viable, morphologically normal spermatozoa and exhibited low levels of DNA damage. Moreover, these cell suspensions were free from contaminating cells, including leukocytes. The technique was comparable to discontinuous gradient centrifugation except that it took a fraction of the time and generated cells with significantly less DNA damage. Conclusion Electrophoretic separation represents a highly effective, novel approach for the isolation of spermatozoa for assisted conception purposes.

Development of a novel electrophoretic system for the isolation of human spermatozoa.

Many studies have shown how a 'paternal effect' can cause repeated assisted reproduction failures. In particular, with increasing experience of intracytoplasmic sperm injection (ICSI), it became evident that spermatozoa from some patients repeatedly fail to form viable embryos, although they can fertilize the oocyte and trigger early preimplantation development. Many authors have shown how this paternal effect can be traced back to anomalies in sperm chromatin organization: the spermatozoa of subfertile men are characterized by numerical abnormalities in spermatozoal chromosome content, Y chromosome microdeletions, alterations in the epigenetic regulation of paternal genome and non-specific DNA strand breaks. In particular, pathologically increased sperm DNA fragmentation is one of the main paternal-derived causes of repeated assisted reproduction failures in the ICSI era. The intention of this review is to describe nuclear sperm DNA damage, with emphasis on its clinical significance and its relationship with male infertility. Assessment of sperm DNA damage appears to be a potential tool for evaluating semen samples prior to their use in assisted reproduction, helping to select spermatozoa with intact DNA or with the least amount of DNA damage for use in assisted conception.

https://www.rbmojournal.com/article/S1472-6483(10)60678-5/pdf

Clinical relevance of sperm DNA damage in assisted reproduction.

As little information exists on the semen variability in infertile men, this study aimed at analysing the within-subject variability of semen from men with infertile marriages included in an intrauterine insemination (IUI) programme. Five ejaculates from each of 436 men (2180 specimens) were analysed. The within-subject coefficients of variation (CV(w)) were high for all parameters (semen volume, sperm concentration, forward motility and combined parameters), ranging from 0.73 for the total motile sperm count to 0.27 for the semen volume. Nevertheless, within-subject fluctuations were smaller than the between-subject variability, as indicated by high Intraclass Correlation Coefficient (ICC) values, which, however, significantly lowered when <or=3 samples were analysed against five samples. Neither seasonality nor the length of abstinence between 3 and 7 days significantly affected within-subject semen variability, whereas total motile sperm count was significantly and negatively affected at 2 days of abstinence. In 253 cycles of double IUI, performed in two consecutive days, semen volume and parameters including volume decreased in the second sample, but semen quality improved in most cases of oligo- and/or asthenozoospermia. Useful information for clinical purposes is provided.

Within-subject variation of seminal parameters in men with infertile marriages.

gp20, a sialylglycoprotein of human sperm homologous to CD52, is present everywhere on the surface of the freshly ejaculated sperm but is prevalently localized in the equatorial region of the head of capacitated sperm. In the present study, we confirmed this feature on large scale and correlated equatorial exposure of the antigen to the presence of serum albumin (SA) in the capacitation medium. Furthermore, we analyzed the relationship between the presence of the antigen and its equatorial exposure after capacitation and fertility, by comparing immunostaining for gp20 in the motile fraction of spermatozoa from fertile and subfertile men. A significantly higher percentage of nonimmunostained spermatozoa before capacitation (38.5% +/- 23 vs. 12% +/- 7, P < 0.0001) and a lower increase in the percentage of sperm with equatorial localization after capacitation (19.3% +/- 25 vs. 34.6% +/- 22, P = 0.039) were observed in subfertile men (n = 60) compared to fertile men (n = 15). In the whole study group, a positive correlation was also found between the percentage of spermatozoa exhibiting equatorial localization in capacitated samples and normal head forms (R = 0.50; P < 0.0001).

Expression of gp20, a human sperm antigen of epididymal origin, is reduced in spermatozoa from subfertile men

The demonstration of a stimulatory effect of progesterone (P) on the sperm/oocyte fusion has provided the most relevant biological evidence of the effect of P on sperm functions involved in fertilization. Some evidence exists that 17alpha-hydroxyprogesterone (17alphaOH-P) and 17beta-oestradiol (17beta-E2), could also exert non-genomic effects on human spermatozoa and a role for 17beta-E2 as a possible physiological modulator of P action on spermatozoa has been suggested. This study aimed to determine the effect of the exposure of human spermatozoa to 17alphaOH-P and 17beta-E2 on sperm/oocyte fusion as well as the possible interference of 17beta-E2 with the effect of P. The effect of steroids on sperm/oocyte fusion was assessed by means of the hamster egg penetration test (HEPT). The exposure of capacitated sperm suspensions to scalar doses of 17alphaOH-P produced a significant enhancement of penetrations/oocytes with a dose/response effect. It was equal to 75.3% of that produced by equimolar doses of P. Conversely, 17beta-E2 (from 100 nM to 50 microM) did not produce any significant effect when added either before or after capacitation. Moreover, the sperm pre-incubation with 17beta-E2 did not interfere with the stimulatory effect of P. These results support a physiological role for 17OH-P in the process of fertilization, but not a role for 17beta-E2 as a possible physiological modulator of P action on spermatozoa.

Evaluation of the effect of 17αOH‐progesterone and 17β‐oestradiol on human sperm ability to fuse with oocytes: comparison and possible interference with the effect of progesterone

In this study, the effect of human sperm exposure to progesterone on sperm/oocyte fusion, using the hamster egg penetration test, and on sperm/zona pellucida (ZP) binding, using the hemizona assay, was investigated under various experimental conditions. A brief exposure of human spermatozoa to progesterone exerted a stimulatory effect on sperm/oocyte fusion which was dose-dependent, capacitation-dependent, influenced by the source of serum albumin in capacitating medium, and was higher than that produced by the exposure to progesterone from the onset of capacitation. The exposure of capacitated spermatozoa to progesterone during 20 min-spermatozoa/ZP-coincubation produced an enhancement of ZP-binding, which was not significantly influenced by the source of serum albumin in capacitating medium. A significantly lower ZP-binding was exhibited by spermatozoa exposed to progesterone from the beginning of capacitation. These results indicate that progesterone exerts a stimulatory effect on human sperm's fertilizing ability, which occurs mainly in post-capacitation events directly involved in sperm/oocyte fusion and in ZP-binding. Conditions optimizing these effects are provided. They should be taken into account in the standardization of experimental and clinical studies designed to evaluate the response of human spermatozoa to progesterone.

https://onlinelibrary.wiley.com/doi/pdf/10.1046/j.1365-2605.2002.00333.x

Effect of human sperm exposure to progesterone on sperm-oocyte fusion and sperm-zona pellucida binding under various experimental conditions.

Some evidence suggests that the non-genomic effects exerted by progesterone (P) on human spermatozoa are mediated by membrane receptor(s) displaying the C-terminal domain, but not the N-terminal domain of the genomic P receptor (PR). This study aimed at determining whether the monoclonal antibody (mAb) c-262, directed against the C-terminal domain of the genomic PR, counteracts the stimulatory effect of P on the human sperm ability to fuse with oocytes. Sperm/oocyte fusion was evaluated by means of the hamster egg penetration test. The brief exposure of capacitated spermatozoa to P produced a stimulatory effect on sperm/oocyte fusion. mAb c262 counteracted this stimulatory effect in a dose-dependent manner. No counteraction was observed when capacitated spermatozoa were pre-exposed to PGR-312, a mAb directed against the N-terminal domain of the genomic PR. These results reinforce the hypothesis that the non-genomic effects exerted by P on human spermatozoa are mediated by membrane receptor(s) displaying the C-terminal domain, but not the N-terminal domain of the genomic PR.

B. Macerola

Papers

Within-subject variation of seminal parameters in men with infertile marriages.

Expression of gp20, a human sperm antigen of epididymal origin, is reduced in spermatozoa from subfertile men

Evaluation of the effect of 17αOH‐progesterone and 17β‐oestradiol on human sperm ability to fuse with oocytes: comparison and possible interference with the effect of progesterone

Effect of human sperm exposure to progesterone on sperm-oocyte fusion and sperm-zona pellucida binding under various experimental conditions.

Monoclonal antibody c262 counteracts the stimulatory effect of progesterone on sperm-oocyte fusion.