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(A) Structure of dopachrome methyl ester, a chromogenic substrate used in enzymatic assays of MIF, and its tautomerized colorless product. (B) Relationship between seminal fluid MIF concentrations and the dopachrome decolorizing rate (tautomerase activity) (n = 18, r 2 = 0.88); Seminal fluid exhibited dopachrome tautomerase activity. (C) MIF tautomerase activity in seminal fluids obtained from normozoospermic subjects (controls, n = 27) and patients with abnormal sperm parameters (n = 68, P < 0.001).
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Macrophage migration inhibitory factor (MIF) is a ubiquitous cytokine that functions in reproduction and plays an important role in sperm maturation and motility. Here we reveal a correlation between MIF levels in human seminal fluid and fertility status. We identify an abnormal biphasic profile of MIF in the seminal fluid of patients with impaired...
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Citations
... a possible role for MIF in sperm motility and the observed negative relationship with seminal plasma zinc concentration 115,177 (Fig. 3). Furthermore, the observed amount of sperm-associated MIF has a negative correlation with sperm motility and sperm DNA fragmentation index (DFI) 178,179 . Thus, MIF has a role in sperm development and maturation, and might inhibit sperm motility during epididymal migration and storage (Table 1). ...
Sperm are transcriptionally and translationally quiescent and, therefore, rely on the seminal plasma microenvironment for function, survival and fertilization of the oocyte in the oviduct. The male reproductive system influences sperm function via the binding and fusion of secreted epididymal (epididymosomes) and prostatic (prostasomes) small extracellular vesicles (S-EVs) that facilitate the transfer of proteins, lipids and nucleic acids to sperm. Seminal plasma S-EVs have important roles in sperm maturation, immune and oxidative stress protection, capacitation, fertilization and endometrial implantation and receptivity. Supplementing asthenozoospermic samples with normospermic-derived S-EVs can improve sperm motility and S-EV microRNAs can be used to predict non-obstructive azoospermia. Thus, S-EV influence on sperm physiology might have both therapeutic and diagnostic potential; however, the isolation of pure populations of S-EVs from bodily fluids with current conventional methods presents a substantial hurdle. Many conventional techniques lack accuracy, effectiveness, and practicality; yet microfluidic technology has the potential to simplify and improve S-EV isolation and detection.
... Thus, the alteration of the thiol redox state is related to improper chromatin packing and subsequent DNA damage [24]. The macrophage migration inhibitory factor protein is physiologically involved in maintaining the redox state of thiol and abnormal levels have been found in the SP of patients with altered sperm parameters [25]. The absence of this protein has been shown in patients with a high ROS production [26]. ...
... Thelibrary search resulted in the identification of 137 records. Among these, 43 were duplicates and 25 were not pertinent to the aim of this systematic review. Fifty-two papers were excluded because of the study design, the patients enrolled, or the study outcome. ...
The prevalence of idiopathic male infertility is high, up to 75% of patients with abnormal sperm parameters. Hence, the research of its causes is mandatory. Oxidative stress (OS) can be responsible for male infertility in 30–80% of cases. In recent years, seminal plasma (SP) proteomics has developed as a useful tool to provide biomarkers of specific diseases. This systematic review aims to collect the available evidence on the changes of SP proteome in patients exposed to OS to provide possible SP biomarkers of sperm OS. To accomplish this, the following keyterms “seminal fluid proteome”, “seminal plasma proteome”, “oxidative stress”, and “sperm oxidative stress” were used and 137 records were found. Among these, 17 were finally included. Nine proteins involved with OS were found overexpressed in patients with OS. Twenty-three proteins were found differentially expressed in patients with clinical conditions associated with OS, such as varicocele, male accessory gland infection/inflammation, cigarette smoke, and obesity. These proteins do not seem to overlap among the clinical conditions taken into account. We speculate that specific SP proteins may mediate OS in different clinical conditions. Altogether, these results suggest that proteomics could help to better understand some of the molecular mechanisms involved in the pathogenesis of infertility. However, further studies are needed to identify potential biomarkers of male infertility with valuable clinical significance.
... MIF is a well-known pro-inflammatory mediator with important functions in human reproduction and prostatic physiology. As a T-cell cytokine, MIF is present in large quantities in human semen and it is transferred to spermatozoa during the epididymal transit, which has been correlated with sperm maturation and stability (176)(177)(178). A higher level of MIF is found in epididymis and associated with spermatozoa, prostasomes as well as the soluble fraction (179). ...
Currently, there are few male contraceptive methods that are purely based on prevention of the entry of the sperm into the female reproductive tract. An alternative approach for designing reversible male contraceptive is achieved by transient testicular heating (TTH). This treatment, through massive germ cell apoptosis, causes reversible oligospermia or azoospermia. Here, we describe as how TTH causes DNA damage, oxidative stress, apoptosis, autophagy, sperm protein expression, and alters the biochemical components of seminal plasma. Further understanding of TTH will help design safe and reversible male contraception.
... Three proteins are associated with motility sperm. L-dopachrome tautomerase is produced in the epididymis and transferred to sperm during epididymal transit, in addition to present a negative correlation with the percentage of motile human sperm (Frenette et al. 2005;Aljabari et al. 2007). Angiotensin-converting enzyme is also present in sperm membrane from ejaculated and equine epididymal spermatozoa (Ball et al. 2003), and this protein is associated with sperm motility (Costa and Thundathil 2012). ...
The Saanen is a highly productive breed, and for this reason, it has been raised in Brazil, but mostly under climate conditions completely different from where the breed originated. The objective of this study was to investigate variations in semen parameters and sperm membrane proteins from Saanen bucks (n = 7) raised in Northeastern Brazil, during dry season (September, October, and November) and rainy season (March, April, and May). We showed that during the dry season, sperm motility, concentration, and the percentage of normal sperm decreased as compared to the rainy season. Rectal temperatures of bucks had no significant (p > 0.05) variations during the dry and rainy seasons. However, temperatures of left and right skin testis were higher (p < 0.05) during the dry as compared to the rainy season. Expression of three proteins (lysine-specific demethylase 5D, adenosine triphosphate (ATP) synthase subunit d, and radial spoke head protein 9 homolog) in sperm membrane were more intense in rainy season and only one protein (cytosol aminopeptidase) had greater expression in the dry season of the year. Our results show that mechanisms of testicular thermoregulation of Saanen bucks did not prevent a decrease in seminal parameters during the dry season. This deterioration may be related to reduced expression of proteins associated with important functions in sperm membrane.
... Since its rediscovery as a proinflammatory cytokine, macrophage migration inhibitory factor (MIF) has demonstrated a widespread distribution and depending on its location, to play different roles (Frenette et al., 2005). Recent studies have indicated a broader scope for MIF activities including a role in reproduction, as it affects the sperm maturation and spermatozoa motility (Aljabari et al., 2007). In the male reproductive tract, MIF has been found in both the testes and the epididymis. ...
... The group of high MIF values included all the infertile individuals with either azoospermia or severe oligozoospermia, whereas all the other infertile individuals reported a low MIF concentration well below the MIF level of normal individuals. MIF levels, either higher or lower than that of normozoospermics is indicative of impaired fertilizing ability, which corresponds with the finding that a MIF threshold concentration is required for sperm maturation and movement (Aljabari et al., 2007). ...
Recent clinical and epidemiological studies worldwide suggest an increasing incidence of male factor infertility (MFI). Paucity of information on the biochemical analysis of seminal fluid in Sri Lanka prompted undertaking a pilot study to establish a clinical marker for the male fertility status in Sri Lanka based on the level of the cytokine, macrophage migration inhibitory factor (MIF) in seminal fluid, an area hitherto unexplored locally. The analysis was carried out on the semen samples of infertile males (N = 61) where age matched individuals (N = 30) with proven past paternity served as controls. D-dopachrome tautomerase assay was performed to assess the MIF level in semen while other seminal fluid parameters were assessed according to the standard WHO criteria. The present study revealed an abnormal biphasic profile of MIF in the seminal fluid of individuals with impaired sperm parameters, which was either significantly below or above the range of MIF tautomarase activity typical of normal fertile men (p < 0.000). This is the first report in a Sri Lankan population. The receiver operating characteristic (ROC) plot analysis established a cutoff point of 3.375 μg MIF/mL of semen (at 90 % sensitivity: 81.2 % specificity; 0.923 accuracy) to differentiate fertile from infertile males (excluding azoospermics and severe oligozoospermics). The MIF concentrations significantly correlated with the semen pH in the azoospermic and severe oligozoospermic group. As MIF was clearly indicative of the male fertility status by estimates of sensitivity and specificity of the D-dopachrome tautomerase assay, MIF may be developed as a potential marker of male infertility in Sri Lanka.
... Most studies focus on the sperm morphology and motility. [2][3][4][5][6][7][8] However, ejaculated semen can be divided into 2 major components with differential centrifugation: sperm cells (spermatozoa) and the aqueous phase, which is also known as seminal plasma. Seminal plasma reflects secretions from the testis, epididymis, seminal vesicles, prostate, and bulbourethral glands. ...
... 12,14 Seminal Peptides and Male Fertility Several studies have identified and investigated peptides present in seminal plasma that are involved in sperm motility and thereby fertility. [2][3][4]10,[15][16][17][18][19][20] Although it is recognized that seminal peptides affect sperm motility, the precise role of individual peptides is minimally understood. The rapidly growing number of peptides identified in the seminal plasma peptidome introduces an additional level of challenge for researchers interested in characterizing the role of individual seminal proteins in male fertility. ...
... 3 Dysregulation of macrophage migration inhibitory factor (MIF), a ubiquitous cytokine, adversely affects fertility through effects on human sperm maturation and motility. 2 Aljabari et al reported a correlation between MIF levels in human seminal fluid and fertility status. They found an abnormal biphasic profile of MIF in the seminal fluid of patients with impaired sperm parameters. ...
Infertility is a devastating medical condition that adversely affects emotional health and well-being of couples who desire pregnancy and parenthood. The overall demographic data suggest that the indication for more than one-third of assisted reproductive technology cycles performed in the United States includes male factor infertility. There is increasing recognition of the role that peptides present in seminal plasma have in determining sperm motility. Several recent studies suggest that peptidases, such as neutral endopeptidase (NEP) and aminopeptidase N (APN), impose significant adverse effects on sperm motility. Interestingly, several recent studies demonstrate that there is an endogenous NEP/APN inhibitor peptide called opiorphin in human seminal plasma. Our pilot studies suggest opiorphin promotes sperm motility and may positively influence sperm motility parameters in some cases of males infertility characterized by asthenozoospermia.
... There is a negative correlation between the amount of sperm-associated MIF and sperm motility (Frenette et al., 2005). MIF inhibits motility, increases phosphatidylserine externalization and DNA fragmentation of normal spermatozoa in vitro (Aljabari et al., 2007). The detrimental effect of MIF on sperm motility was confirmed by other authors, but only at high concentrations (Carli et al., 2007). ...
The role of inflammation and/or infection of the male accessory sex glands is very important for the potential effects that these conditions have on male fertility. The clinical Andrologist should be aware of the pathophysiological role of the main determinants of sperm damage when these conditions occur, in particular seminal leukocytes, oxidative stress, and cytokines. In addition, it is important to have a good knowledge of the methodologies to be used in the clinical practice. This article summarizes the methods used to look for and to identify the microorganisms responsible for male urogenital tract infections. These include sperm culture, urine culture, urethral swab, Meares-Stamey test, and balanopreputial swab. In the last part, we discussed the role of human papillomavirus (HPV) infection in male infertility.
... There is a negative correlation between the amount of sperm-associated MIF and the percentage of motility (Frenette et al., 2005). In addition, normal spermatozoa incubated with MIF exhibit decreased motility, increased phosphatidylserine (PS) externalization and increased DNA fragmentation (Aljabari et al., 2007). Carli et al. reported that MIF inhibits sperm motility, but only at high concentrations (Carli et al., 2007a,b). ...
Understanding semen markers of inflammation is important for the diagnostic-therapeutic management of male infertility, particularly in patients with male accessory gland infection (MAGI). The aim of this article was to describe the major pathophysiological elements through which inflammation negatively affects sperm parameters. Inflammation may affect reproduction through one or more of the following mechanisms: anatomical alteration of the male accessory gland (e.g., obstruction or sub-obstruction); functional alteration of the male accessory gland, i.e., by inhibiting the production of adequate amounts of nutrients and/or by releasing compounds such as radical oxygen species (ROS) and cytokines that alter the microenvironment in which spermatozoa develop and mature; and/or direct negative effects on the spermatozoa (germ-spermatozoa interaction).
... Fizyolojik konsantrasyonlarda sperm kapasitasyonunda rol oynayan MIF'in yüksek konsantrasyonlarda sperm motilitesine negatif etkisinin olduğu gösterilmiştir. Normal spermlere MIF eklendiğinde ise ileri hareketliliğin azaldığı ve DNA kırıklarının arttığı tespit edilmiştir (111,112). ...
... We have shown a negative correlation between MIF levels in human seminal fluid and fertility status. In addition, MIF added to normal spermatozoa decreased total sperm and progressive motility and increased the percentage of spermatozoa with PS externalization or with DNA fragmentation (Aljabari et al., 2007). A deleterious effect on sperm motility was also reported although only at high concentrations, whereas MIF may play a physiological role in sperm capacitation process at lower concentrations (Carli et al., 2007). ...
Male accessory gland infection (MAGI) has been identified among those diagnostic categories which have a negative impact on the reproductive function and fertility in males (Rowe et al., World Health Organization Manual for the Standardised Investigation and Diagnosis of the Infertile Couple, Cambridge University Press, Cambridge, 1993). MAGI is a hypernym which groups the following different clinical categories: prostatitis, prostate-vesiculitis and prostate-vesiculo-epididymitis. Some of the characteristics they share are: common diseases, mainly have a chronic course, rarely cause obstruction of the seminal pathways, can have an unpredictable intracanicular spread to one or more sexual accessory glands of the reproductive tract, as well as to one or both sides. In this review, we show that all components involving the inflammatory response (from the agents which first trigger it to each component of the inflammatory response dynamic) can deteriorate conventional and/or non-conventional sperm parameters arising from one or more of the following mechanisms: altered secretory function of the epididymis, seminal vesicles, and prostate which reduce the antioxidant properties or scavenging role of the seminal plasma; deterioration of spermatogenesis; and (unilateral or bilateral) organic or functional sub-obstruction of the seminal tract.
