Creatine as a Promising Component of Paternal Preconception Diet

Male fertility has been declining globally over the past several decades, advancing from a personal issue to a public health problem. Beyond any doubt, a reduction in fertility (often characterized by low sperm count or motility) can severely threaten reproductive health and lifecourse framework in a long-term fashion. Aside from uncovering the currently unknown etiology of modern-day male infertility, the scientific and medical community faces a double burden: finding an efficient biomarker of impaired fertility and exploring any intervention that can act to enhance fertility. A plethora of nutritional compounds have been recognized as possible modulators of semen quality, and specific dietary patterns and nutrients appear to be accompanied by a lower risk of male infertility. Creatine, a conditionally essential nutrient, has caught attention as a male fertility-promoting candidate due to its role in sperm energy metabolism. This mini-review describes the creatine-related bioenergetics of spermatozoa, explores a connection between creatine levels and sperm quality in men, and critically examines available evidence for interventional studies with creatine to affect sperm viability.     

Adding bovine seminal plasma prior to freezing improves post-thaw bull sperm kinematics but decreases mitochondrial activity

Variations in fertility between bulls with comparable sperm quality could be due to differences in their seminal plasma (SP). The aim of this study was to investigate the effect of adding bovine SP from bulls of known fertility to SP-free sperm samples. After removal of SP by Single Layer Centrifugation, resuspended sperm pellets were treated with SP from high or low fertility bulls at 0% (control), 1%, or 5% before freezing. Sperm quality was evaluated after thawing. Data were analyzed using Proc MIXED, SAS®. Bovine SP at 1% or 5% SP1 and SP5, respectively, decreased average path velocity, curvilinear velocity, and amplitude of lateral head displacement whereas wobble and linearity were increased. In addition, the proportion of spermatozoa with high mitochondrial membrane potential (MMP) was lowest for treatment with SP5 compared to SP1 and control. The proportion of SP did not affect other parameters of sperm quality. Thus, adding 5% bovine SP produced a favorable effect on some sperm velocity parameters but had an unfavorable effect on MMP. There were no differences in effect between SP from high and low fertility bulls.

Abbreviations: AI: artificial insemination; BCF: beat cross frequency; CASA: computer-assisted sperm analysis; IVF: in vitro fertilization; MMP: mitochondrial membrane potential; SLC: single layer centrifugation; SP: seminal plasma     

广西地区正常生育力男性精液质量的调查分析

目的了解广西地区正常生育力男性的精液质量状况。方法选择广西地区有生育力的男性进行精液检测,对精液的各主要参数进行分析,比较壮族和汉族不同居住地间的差别。结果 687例正常生育力男性的精子密度、存活率、精液量和pH值与世界卫生组织(World Health Organization,WHO)——第4版的正常参考值符合率较高,液化时间、正常精子形态率和活动力的符合率偏低。其中有321例(46.72%)达到世界卫生组织的精液分析正常值标准。汉族正常精子形态率则低于壮族,差异具有统计学意义(P<0.05)。居住在农村的男性和城市的相比较,除pH值无明显差异(P>0.05)外,其他参数均明显优于城市,差异有统计学意义(P<0.05)。结论广西地区正常生育力男性的精液参数与国内其他调查分析结果相似;广西汉族、壮族间精液质量差别不大,农村男性的精液质量优于城市男性。     

Profiling of sperm proteins and association of sperm PDC-109 with bull fertility

Abstract

The composition of sperm proteins influences the fertilizing ability of sperm and hence the present study was conducted (i) to profile sperm proteins expression patterns in bulls of differing fertility index and (ii) to identify and relate the abundant sperm proteins with bull fertility. The semen samples were collected from Holstein-Friesian bulls (n?=?12) varying in conception rate (CR) (high/low). The frozen semen straws (three ejaculates, from each bull) were used to study (a) sperm kinetic parameters, (b) plasmalemma integrity, (c) mitochondrial membrane potential, and (d) chromatin distribution. Three bulls were randomly selected from each group (n?=?3) and the neat sperm pellets were subjected to percoll purification, followed by protein isolation using 0.1% Triton X100. The sperm kinetic parameters, plasmalemma integrity, mitochondrial membrane potential, and the chromatin distribution did not differ significantly between groups. The number of acidic (pI; 3.1–5.6, 37%) and basic (pI; 7.9–10.0, 27%) proteins and their pattern of expression varied significantly (p?<?0.05) between high and low fertile bulls. The abundant sperm protein spots in 2D-gel electrophoresis (2DE) were identified as seminal plasma protein PDC-109 (i.e., protein with N-terminus aspartic acid, D and carboxy terminus cystine, having 109 amino acids) and its isoform and spermadhesin-1 (SPADH1). The western blot analysis confirmed the presence of PDC-109 isoform proteins at 15.4?kDa (pI 5.3 and 5.5). The seminal plasma protein PDC-109 was abundant in the low fertile when compared to the high fertile group (p?<?0.05). This study suggests that the imbalance in acidic and basic sperm proteins may influence sperm fertility and sperm PDC-109 levels above a certain threshold affects bull fertility.     

The effects of smoking on fertility from gametogenesis to implantation

The literature concerning the effects of cigarette smoking, treatment with nicotine, cigarette smoke condensates, or cigarette smoke constituents on reproductive events from gametogenesis to implanatation is reviewed. Epidemiologic evidence, although scanty, suggests that cigarette smoking decreases fertility in women. Cigarette smoking is also associated with an increased frequency of menstrual abnormalities and a cigarette dose-related decrease in the age of spontaneous menopause. Similar epidemiologic studies assessing reproductive function have not been conducted among men who smoke. Several small studies have demonstrated decreased sperm counts and an increased frequency of abnormal sperm morphology among male smokers. Cessation of smoking in several of these studies has been associated with an increase in sperm number and a decrease in the frequency of sperm shape abnormalities. Treatment of rodents with cigarette smoke or cigarette smoke constituents produces similar effects on sperm number and morphology. Experimental evidence from humans and rodents suggests that cigarette smoke or nicotine can alter hypothalamic-pituitary interrelationships, stimulating growth hormone, cortisol, vasopressin, and oxytocin release and inhibiting luteinizing hormone and prolactin release. These changes may alter hormonal interrelationships necessary for successful reproduction. Studies in rodents and human and nonhuman primates also suggest that cigarette smoke or nicotine alters the motility of the female reproductive tract, and may impair implantation of the embryo. Analysis of the experimental data available concerning the effects of smoking on reproductive processes suggests an adverse influence on reproduction at several sites from gametogenesis to implantation. The literature on smoking and fertility, however, is surprisingly small. Additional experimentation, as well as epidemiological surveys of human populations, are necessary before it will be possible to make unequivocal statements concerning reproductive interference by cigarette smoke or its components.     

Cyanidin-3-O-Glucoside Supplement Improves Sperm Quality and Spermatogenesis in a Mice Model of Ulcerative Colitis

Impaired fertility and low sperm quality are the global health problem with high attention. It has been noted that inflammation may impact fertility by affecting testicular spermatogenesis. Cyanidin-3-O-glucoside is a natural functional pigment with various health benefits. Nevertheless, studies on the mechanism by which C3G protects male reproduction in mice with ulcerative colitis remain scarce. The purpose of this study is to illustrate the potential mechanism of C3G for improving impaired fertility caused by colitis. A DSS-induced colitis model was applied to assess the effects of sperm quality with colitis and the health benefit role of C3G. Results indicated that C3G-treated mice exhibited higher body weight, longer colon length, less crypt damage and focal inflammation infiltration. Being consistent with that, low sperm count, low testis weight, high inflammation levels and abnormal thickness of seminiferous epithelium also observed in the DSS group were significantly recovered upon C3G treatment. These findings suggested that colitis has a close link to impaired fertility. Further analysis found that C3G could significantly suppress the inflammatory mediators in serum. Results conjointly indicated that C3G might improve the impaired fertility of mice with colitis by inhibiting inflammatory cytokines through the blood–testis barrier. C3G could be a promising daily supplement for ameliorating impaired fertility caused by colitis.     

High Resolution Light Microscopic Evaluation of Boar Semen Quality Sperm Cytoplasmic Droplet Retention in Relationship with Boar Fertility Parameters

The purpose of this study was to investigate the relationship between fertility and quantitative measures of boar semen quality, including various patterns of sperm cytoplasmic droplet (CD) retention, as determined by high power differential interference contrast (DIC) microscopy. A total of 116 ejaculates were collected from a nucleus herd of 18 Large White boars over an eight month period. Semen quality parameters were analyzed for each ejaculate by calculating the percentage of normal spermatozoa, spermatozoa possessing a CD in the proximal, distal, or distal midpiece reflex position, total spermatozoa with an attached cytoplasmic droplet, spermatozoa with non-CD related aberrations and total spermatozoa with abnormalities. Of the 116 ejaculates received, 71 ejaculates from 13 boars had corresponding fertility data from single-sire inseminations of multiparous sows. The fertility data included farrowing rate (FR) and total number born (TNB). The monthly FR encompassed one month before and one month after the date of semen collection. Detection of differences for fertility and semen quality parameters was performed by separating the boars into either an above-average or below-average group based on the mean FR (74.01 ± 1.43%) or TNB (12.34 ± 0.17) for the study. For FR, the boars in the below-average group had a significantly lower percentage of normal spermatozoa and significantly higher percentage of spermatozoa possessing distal CDs, total attached CDs and total abnormalities compared to the boars in the above-average group. Conversely, for TNB there were no significant differences between the above- and below-average groups for the semen quality parameters. These data suggest that the attached CD may negatively affect FR, but not TNB. The detection of relationships between the boar fertility parameters and the retention of the sperm CD after ejaculation, document the advantage of high power DIC microscopy in conventional semen evaluation.     

Effect of occupational exposures on male fertility: literature review

The present review was aimed to determine the influence of working conditions, occupational exposures to potential chemical and physical reproductive toxic agents and psychological stress during work on male fertility. Significant associations were reported between impaired semen parameters and the following chemical exposures: metals (lead, mercury), pesticides (dibromochlorophane, 2,4-dichlorophenoxyacetic acid), ethylene glycol ethers and estrogens. The following physical exposures were shown to deteriorate sperm parameters: radiation (both ionized and microwaves) and heat. Psychological distress has another important contribution to infertility. Several studies indicated that stress has a negative impact on sperm parameters. Occupational parameters should be an important part of history taking among patients attending infertility clinics.     

A review of the effect of pesticide formulations on male fertility

Experimental studies suggest that large numbers of chemicals, environmental and industrial pollutants affect the male reproductive system. At present, almost no information is available on the effects of these adverse agents on human reproduction. Recent reports, however, suggest that in the past 50 years male fertility has declined based on qualitative and quantitative measurements of normal sperm. This study identifies‐among the active ingredients and solvents included in pesticide formulations registered in Italy‐the chemical agents with experimental evidence of male reproductive toxicity. Documents produced by international agencies and organizations such as IARC, EPA, WHO, and original papers from the international literature were systematically reviewed. The results indicate that several pesticide products notified in the Italian Registry contain active ingredients and/or solvents severely affecting testicular function and sperm morphology in laboratory animals. Therefore, exposure to reproductive toxicants occurring among manufacturers and users of pesticide formulations registered in Italy suggest further epidemiologic surveys should be conducted in this area.     

Ambient air pollution exposure and damage to male gametes: human studies and in situ ‘sentinel’ animal experiments

Globally there is concern that adverse reproductive outcomes and fertility impairment in humans may be caused by exposure to environmental contaminants. Air pollution in particular has been linked to DNA damage, abnormal sperm morphology, and reduced sperm performance in men. Experimental studies using model species (mice and rats) exposed in situ provide evidence that ambient air pollution can cause damage to the respiratory system and other tissues or organs. This can take the form of DNA damage and other genetic changes throughout the body, including induced mutations, DNA strand breaks, and altered methylation patterns in male germ cells. Human and animal studies together provide strong evidence that air pollution, especially airborne particulate matter, at commonly occurring ambient levels is genotoxic to male germ cells. The mechanistic link between air pollution exposure and induced genetic changes in male germ cells is currently unclear. ‘Sentinel’ animal experiments explicitly examining air pollution affects on sperm quality in laboratory rodents have not been conducted and would provide a critical link to observations in humans. The importance of air pollution compared to other factors affecting fertility and reproductive outcomes in humans is not clear and warrants further investigation.     

Biologically infallible? Men’s views on male age-related fertility decline and sperm freezing

Trends in people having children later in life and increasing evidence of male age-related fertility decline (ARFD) has led some to propose sperm freezing as a suitable response. However, little consideration has been given to how men might respond to such a proposal, and there has been a paucity of empirical data to inform such a consideration. This paper arises from in-depth, semi-structured interviews with men (n = 25) who do not have children but want or expect to have them in the future. Data on men’s perceptions of male ARFD and sperm freezing are presented and discussed in accordance with theoretical and conceptual tools relating to reproductive masculinity, biomedicalisation, gendered risk perception and meanings of sperm and masculinity. It suggests that that men’s overall lack of concern regarding male ARFD and resistance towards ideas of sperm freezing result not only from a lack of exposure to evidence regarding male ARFD but are also shaped by ideals of reproductive masculinity, and may indicate resistance towards the idea of reproductive control. It argues that these positions perpetuate a gender unequal politicisation of ARFD and perpetuate particular gendered subjectivities relating to culpability and responsibility for guarding against risks of ARFD.     

Loss of livestock breeding efficiency due to uncompensable sperm nuclear defects

An important goal of modern analyses of semen is to elucidate the molecular traits of mammalian sperm chromatin structural abnormalities, defined here as 'uncompensable', that lead to abnormalities in fertility, pronuclear formation, early embryo quality and pregnancy outcome. Sperm with uncompensable nuclear abnormalities are able to fertilize oocytes both in vivo and in vitro; however, due to the uncompensable trait(s), the embryo development may be abnormal. Uncompensable nuclear traits can be experimentally induced in bull sperm by a mild thermal insult to the testis. Sperm nuclear morphology abnormalities seen in ejaculates 11-days post stress are likely related to molecular changes in chromatin observed 3-days post stress by the flow cytometric sperm chromatin structure assay (SCSA). The SCSA measures the susceptibility of sperm nuclear DNA to denaturation in situ. This susceptibility has been correlated with the presence of DNA strand breaks that may be derived in part by oxidative stress and possibly by a unique, abortive apoptotic mechanism. The extent of DNA denaturation is not significantly related to the level of disulfide bonding between the chromatin protamines. The use of human sperm with uncompensable nuclear traits for artificial reproductive techniques is also discussed. The goal of this research is to remove from semen doses those sperm with uncompensable nuclear traits and thereby increase male fertility potential.     

Testicular apoptosis after dietary zinc deficiency: Ultrastructural and TUNEL studies

The present study was conducted in Wistar rats to determine whether prepubertal dietary zinc deficiency causes apoptotic changes in testes. Prepubertal male Wistar rats (40–50 gm) were divided into 3 groups: zinc control (ZC), pairfed (PF), and zinc deficient (ZD). Control and pairfed groups were given a 100 ppm zinc diet while the deficient groups received 1 ppm zinc diet for 2 and 4 weeks (w), respectively. Ultrastructural studies revealed several apoptotic features such as wavy basement membrane, displaced nuclei, chromatin condensation, plasma membrane blebbing, nuclear membrane dissolution, loss of inter-Sertoli cell junctional complexes, and intercellular bridges and deformed mitochondria. A variable spectrum of sperm defects had also been visualized e.g., acrosomal deformities such as decapitation and a ring of condensed chromatin around the nuclear periphery, deformed sperm heads with a condensed nucleus, tail-elements with superfluous cytoplasm, and damage to the mitochondrial sheath and aggregation of spermatozoa within the membrane. This was further supported by TUNEL studies. Apoptotic index, epididymal sperm concentration, motility, and fertility index also revealed a significant (P?<?0.05) decrease in zinc deficient groups (2 and 4 w) when compared with their respective control and pairfed groups. All the above findings are indicative that changes observed in the testes after dietary zinc deficiency are due to the onset of apoptosis. Increased apoptotic degeneration in testes may cause irreversible changes in the germ cells associated with decreased epididymal sperm concentration, motility, and fertility index which contributes to the low efficiency of spermatogenesis thereby indicating a possible role of zinc in fertility.     

Procedures for fertility preservation in female cancer patients

Improving survival rates and quality of life following modern combined cancer treatments have resulted a growing number of patients requesting maintenance of reproductive functions. Several methods are currently available to maintain fertility during oncotherapy. Even though most of them are still experimental and their efficacy and safety have not been determined, the future for fertility preservation in women with cancer is promising. In vitro fertilization with embryo cryopreservation offers an established method, but time to delay cancer treatment could be risky regarding the progression of several cancer types. Moreover, exposure to a high oestrogen milieu during ovarian stimulation is undesirable when patients have estrogen-sensitive malignant tumours. Cryopreservation of mature oocytes following in vitro fertilization and intracytoplasmatic sperm injection offers advantages, but it is still limited due to its low success rate. Emerging techniques of ovarian tissue cryopreservation followed by autotransplantation have been clinically explored. Novel technologies of tissue freezing and thawing promise improving results. However, only one live birth following autotransplanted frozen-thawed ovarian tissue has been established. This procedure can be offered in the future for prepubertal girls before cancer treatment to maintain future fertility. Gonadal tissue cryopreservation and transplantation should be considered experimental in humans for the present time until greater evidence regarding efficacy and safety is accrued.     

FROM ZERO TO ONE HUNDRED MILLION IN SIX MONTHS: THE TREATMENT OF AZOOSPERMIA IN CONGENITAL ADRENAL HYPERPLASIA

In the majority of the 25% of couples in which a male factor is responsible for their infertility, no identifiable pathology is found. It is unusual to be faced with an etiology that is readily amenable to successful treatment without the eventual dependence on assisted reproductive techniques for pregnancy. The diagnosis of congenital adrenal hyperplasia has variable implications on fertility. A case is presented of azoospermia in a man diagnosed with classical non-salt-losing congenital adrenal hyperplasia. Within 9 months of treatment with dexamethasone, his sperm count had risen to above 100 million per milliliter, enough to overcome very poor morphology and a naturally conceived pregnancy ensued. The pregnancy is ongoing. Although an increase in sperm count has been shown in such cases, the degree of improvement in semen parameters is unique, especially in an azoospermic patient.     

Computer-assisted sperm analysis parameters in young fertile sperm donors and relationship with age

Sperm parameter values have been shown to decline with age, according to conventional sperm analysis. However, the effect of age on sperm kinematic parameters has been rarely studied, especially in young fertile men. Here, we studied Computer-Assisted Sperm Analysis (CASA) parameters in a large cohort of men with proven fertility, in order to determine if there is a decline with age in this young fertile population. This retrospective analysis of CASA parameters was conducted on all donors included in the sperm donor programme in the Assisted Reproductive Techniques (ART) Centre of the University Hospital of Nantes between 2006 and 2009. Sperm concentration, motility, and kinetic parameters were recorded by a HTM-Ceros system and compared in 3 groups of sperm donors according to their age:?<35 years, 36–40 years, and 41–44 years. A total of 362 ejaculates from 138 donors were analyzed. Values for ALH, VCL, LIN, and STR significantly decreased with age. Sperm concentration, motile sperm proportion, and other kinetic parameters did not differ significantly among the groups. The use of CASA allowed the identification of ALH, VCL, LIN, and STR age-related decrease in young men with proven fertility.     

Computer-assisted sperm analysis parameters in young fertile sperm donors and relationship with age

Sperm parameter values have been shown to decline with age, according to conventional sperm analysis. However, the effect of age on sperm kinematic parameters has been rarely studied, especially in young fertile men. Here, we studied Computer-Assisted Sperm Analysis (CASA) parameters in a large cohort of men with proven fertility, in order to determine if there is a decline with age in this young fertile population. This retrospective analysis of CASA parameters was conducted on all donors included in the sperm donor programme in the Assisted Reproductive Techniques (ART) Centre of the University Hospital of Nantes between 2006 and 2009. Sperm concentration, motility, and kinetic parameters were recorded by a HTM-Ceros system and compared in 3 groups of sperm donors according to their age:?<35 years, 36-40 years, and 41-44 years. A total of 362 ejaculates from 138 donors were analyzed. Values for ALH, VCL, LIN, and STR significantly decreased with age. Sperm concentration, motile sperm proportion, and other kinetic parameters did not differ significantly among the groups. The use of CASA allowed the identification of ALH, VCL, LIN, and STR age-related decrease in young men with proven fertility.     

Citrus limon extract: possible inhibitory mechanisms affecting testicular functions and fertility in male mice

The effect of oral administration of 50% ethanolic leaf extract of Citrus limon (500 and 1,000?mg/kg body weight/day) for 35 days on fertility and various male reproductive endpoints was evaluated in Parkes strain of mice. Testicular indices such as histology, 3β- and 17β-HSD enzymes activity, immunoblot expression of StAR and P450scc, and germ cell apoptosis by TUNEL and CASP- 3 expression were assessed. Motility, viability, and number of spermatozoa in the cauda epididymidis, level of serum testosterone, fertility indices, and toxicological parameters were also evaluated. Histologically, testes in extract-treated mice showed nonuniform degenerative changes in the seminiferous tubules. Treatment had adverse effects on steroidogenic markers in the testis and induced germ cell apoptosis. Significant reductions were noted in epididymal sperm parameters and serum level of testosterone in Citrus-treated mice compared to controls. Fertility of the extract-treated males was also suppressed, but libido remained unaffected. By 56 days of treatment withdrawal, alterations induced in the above parameters returned to control levels suggesting that Citrus treatment causes reversible suppression of spermatogenesis and fertility in Parkes mice. Suppression of spermatogenesis may result from germ cell apoptosis because of decreased production of testosterone. The present work indicated that Citrus leaves can affect male reproduction.     

精液质量评估与男性生育力关系

目的不育夫妇中,50%与男性因素相关,随着不育症的发病率增高,对男性生育力的正确评估显得尤为重要。《世界卫生组织人类精液检查与处理实验室手册》的更新不断推动着男科实验室的发展,也提出了问题与挑战。正确认识精液质量评估的各种参数与男性生育力之间的关系对临床诊断以及治疗方案的选择至关重要。     

Effects of prolonged autovehicle driving on male reproductive function: A study among taxi drivers

This study had the purpose of exploring the possible association between the work exposures of professional drivers and their reproductive health, by studying a group of 201 taxi drivers in the city of Rome. Data on work and reproductive history were collected by interviews. Biological markers examined in 72 subjects included salivary testosterone levels, sperm quality (i.e., sperm concentration, sperm morphology, and motility), and fertility experience, including time to pregnancy. Their spermatologic profile was compared with that of a control group of 50 healthy subjects of similar age and smoking habits. The results showed that taxi drivers, compared to the controls, had a significantly lower prevalence of normal sperm forms (45.8% vs. 64.0%); this was particularly true for those with a longer time on this job. This result was confirmed by a multivariate analysis in which confounders such as age, smoking, and alcohol consumption were controlled. The other sperm parameters did not differ in the study and the control groups. Among the life-style factors, we found smoking to be associated with poorer sperm morphology. Moderate alcohol consumption was associated with a better seminologic profile, while the pattern in respect to coffee intake was inconclusive. Subjects with poor semen quality also more frequently exhibited longer time to pregnancy of their partner. The results suggest that prolonged urban automobile driving might be a risk factors for sperm quality, and particularly for sperm morphology, but the finding needs further confirmation. © 1996 Wiley-Liss, Inc.