Impaired Male Fertility Research Articles

From sperm to offspring: Assessing the heritable genetic consequences of paternal smoking and potential public health impacts.

Individuals who smoke generally do so with the knowledge of potential consequences to their own health. What is rarely considered are the effects of smoking on their future children. The objective of this work was to review the scientific literature on the effects of paternal smoking on sperm and assess the consequences to offspring. A literature search identified over 200 studies with relevant data in humans and animal models. The available data were reviewed to assess the weight of evidence that tobacco smoke is a human germ cell mutagen and estimate effect sizes. These results were used to model the potential increase in genetic disease burden in offspring caused by paternal smoking, with specific focus on aneuploid syndromes and intellectual disability, and the socioeconomic impacts of such an effect. The review revealed strong evidence that tobacco smoking is associated with impaired male fertility, and increases in DNA damage, aneuploidies, and mutations in sperm. Studies support that these effects are heritable and adversely impact the offspring. Our model estimates that, with even a modest 25% increase in sperm mutation frequency caused by smoke-exposure, for each generation across the global population there will be millions of smoking-induced de novo mutations transmitted from fathers to offspring. Furthermore, paternal smoking is estimated to contribute to 1.3 million extra cases of aneuploid pregnancies per generation. Thus, the available evidence makes a compelling case that tobacco smoke is a human germ cell mutagen with serious public health and socio-economic implications. Increased public education should be encouraged to promote abstinence from smoking, well in advance of reproduction, to minimize the transmission of harmful mutations to the next-generation.

MONENSIN SENSITIVITY1 (MON1)/CALCIUM CAFFEINE ZINC SENSITIVITY1 (CCZ1)-Mediated Rab7 Activation Regulates Tapetal Programmed Cell Death and Pollen Development

Programmed cell death (PCD)-triggered degradation of plant tapetum is essential for microspore development and pollen coat formation; however, little is known about the cellular mechanism regulating tapetal PCD Here, we demonstrate that Rab7-mediated vacuolar transport of tapetum degradation-related cysteine proteases is crucial for tapetal PCD and pollen development in Arabidopsis (Arabidopsis thaliana), with the following evidence: (1) The monensin sensitivity1 (mon1) mutants, which are defective in Rab7 activation, showed impaired male fertility due to a combined defect in both tapetum and male gametophyte development. (2) In anthers, MON1 showed preferential high level expression in tapetal cell layers and pollen. (3) The mon1 mutants exhibited delayed tapetum degeneration and tapetal PCD, resulting in abnormal pollen coat formation and decreased male fertility. (4) MON1/CALCIUM CAFFEINE ZINC SENSITIVITY1 (CCZ1)-mediated Rab7 activation was indispensable for vacuolar trafficking of tapetum degradation-related cysteine proteases, supporting that PCD-triggered tapetum degeneration requires Rab7-mediated vacuolar trafficking of these cysteine proteases. (5) MON1 mutations also resulted in defective pollen germination and tube growth. Taken together, tapetal PCD and pollen development require successful MON1/CCZ1-mediated vacuolar transport in Arabidopsis.

Association of anti-sperm antibodies with chronic prostatitis: A systematic review and meta-analysis

Chronic prostatitis is a risk factor for impaired male fertility potential, and anti-sperm antibodies (ASAs) cause the autoimmune disease immune infertility, which has a negative effect on semen parameters. Current studies have investigated the ASA-positive relationship between chronic prostatitis versus normal controls, but have shown inconsistent results. Hence, we systematic searched the PubMed, EMBASE, Science Direct/Elsevier, Medline, and the Cochrane Library up to October 2015 for case-control studies that involved the ASA-positive relationship between chronic prostatitis patients versus normal controls. The meta-analysis was performed with Review Manager and Stata software. After literature search, six studies were identified, including 721 cases of chronic prostatitis and 160 normal controls. Our results illustrated a significant correlation of the ASA-positive relationship between chronic prostatitis patients versus normal controls. The combined odds ratio of the ASA-positive rate in chronic prostatitis patients and normal controls was 3.26 (1.86–5.71). There was also a significant correlation of the ASA-positive relationship between National Institutes of Health (NIH) III versus normal controls, and the combined OR was 2.46 (1.10–5.51). However, there was no significant correlation of the ASA-positive relationship between National Institutes of Health (NIH) II versus normal controls. The present study illustrates that the positive rate of ASAs in chronic prostatitis patients was significantly higher than in the control group, suggesting that chronic prostatitis has a negative effect on male reproductive function. However, studies with larger samples are needed to better illuminate the correlation between ASAs and chronic prostatitis.

Brown adipose tissue transplantation ameliorates male fertility impairment caused by diet-induced obesity

Populations with obesity or overweight have a high incidence of infertility. We hypothesised that brown adipose tissue (BAT) transplantation can attenuate the impairment of male fertility caused by diet-induced obesity. BATs were transplanted from male donor mice into age and sex matched recipient mice fed high-fat diets (HFD). Sperm motility experiment was conducted after surgical procedure. X-ray computed tomography scanning, biochemical assay, real-time PCR and western blot analysis were performed. BAT transplantation reduced body fat and epididymal fat mass, as well as triglycerides (TG) content in testis and epididymis and total cholesterol (TCHO) contents in epididymis compared with the HFD group. Sperm motility and progressiveness were recovered and mRNA and protein levels of genes related to sperm motility such as cullin 3 (Cul3), peroxisome proliferator activated receptor alpha (PPARα) and its down-stream genes were significantly down-regulated post BAT transplantation. BAT transplantation partially ameliorated impairment of male fertility caused by diet-induced obesity.

The status of sperm immobilizing-antibody (SI-Ab) detected in infertile females (therapy and pathogenic mechanisms)

Chronic prostatitis is a risk factor for impaired male fertility potential, and anti-sperm antibodies (ASAs) cause the autoimmune disease immune infertility, which has a negative effect on semen parameters. Current studies have investigated the ASA-positive relationship between chronic prostatitis versus normal controls, but have shown inconsistent results. Hence, we systematic searched the PubMed, EMBASE, Science Direct/Elsevier, Medline, and the Cochrane Library up to October 2015 for case-control studies that involved the ASA-positive relationship between chronic prostatitis patients versus normal controls. The meta-analysis was performed with Review Manager and Stata software. After literature search, six studies were identified, including 721 cases of chronic prostatitis and 160 normal controls. Our results illustrated a significant correlation of the ASA-positive relationship between chronic prostatitis patients versus normal controls. The combined odds ratio of the ASA-positive rate in chronic prostatitis patients and normal controls was 3.26 (1.86–5.71). There was also a significant correlation of the ASA-positive relationship between National Institutes of Health (NIH) III versus normal controls, and the combined OR was 2.46 (1.10–5.51). However, there was no significant correlation of the ASA-positive relationship between National Institutes of Health (NIH) II versus normal controls. The present study illustrates that the positive rate of ASAs in chronic prostatitis patients was significantly higher than in the control group, suggesting that chronic prostatitis has a negative effect on male reproductive function. However, studies with larger samples are needed to better illuminate the correlation between ASAs and chronic prostatitis.

The relationship between sperm viability and DNA fragmentation rates.

BackgroundIn humans, sperm DNA fragmentation rates have been correlated with sperm viability rates. Reduced sperm viability is associated with high sperm DNA fragmentation, while conversely high sperm viability is associated with low rates of sperm DNA fragmentation. Both elevated DNA fragmentation rates and poor viability are correlated with impaired male fertility, with a DNA fragmentation rate of > 30% indicating subfertility. We postulated that in some men, the sperm viability assay could predict the sperm DNA fragmentation rates. This in turn could reduce the need for sperm DNA fragmentation assay testing, simplifying the infertility investigation and saving money for infertile couples.MethodsAll men having semen analyses with both viability and DNA fragmentation testing were identified via a prospectively collected database. Viability was measured by eosin-nigrosin assay. DNA fragmentation was measured using the sperm chromosome structure assay. The relationship between DNA fragmentation and viability was assessed using Pearson’s correlation coefficient.ResultsFrom 2008-2013, 3049 semen analyses had both viability and DNA fragmentation testing. A strong inverse relationship was seen between sperm viability and DNA fragmentation rates, with r = -0.83. If viability was ≤ 50% (n = 301) then DNA fragmentation was ≥ 30% for 95% of the samples. If viability was ≥ 75% (n = 1736), then the DNA fragmentation was ≤ 30% for 95% of the patients. Sperm viability correlates strongly with DNA fragmentation rates.ConclusionsIn men with high levels of sperm viability ≥ 75%, or low levels of sperm viability ≤ 30%, DFI testing may be not be routinely necessary. Given that DNA fragmentation testing is substantially more expensive than vitality testing, this may represent a valuable cost-saving measure for couples undergoing a fertility evaluation.

Rhox8 Ablation in the Sertoli Cells Using a Tissue-Specific RNAi Approach Results in Impaired Male Fertility in Mice.

The reproductive homeobox X-linked, Rhox, genes encode transcription factors that are selectively expressed in reproductive tissues. While there are 33 Rhox genes in mice, only Rhox and Rhox8 are expressed in Sertoli cells, suggesting that they may regulate the expression of somatic-cell gene products crucial for germ cell development. We previously characterized Rhox5-null mice, which are subfertile, exhibiting excessive germ cell apoptosis and compromised sperm motility. To assess the role of Rhox8 in Sertoli cells, we used a tissue-specific RNAi approach to knockdown RHOX8 in vivo, in which the Rhox5 promoter was used to drive Rhox8-siRNA transgene expression in the postnatal Sertoli cells. Western and immunohistochemical analysis confirmed Sertoli-specific knockdown of RHOX8. However, other Sertoli markers, Gata1 and Rhox5, maintained normal expression patterns, suggesting that the knockdown was specific. Interestingly, male RHOX8-knockdown animals showed significantly reduced spermatogenic output, increased germ cell apoptosis, and compromised sperm motility, leading to impaired fertility. Importantly, our results revealed that while some RHOX5-dependent factors were also misregulated in Sertoli cells of RHOX8-knockdown animals, the majority were not, and novel putative RHOX8-regulated genes were identified. This suggests that while reduction in levels of RHOX5 and RHOX8 in Sertoli cells elicits similar phenotypes, these genes are not entirely redundant. Taken together, our study underscores the importance of Rhox genes in male fertility and suggests that Sertoli cell-specific expression of Rhox5 and Rhox8 is critical for complete male fertility.

Impact of Y chromosome AZFc subdeletion shows lower risk of fertility impairment in Siddi tribal men, Western Ghats, India.

BackgroundIndia is characterized by the presence of a large number of endogamous castes, tribes and religions, having second largest concentration of tribal population in the World with differed genetic ethnicity, lifestyle and environmental habitat from those of mainstream population. Lack of data is constraint when it comes to tracking the tribal population health status, specifically reproductive health aspects by experimental approaches. The male fertility impairment depends on Y chromosome azoospermia factor c (AZFc) subdeletions, which varies highly in different geographical populations and in an Indian admixed population the frequency and effect of deletion on fertility is relatively poorly documented. Therefore, the current study has been initiated to enumerate and characterize the strength of association between Yq11 AZFc subdeletions and fertility impairment among Siddi tribal men of Western Ghats, India.MethodsHere, using predesigned performa we collected personal as well as familial information of 200 volunteered male subjects and grouped them into: (i) 104 married individuals with proven fertility, and (ii) 96 unmarried men with unknown fertility status. Quantification of reproductive hormones such as follicle stimulating hormone (FSH), leutinizing hormone (LH) and testosterone were studied. Oxidative stress markers like total antioxidant capacity (TAC) and super oxide dismutase (SOD) along with analysis of five sequence tagged site (STS) hotspot markers were employed for mapping of Y chromosome AZFc subdeletions. Statistical analyses were performed using SPSS software.ResultsHormonal analysis and estimation of oxidative stress markers showed normal values with no significant differences between two subgroups. However, the Y chromosome AZFc subdeletion mapping revealed evident results as an individual displayed absence of STS sY1191 marker indicating b2/b3 deletion, whereas rest of the subjects exhibited no deletion for all the five STS markers. While, the individual has fathered two children, at this point it is difficult to draw a causal link between the observed deletion and its effect on fertility.ConclusionThus, our current study suggests that the association between AZFc subdeletions with its effect on infertility varies highly in this study cohort compared to other Indian ethnic groups, exhibiting lower risk factor and non-association reaching insignificance among Siddi tribal men.Electronic supplementary materialThe online version of this article (doi:10.1186/s12610-014-0017-5) contains supplementary material, which is available to authorized users.

Reproductive issues in sickle cell disease.

As medical advances improve survival, reduce disease-related morbidity, and improve quality of life, reproductive issues will take higher priority in the sickle cell disease (SCD) community. A wide variety of topics are addressed in this chapter, including fertility, gonadal failure, erectile dysfunction, and menstrual issues in SCD. Etiologies of impaired male fertility are multifactorial and include hypogonadism, erectile dysfunction, sperm abnormalities, and complications of medical therapies. Much less is known about the prevalence and etiology of infertility in women with SCD. Other reproductive issues in women included in this review are pain and the menstrual cycle, contraception, and preconception counseling. Finally, long-term therapies for SCD and their impact on fertility are presented. Transfusional iron overload and gonadal failure are addressed, followed by options for fertility preservation after stem cell transplantation. Focus is placed on hydroxyurea therapy given its benefits and increasing use in SCD. The impact of this agent on spermatogenesis, azoospermia, and the developing fetus is discussed.

Transgenerational impaired male fertility with an Igf2 epigenetic defect in the rat are induced by the endocrine disruptor p,p'-DDE.

What are the epigenetic mechanisms underlying the transgenerational effect of p,p'-DDE on male fertility? Impaired male fertility with an Igf2 epigenetic defect is transgenerationally inherited upon exposure of p,p'-DDE. p,p'-Dichlorodiphenoxydichloroethylene (p,p'-DDE) is one of the primary metabolite products of the ancestral organochlorine pesticide dichlorodiphenoxytrichloroethane. As it is a known anti-androgen endocrine disruptor, it could cause harmful effects on the male reproductive system. Pregnant rats (F0) were administered with p,p'-DDE or corn oil at the critical time of testis development, i.e. from gestation days 8 to 15. Male and female rats of the F1 generation were mated with each other to produce F2 progeny. To reveal whether the transgenerational phenotype is produced by the maternal or paternal line, F3 progeny were generated by intercrossing control (C) and treated (DDE) males and females of the F2 generation according to the following groups: (i) C♂-C♀, (ii) DDE♂-DDE♀, (iii) DDE♂-C♀ and (iv) C♂-DDE♀. Mature sperm and testes were collected from male offspring of the F1-F3 generations for the examination of male fertility parameters, i.e. sperm count and motility, testis histology and apoptosis. Expression of the imprinted genes, H19 and Igf2, was detected by real-time PCR. Igf2 DMR2 methylation was analyzed by bisulfite genomic sequencing. Upon exposure of p,p'-DDE, the male F1 generation showed impaired male fertility and altered imprinted gene expression caused by Igf2 DMR2 hypomethylation. These defects were transferred to the F3 generation through the male germline. This study has examined the effect of p,p'-DDE only on the sperm number and motility and the possible mechanism of Igf2 DMR2 methylation in vivo and thus has some limitations. Further investigation is necessary to focus on the epigenetic effects of p,p'-DDE at the genome level and to include a more detailed semen quality analysis including sperm morphology assessment. Impaired male fertility with epigenetic alterations is transgenerationally inherited after environmental exposure of p,p'-DDE, posing significant implications in the etiology of male infertility. The present research was supported by National Natural Science Fund for Young Scholar (81102161), the Natural Science Fund of Zhejiang Province (LY14H260004) and funding from the Health Department of Zhejiang Province (201475777). No competing interests are declared.

Interleukin-1β, cyclooxygenase-2, and hypoxia-inducible factor-1α in asthenozoospermia.

Impaired male fertility may have a variety of causes, among which asthenozoospermia. In its etiology, several bioactive substances, such as cytokines may be involved. In this context, our aim was to evaluate the expression of interleukin-1β, cyclooxygenase-2, and hypoxia-inducible factor-1α, in spermatozoa isolated from normospermic fertile donors and asthenozoospermic infertile patients. We evaluated twenty-eight infertile patients affected by idiopathic asthenozoospermia and twenty-three normospermic fertile donors, age-matched. Sperm parameters were evaluated; immunohistochemical analysis and enzyme-linked immunosorbent assay were then performed in isolated spermatozoa. Spermatozoa from the asthenozoospermic group presented an increased expression of IL-1β, COX-2, and HIF-1α compared with the normospermic fertile subjects. Our results can lead us to speculate that the increased expression of these substances may influence sperm motility. Nevertheless, further studies are needed in order to assess whether these bioactive mediators have a potential relevance as targets in future therapeutic strategies for the treatment of male infertility.

Upregulation and nuclear translocation of testicular ghrelin protects differentiating spermatogonia from ionizing radiation injury.

Proper control of apoptotic signaling is important for maintenance of testicular homeostasis after ionizing radiation (IR). Herein, we challenged the hypothesis that ghrelin, a pleiotropic modulator, is potentially involved in IR-induced germ cell injury. Lower body exposure to 2 Gy of IR induced a notable increase of ghrelin expression in the nuclear of differentiating spermatogonia at defined stages, with an impairment in the Leydig cells (LCs)-expressing ghrelin. Unexpectedly, inhibition of the ghrelin pathway by intraperitoneal injection of a specific GHS-R1α antagonist enhanced spermatogonia elimination by apoptosis during the early recovery following IR, and thereafter resulted in impaired male fertility, suggesting that the anti-apoptotic effects of evoked ghrelin, although transient along testicular IR injury, have a profound influence on the post-injury recovery. In addition, inhibition of ghrelin signaling resulted in a significant increase in the intratesticular testosterone (T) level at the end of 21 days after IR, which should stimulate the spermatogenic recovery from surviving spermatogonia to a certain extent during the late stage. We further demonstrated that the upregulation and nuclear trafficking of ghrelin, elaborately regulated by IR-elicited antioxidant system in spermatogonia, may act through a p53-dependent mechanism. The elicitation of ghrelin expression by IR stress, the regulation of ghrelin expression by IR-induced oxidative stress and the interaction between p53 and ghrelin signaling during IR injury were confirmed in cultured spermatogonia. Hence, our results represent the first evidence in support of a radioprotective role of ghrelin in the differentiating spermatogonia. The acutely, delicate regulation of local-produced ghrelin appears to be a fine-tune mechanism modulating the balance between testicular homeostasis and early IR injury.

The effect of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) on semen parameters in human males: a systematic review and meta-analysis.

BackgroundChronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is one of the risk factors of impaired male fertility potential. Studies have investigated the effect of CP/CPPS on several semen parameters but have shown inconsistent results. Hence, we performed a systematic literature review and meta-analysis to assess the association between CP/CPPS and basic semen parameters in adult men.MethodsSystematic literature searches were conducted with PubMed, EMBASE and the Cochrane Library up to August 2013 for case-control studies that involved the impact of CP/CPSS on semen parameters. Meta-analysis was performed with Review Manager and Stata software. Standard mean differences (SMD) of semen parameters were identified with 95% confidence intervals (95% CI) in a random effects model.ResultsTwelve studies were identified, including 999 cases of CP/CPPS and 455 controls. Our results illustrated that the sperm concentration and the percentage of progressively motile sperm and morphologically normal sperm from patients with CP/CPPS were significantly lower than controls (SMD (95% CI) −14.12 (−21.69, −6.63), −5.94 (−8.63, −3.25) and −8.26 (−11.83, −4.66), respectively). However, semen volume in the CP/CPPS group was higher than in the control group (SMD (95% CI) 0.50 (0.11, 0.89)). There was no significant effect of CP/CPPS on the total sperm count, sperm total motility, and sperm vitality.ConclusionsThe present study illustrates that there was a significant negative effect of CP/CPPS on sperm concentration, sperm progressive motility, and normal sperm morphology. Further studies with larger sample sizes are needed to better illuminate the negative impact of CP/CPPS on semen parameters.

The mammalian-specific Tex19.1 gene plays an essential role in spermatogenesis and placenta-supported development

What is the consequence of Tex19.1 gene deletion in mice? The Tex19.1 gene is important in spermatogenesis and placenta-supported development. Tex19.1 is expressed in embryonic stem (ES) cells, primordial germ cells (PGCs), placenta and adult gonads. Its invalidation in mice leads to a variable impairment in spermatogenesis and reduction of perinatal survival. We generated knock-out mice and ES cells and compared them with wild-type counterparts. The phenotype of the Tex19.1 knock-out mouse line was investigated during embryogenesis, fetal development and placentation as well as during adulthood. We used a mouse model system to generate a mutant mouse line in which the Tex19.1 gene was deleted in the germline. We performed an extensive analysis of Tex19.1-deficient ES cells and assessed their in vivo differentiation potential by generating chimeric mice after injection of the ES cells into wild-type blastocysts. For mutant animals, a morphological characterization was performed for testes and ovaries and placenta. Finally, we characterized semen parameters of mutant animals and performed real-time RT-PCR for expression levels of retrotransposons in mutant testes and ES cells. While Tex19.1 is not essential in ES cells, our study points out that it is important for spermatogenesis and for placenta-supported development. Furthermore, we observed an overexpression of the class II LTR-retrotransposon MMERVK10C in Tex19.1-deficient ES cells and testes. The Tex19.1 knock-out phenotype is variable with testis morphology ranging from severely altered (in sterile males) to almost indistinguishable compared with the control counterparts (in fertile males). This variability in the testis phenotype subsequently hampered the molecular analysis of mutant testes. Furthermore, these results were obtained in the mouse, which has a second isoform (i.e. Tex19.2), while other mammals possess only one Tex19 (e.g. in humans). The fact that one gene has a role in both placentation and spermatogenesis might open new ways of studying human pathologies that might link male fertility impairment and placenta-related pregnancy disorders. This work was supported by the Centre National de la Recherche Scientifique (CNRS), the Institut National de la Santé et de la Recherche Médicale (INSERM) (Grant Avenir), the Ministère de l'Education Nationale, de l'Enseignement Supérieur et de la Recherche, the Université de Strasbourg, the Association Française contre les Myopathies (AFM) and the Fondation pour la Recherche Médicale (FRM) and Hôpitaux Universitaires de Strasbourg.The authors have nothing to disclose.

Essential Developmental, Genomic Stability, and Tumour Suppressor Functions of the Mouse Orthologue of hSSB1/NABP2

Single-stranded DNA binding proteins (SSBs) regulate multiple DNA transactions, including replication, transcription, and repair. We recently identified SSB1 as a novel protein critical for the initiation of ATM signaling and DNA double-strand break repair by homologous recombination. Here we report that germline Ssb1−/− embryos die at birth from respiratory failure due to severe rib cage malformation and impaired alveolar development, coupled with additional skeletal defects. Unexpectedly, Ssb1 −/− fibroblasts did not exhibit defects in Atm signaling or γ-H2ax focus kinetics in response to ionizing radiation (IR), and B-cell specific deletion of Ssb1 did not affect class-switch recombination in vitro. However, conditional deletion of Ssb1 in adult mice led to increased cancer susceptibility with broad tumour spectrum, impaired male fertility with testicular degeneration, and increased radiosensitivity and IR–induced chromosome breaks in vivo. Collectively, these results demonstrate essential roles of Ssb1 in embryogenesis, spermatogenesis, and genome stability in vivo.

In Vitro Regulatory Effect of Epididymal Serpin CRES on Protease Activity of Proprotein Convertase PC4/PCSK4

PC4 or PCSK4 belongs to the 9-member superfamily of mammalian subtilases collectively called Proprotein Convertases or Proprotein Convertase Subtilisin/Kexins that convert inactive precursor proteins into their active mature forms by endoproteolytic cleavage. PC4-activity plays a crucial role in mammalian fertilization via activation of sperm surface proteins. PC4 knockout mice exhibit severely impaired male fertility due to premature sperm acrosome reaction. Regulation of sperm-PC4 activity during its storage and transport through epididymis is an important determinant for ultimate egg-binding and fertilizing capacities of sperms. Herein we show that epididymal serpin CRES (cystatin related epididymal spermatogenic) recombinant protein inhibits PC4 activity in vitro in a differential manner when measured against the fluorogenic substrate Boc- RVRR-MCA depending on its oligomeric state. Thus while CRES-dimer exhibits K(i) ∼8 μM, the corresponding monomer showed K(i) > 100 μM. Both forms also blocked PC4-mediated processing of human proIGF-2 in human placenta tropoblast cell line with dimer being more efficient. Using specific inhibitors and substrates, we also demonstrated the presence of PC4-like activity and CRES protein in varying levels in the fluids of various epididymal compartments. Our observations suggest a potential function of CRES as a regulator of PC4 in sperm-egg interaction and fertilization.

INSL5-Deficient Mice Display an Alteration in Glucose Homeostasis and an Impaired Fertility

Insulin-like factor 5 (INSL5), a member of the insulin superfamily, is expressed in the colorectum and hypothalamus. To facilitate studies into the role of INSL5, we generated Insl5(-/-) mice by gene targeting. Insl5(-/-) mice were born in the expected Mendelian ratio, reached normal body weight, but displayed impaired male and female fertility that are due to marked reduction in sperm motility and irregular length of the estrous cycle. Furthermore, Insl5(-/-) mice showed impairment in glucose homeostasis with characteristic elevation of serum glucose levels at an advanced age. Glucose and insulin tolerance tests revealed that the increased blood glucose in Insl5(-/-) mice was due to glucose intolerance resulting from reduced insulin secretion. Morphometric and immunohistological analyses revealed that the Insl5(-/-) mice had markedly reduced average islets area and β-cell numbers. Furthermore, immunohistochemistry showed the expression of INSL5 in enteroendocrine cells in the colorectal epithelium and the presence of its putative receptor relaxin family peptide receptor 4 in pancreatic islet cells. These results suggest the potential role of INSL5 signaling in the regulation of insulin secretion and β-cell homeostasis.

Protective effect of honey against cigarette smoke induced-impaired sexual behavior and fertility of male rats

Cigarette smoking is associated with sexual dysfunction and impaired fertility in males. The aim of this study was to determine the potential protective effect of honey against the toxic effect of cigarette smoke (CS) on sexual behavior and fertility of male rats. Thirty-two adult Sprague-Dawley rats were randomly divided into four groups (8 rats/group) as control, honey (H), CS and H plus CS (H + CS) groups. Rats in control and CS groups received oral administration of distilled water daily while rats in H and H + CS groups received honey (1.2 g/kg body weight/day) by oral gavage. Rats in CS and H + CS groups were also exposed to CS for 8 min 3 times/day. From 10 to 13 weeks of treatment, each male rat was cohabited with 3 untreated female rats for sexual behavioral and reproductive performance studies. Honey significantly increased the percentages of rats achieving intromission and ejaculation as well as increased mating and fertility indexes of male rats exposed to CS. Thus, honey has a protective effect against CS-induced impaired sexual behavior and fertility in male rats.

Is There a Link between Exercise and Male Factor Infertility?

The beneficial effects of physical exercise on general health are well known; however, as exercise imposes great physical stress that challenges homeostasis, it can be detrimental to certain organs/systems of the body when it is exhaustively performed. Decreased seminal parameters and sex hormone levels have been reported in male athletes and, therefore, a possible impairment of male fertility has been linked to exercise in a volume, intensity, and modality dependent-manner. Also, inherent characteristics of sportsmen (e.g. training level, adaptive capacity) may modify the response. This article aims to review the relevant literature regarding exercise and male factor infertility, while at the same time explores the possible underlying mechanisms that might be involved in this observable fact.

The role of mast cells in male infertility

Increased numbers of mast cells (MCs) were described in the testes of males exhibiting infertility many years ago. Since beneficial effects of treatment with MC blockers on impaired male fertility were reported, more attention has been drawn on the role of MCs in the male reproductive tract. The main interest is focused on testicular MCs, however MCs also occur in the epididymis and seminal fluid, which may be relevant for fertility as well. The increase in testicular MCs in close contact to the seminiferous tubules indicates a relationship between MC proliferation and a dysfunction of the blood–testis barrier. Activated MCs not only coincide with fibrotic events, but also with elevated numbers of several types of immune cells in the testes of infertile men and may, therefore, be involved in the pathogenesis of testicular inflammatory processes as well. Outside the testis, MCs have really been assigned a key role in chronic protatitis/chronic pelvic pain syndrome. The occurrence of MCs in the seminal plasma of fertile/infertile men and negative effects on sperm functions has not been clarified so far and require further investigation. Optimistic reports on the beneficial effects of the treatment with MC blockers on disturbed male fertility also warrant further confirmation.