Decreased Sperm Concentration Research Articles

Knowledge gaps in the understanding of fertility among non-medical graduate students

ObjectiveTo assess knowledge of female and male fertility among students enrolled in a Master of Business Administration (MBA) program.DesignWeb-based cross-sectional survey.SettingAcademic setting.Patient(s)Not applicable.Intervention(s)None.Main Outcome Measure(s)Knowledge of how female and male age impacts reproduction, fecundability, and success rates with in vitro fertilization (IVF).Result(s)A total of 133 female and male MBA students completed the survey. Nearly 10% of participants were not aware that women are born with a fixed number of oocytes and that oocyte quantity and quality decline with age. More than 30% of participants overestimated fecundability in women aged ≥35 years, and >50% overestimated IVF success rates in women older than 40 years. Fifteen percent of participants did not know that men have stem cells in the testes, and >25% were not aware that men experience a decrease in sperm concentration and quality with age. Nearly 30% believed that a man’s age never impacts reproductive outcomes. Less than 30% of participants correctly estimated fecundability and IVF success rates based on male age.Conclusion(s)These data highlight important knowledge gaps in a highly educated group of MBA students, most whom desire future childbearing. Specifically, there is a lack of understanding of both male and female reproductive aging and an overestimation of treatment success. As delayed childbearing continues, particularly among those with high educational attainment, attention should be focused on introducing broad fertility education at a younger age to improve future reproductive success.

Myeloperoxidase and lactoferrin expression in semen fluid: Novel markers of male infertility risk?

Research QuestionInfections and/or inflammation processes of male genital tract are highly prevalent and often associated with risk of infertility. These conditions represent a possible cause of leukocytospermia, which is still under debate. Leukocytes are key-factors to reactive oxygen species (ROS) production and the increase of ROS in semen fluid is associated with the worsening of semen parameters. At present, there are not appropriate andrological tests to identify asymptomatic inflammatory conditions when the amount of leukocytes is in the normal range. DesignWe studied the innate immunity profile of myeloperoxidase and lactoferrin (MPO/LAC) proteins expressed in the semen fluid of 39 men evaluated for couple infertility, in the absence of leukocytospermia. ResultsThe presence of both MPO and LAC proteins was associated with a decrease of sperm concentration and of progressive/total motility, whereas the increase of MPO-/LAC + indicated a worse sperm morphology. It is worth to report the predictive potential of MPO+/LAC + pattern (above 4.36 %) as a biological marker to distinguish normozoospermic from pathological patients. ConclusionOur findings indicate MPO/LAC analysis as a potential diagnostic tool to identify asymptomatic conditions eventually related to male infertility, even when the number of leukocytes in semen fluid is below 1 million/mL.

Verapamil‐induced ion channel and miRNA expression changes in rat testis and/or spermatozoa may be associated with male infertility

The effect of verapamil, a calcium channel blocker, on male fertility in terms of ion channel and miRNA gene expressions in testis/spermatozoa was evaluated in this study. Rats were divided into sham and verapamil groups (n=15). Verapamil was performed orally for 60days. Sperm parameters and levels of serum follicle-stimulating hormone (FSH), luteinising hormone (LH) and testosterone (T) hormones were analysed. Alterations of microRNA (miRNA) and ion channel gene expressions in spermatozoa/testis were detected by using qPCR. Verapamil treatment reduced sperm concentration. Increased serum FSH, LH and T hormone levels were detected. Upregulated transient receptor potential cation channel subfamily V member 5 (TRPV5) and potassium voltage-gated channel subfamily J member 11 (KCNJ11) gene expressions and downregulated miR-let-7b, miR-10a, miR-320 and miR-760 expressions were found in testis of verapamil group. However, upregulated anoctamin 1 (ANO1), ATP-binding cassette subfamily C member 9 (ABCC9), miR-27a and miR-130a expressions and downregulated miR-20a, miR-92a, miR-132, miR-320 and miR-760 expressions were detected in spermatozoa. In addition, these altered gene expressions were found to be associated with decreased sperm concentration. The results indicate that the changes in testicular and/or spermatozoal ion channels and miRNA expressions due to verapamil treatment may affect male fertility.

Impact of timing of the anorexigen sibutramine administration on reproductive end-points of male rats.

Sibutramine is a non-selective serotonin-norepinephrine reuptake inhibitor orally administered for weight loss. In a previous study, we showed pharmacological mechanisms involved in the reduction of sperm quality and fertility of rats exposed for 30days to this anorexigen in the light phase of the light-dark (l/d) cycle. It is already known that rodents are nightlife animals, with higher metabolic activity during the dark phase than in the light phase of the light-dark (l/d) cycle. Thus, the present study aimed to investigate whether the deleterious effects on reproductive parameters after sibutramine administration would be enhanced after a shorter period of exposure during the dark phase of the l/d cycle. For this, adult male Wistar rats were treated with sibutramine (10mg/kg/d) or vehicle for 15days during the dark phase of the l/d cycle. Sibutramine treatment decreased final body and reproductive organ weights, as well as serum testosterone levels. Sperm transit time through the epididymis was accelerated, and sperm concentration and motility were diminished in the sibutramine-exposed rats. The decrease in sperm concentration was also verified in the epididymal histological sections. In conclusion, the deleterious effects of sibutramine on reproductive parameters of male rats were enhanced when the exposure occurred in the dark phase of the l/d cycle, even after a short exposure duration. Our results reinforce the impact of timing on drug therapeutic action.

The effect of cigarette smoking on the semen parameters of infertile men

Introduction 36.9% of men worldwide use tobacco. Previous studies suggest a negative effect of cigarette smoking on semen quality, but the results are contradictory. We have studied the effects of smoking on the semen characteristics such as sperm concentration, semen volume, sperm motility, sperm vitality and sperm morphology in a large group of infertile men. Methods This retrospective study was conducted on a total of 5146 infertile men with at least one year of idiopathic infertility, who admitted to the Centre for Reproductive medicine (CRG) at the Brussels University Hospital, Belgium between 2010 and 2017. The smokers were classified as mild (1-10 cigarettes/d), moderate (11-20 cigarettes/d) or heavy smokers (> 20 cigarettes/d). Semen analysis was performed for all patients. Statistical analysis was performed using the R software package and t-test or Mann-Whitney U tests were used, group comparisons were performed using ANOVA, ANCOVA or Kruskal-Wallis tests as appropriate. A p-value <0.05 was considered as statistically significant. Results Comparing the semen parameters in the two global groups showed that smoking had a significant decrease in semen volume (p=0.04074) and sperm concentration (p=0.029). ANOVA testing on the different smoking groups versus non-smoking group showed a significant decrease in sperm concentration (p=0.0364). After adjusting for the confounders, age and testosterone, ANCOVA testing showed significant effect on the sperm concentration (p=0.03871) in smokers versus non-smokers. No significant correlation was detected between the other semen characteristics. Conclusion We concluded that smoking had a significant and independent effect on the sperm concentration in a semen analysis. Other parameters, like semen volume, sperm motility, sperm vitality and sperm morphology were not influenced by smoking.

Gestational and pubertal exposure to low dose of di-(2-ethylhexyl) phthalate impairs sperm quality in adult mice

Di-(2-ethylhexyl)-phthalate (DEHP) is a compound widely used as a plasticizer, which can leach from plastics into the environment and thus influence human health. The aim of this study was to analyze whether exposure to an environmentally relevant dose of DEHP during mice fetal development or puberty can cause long-lasting changes detectable month/s after the last exposure. We used a DEHP concentration relevant to a daily human intake of 2.4–3 μg/kg of body weight/day. CD1 outbred mice were treated either in utero or postnatally during puberty and analyzed in adulthood. Analyzing fertility parameters using morphometric, histologic, genomic and proteomic methods we showed that DEHP exposure leads to decreased sperm concentration and quality, in both experimental groups. Moreover, the changes in anogenital distance, seminal vesicle weight, and testicular gene expression suggest a disturbance of androgen signaling in exposed animals. In conclusion, we hereby present, that the prenatal and pubertal exposure to a low dose of DEHP negatively influenced reproductive endpoints in male mice, and some of the effects were persistent until adulthood.

The protective effect of Fumaria officinalis against the testicular toxicity of fluoxetine in rat

Background and objective: Extracts of Fumaria species have been traditionally used for the treatment of some skin diseases, rheumatism, stomach ache, fever, and male infertility mainly because of the presence of isoquinoline alkaloids. On the other side, fluoxetine is used as an antidepressant induce sexual dysfunction and a decrease in sperm concentration, motility, and morphology. The present investigation dealt with the study of the protective role played by the Fumaria officinalis extract against the selective serotonin reuptake inhibitor (SSRI) induced testicular toxicity in the rat. Therefore, the purpose of this work was to determine the benefits of Fumaria officinalis extract in animals treated with fluoxetine. Methods: Thirty six male rats were divided into three following groups, control group, fluoxetine (20 mg/kg/day) treated-group, and the same dose of Fluoxetine plus Fumaria officinalis extract (150 mg/kg/day) as a third group. Drugs and extract were administered orally for 30 days. Sections of testes were stained by Haematoxylin and Eosin. Results: Fluoxetine has caused several structural changes in the rat testis such as vacuolation within germinal epithelium of seminiferous tubules, decrease the diameter of these tubules and decrease number of sertoli and germinal cells. Treating the fluoxetine exposed rats with Fumaria officinalis extract has shown to ameliorate the above histological changes. Conclusion: Fumaria officinalis extract can protect testis from histological alterations caused by the toxicity of the fluoxetine.

Inhibition of ferroptosis attenuates busulfan-induced oligospermia in mice

Busulfan is commonly used for cancer chemotherapy, nevertheless it cause male infertility via damaging the germ cells. Therefore, the underlying mechanism should be explored. In the present study, we demonstrated for the first time that ferroptosis was involved in busulfan-induced oligospermia in mice. Mice were given testicular injection of busulfan on both sides at the dose of 4 mg/kg body weight to establish the model of oligospermia. Four weeks later, the results showed that busulfan-treated mice exhibited decreased sperm concentration and motility, along with features of typical ferroptosis in testis, such as increased malondialdehyde (MDA) content and prostaglandin-endoperoxide synthase (PTGS2) mRNA expression, and decreased NADPH content. Inhibition of ferroptosis by ferrostatin-1 (Fer-1) or deferoxamine (DFO) partially alleviated busulfan-induced oligospermia in mice. Additionally, we also revealed that busulfan treatment induced spermatogenic cells ferroptosis by down-regulating nuclear factor-E2-related factor 2 (Nrf2) and glutathione peroxidase 4 (GPX4) expressions, and decreasing iron efflux through reduction of ferroportin 1 (FPN1) expression. Fer-1 or DFO obviously reversed busulfan-induced ferroptosis by increasing Nrf2, GPX4 and FPN1 expressions. Furthermore, after activation of Nrf2 by sulforaphane, sperm concentration and motility in busulfan-treated mice increased, accompanied by enhanced expressions of GPX4 and FPN1. These findings imply that busulfan-induced ferroptosis might be mediated via inhibition of Nrf2-GPX4 (FPN1) signaling pathway, and highlight that targeting ferroptosis serves as a potential strategy for prevention of busulfan-induced damage and male infertility.

Prior and novel coronaviruses, Coronavirus Disease 2019 (COVID-19), and human reproduction: what is known?

ObjectiveTo summarize current understanding of the effects of novel and prior coronaviruses on human reproduction, specifically male and female gametes, and in pregnancy.DesignReview of English publications in PubMed and Embase to April 6, 2020.Method(s)Articles were screened for reports including coronavirus, reproduction, pathophysiology, and pregnancy.Intervention(s)None.Main Outcome Measure(s)Reproductive outcomes, effects on gametes, pregnancy outcomes, and neonatal complications.Result(s)Seventy-nine reports formed the basis of the review. Coronavirus binding to cells involves the S1 domain of the spike protein to receptors present in reproductive tissues, including angiotensin-converting enzyme-2 (ACE2), CD26, Ezrin, and cyclophilins. Severe Acute Respiratory Syndrome Coronavirus 1 (SARS–CoV-1) may cause severe orchitis leading to germ cell destruction in males. Reports indicate decreased sperm concentration and motility for 72–90 days following Coronavirus Disease 2019 (COVID-19) infection. Gonadotropin-dependent expression of ACE2 was found in human ovaries, but it is unclear whether SARS–Coronavirus 2 (CoV-2) adversely affects female gametogenesis. Evidence suggests that COVID-19 infection has a lower maternal case fatality rate than SARS or Middle East respiratory syndrome (MERS), but anecdotal reports suggest that infected, asymptomatic women may develop respiratory symptoms postpartum. Coronavirus Disease 2019 infections in pregnancy are associated with preterm delivery. Postpartum neonatal transmission from mother to child has been reported.Conclusion(s)Coronavirus Disease 2019 infection may affect adversely some pregnant women and their offspring. Additional studies are needed to assess effects of SARS–CoV-2 infection on male and female fertility.

Could leptin be responsible for the reproductive dysfunction in obese men?

Low sperm concentration, increased fraction of morphologically abnormal sperm, and raised levels of markers of oxidative stress are often reported in the seminal plasma of infertile obese males. The precise reason for changes remains unknown. This short review summarises evidence from human and animal studies linking leptin to the reproductive dysfunction reported in obese males and presents a possible mechanism for this based on the available data in the literature. Serum leptin concentrations correlate positively with body fat mass but its precise link to semen abnormalities reported in obese males has yet to be conclusively established. Decreased sperm concentration, increased fraction of morphologically abnormal sperm and increased markers of oxidative stress have been reported following six weeks of daily leptin treatment to normal weight rats. In addition, decreased expression of endogenous antioxidant enzymes and increased expression of respiratory chain enzymes noted in the testes of leptin treated rats increases the propensity to oxidative stress. Besides that, leptin’s interference with histone to protamine transition in the DNA of sperm increases the susceptibility of sperm to free radical attack and may explain the often reported higher DNA fragmentation index in sperm of obese males. Concurrent supplementation of melatonin, a natural anti-oxidant, to these rats prevents the effects of leptin. The role of leptin in obesity-related reproductive dysfunction has to be considered seriously and these effects of leptin might involve increased oxidative stress.

Характеристика жизнеспособности сперматозоидов у потомства самок крыс с экспериментальным сахарным диабетом 1 типа при действии иммобилизационного стресса

One of the main factors underlying the development of prenatal stress is maternal type 1 diabetes. Its influence on the formation of the male reproductive system of the offspring has not been well studied. Therefore, this study was aimed at the analysis of the spermatozoa motor activity characteristics in mature offspring of the mothers with experimental type 1 diabetes mellitus, subjected to the immobilization stress. The study was performed on white laboratory Wistar rats (females), in which the type 1 diabetes mellitus was inducted, and their mature offspring. Spermatozoa were obtained from the epididymis; their motility was taken into account when determining their content in a unit volume. In order to study the antistress resistance of sperm, the the experimental animals were subjected to a model of immobilization stress. We demonstrate that the sperm concentration is decreased in the offspring of female rats with experimental diabetes. This decrease also occurs in animals subjected to the immobilization stress, in both intact and experimental groups. The fertile to non-fertile germ cells ratio is also affected by the immobilization stress. We show that the number of Leydig cells and their activity index were reduced in experimental animals. Based on these results, we conclude that the fertility and antistress resistance of spermatogenesis are reduced in the offspring of the female rats with experimental diabetes mellitus. The hypothalamic-pituitary-gonadal system provides control of the reproductive system, primarily through testosterone, which is produced by the Leydig cells and is involved in the regulation of the spermatogenesis. The activation of the hypothalamic-pituitary-adrenal system under hypoglycemia leads to the suppression of the hypothalamic–pituitary–gonadal system activity. We propose that the immobilization stress raises the corticosteroid levels, which further inhibits the secretory activity of the Leydig cells, leading to the disruption of the spermatogenesis and the decrease in sperm concentration and motor activity.

The Impact of Zika Virus Infection On Human Semen: A Case Study

The outbreak of Zika virus (ZIKV) in Brazil and in many countries was marked by the occurrences of fetal malformations and neurological effects upon infection of pregnant women. Like other members of the Flaviviridae family, ZIKV in semen is infectious and sexually transmitted. Viral persistence in the male genital tract is unresolved and still needs further understanding. A regular semen donor was followed from the acute phase of ZIKV infection, up to 8 months after ZIKV in his body fluids became undetected. Immunofluorescence assay was performed in semen samples before and after the infection. A significant decrease in sperm concentration and in the percentage of progressive motility of sperm was observed. The methodology adopted for clearance of sexually transmitted viruses decreased virus load, but the complete clearance of ZIKV from semen was not achieved.

The impact of selected modifiable lifestyle factors on male fertility in the modern world.

IntroductionThe modern man during his reproductive period is exposed to the negative influence of widespread lifestyle-related habits. The available studies show a significant decline in the quality of young men's sperm, which results in male and female infertility factors being given equal consideration. The progressive decline of sperm quality has lowered the spermiogram parameters proposed by the World Health Organization.Material and methodsWe performed a review of the literature on the most common unhealthy habits in the modern world, such as obesity, mobile phone usage, smoking and alcohol intake, and their reported effects on male fertility. Several papers including original, review and meta-analysis were searched using the ScienceDirect and Web of Science databases.ResultsAll the factors under analysis contribute to a significant deterioration of sperm quality, mainly through decreased sperm concentration, vitality, motility and morphology.ConclusionsLifestyle-related factors are a significant cause of male infertility in the world today. Studies have shown that sperm quality is essentially determined by: obesity, nicotine addiction, heavy exposure to electromagnetic compatibility radiation-emitting devices and alcohol consumption. Weight loss and cessation or limitation of unhealthy lifestyle-related factors might represent the best course of action for any couple trying to achieve pregnancy.

Effect of feeding male mice with palm, fish, and sunflower oils on sperm characteristics and sex ratio of offspring.

Several studies have indicated that feeding female animal with fatty acids could result in alteration of offspring sex ratio; however, there is little information available regarding the effect of feeding male animal with fatty acids on sex ratio of offspring. The aim of current study was to investigate the effect of paternal feeding with n-3 and n-6 polyunsaturated fatty acids (PUFAs) on sperm characteristics and sex ratio of offspring in mice. Male mice received 2.50% of palm oil (control), fish oil (n-3 PUFAs) or sunflower oil (n-6 PUFAs) for two months. Sperm kinematics and viability were assessed using computer-assisted sperm analyzer and eosin-Y staining, respectively. Additionally, female mice were randomly introduced to males of three experimental groups to determine reproductive parameters including litter size, conception rate and sex ratio. Fish oil enhanced sperm concentration, motility and viability, whereas sunflower oil decreased sperm concentration. Nevertheless, progressive motility, velocity, linearity and straightness of sperms were not affected by source of fatty acids. Although supplementation with fish oil resulted in male-biased sex ratio, palm and sunflower oils did not impact sex ratio. Besides, source of fatty acids failed to influence conception rate and litter size. In conclusion, the present study provided evidence for the impact of paternal fish oil consumption on sex ratio of offspring for the first time. Moreover, it showed beneficial effect of n-3 PUFAs and adverse effects of n-6 PUFAs on seminal parameters.

Association between ambient temperature and semen quality: A longitudinal study of 10 802 men in China

Semen quality is a vital determinant for male fertility. The process of spermatogenesis is highly sensitive to fluctuations in temperature. However, the impact of ambient temperature on semen quality remains unclear. We aimed to quantitatively assess the association between ambient temperature and semen quality. Using data from Hubei provincial human sperm bank in Wuhan, China, we conducted a longitudinal study including 10 802 volunteers who lived in Wuhan and passed the initial physical examination for sperm donation between Mar 27, 2013 and April 9, 2018. Semen quality parameters including sperm concentration, total sperm number, total motility, progressive motility, total motile sperm count and progressively motile sperm count were determined in the sperm bank. We used linear mixed models to identify estimate changes of outcomes in relation to ambient temperature (i.e., air temperature and apparent temperature) exposure measured as the mean daily temperature during the 0–90 days before semen collection. Among 10 802 subjects who underwent 41 689 semen examinations, we observed inverted U-shaped exposure-response associations between air temperature exposure and all semen quality parameters, with an identical threshold exposure of 13 °C. For air temperature exposure <13 °C, each 5 °C lower temperature was significantly associated with 1.94 × 106/ml, 7.12 × 106, 0.77%, 0.81%, 6.48 × 106, and 5.87 × 106 decrease in sperm concentration, total sperm count, total motility, progressive motility, total motile sperm count and progressively motile sperm count, respectively. When air temperature exposure was ≥13 °C, each 5 °C higher temperature was significantly associated with 0.70 × 106/ml, 4.09 × 106, 1.01%, 1.06%, 4.31 × 106, and 4.20 × 106 decrease in sperm concentration, total sperm count, total motility, progressive motility, total motile sperm count and progressively motile sperm count, respectively. Age, BMI and smoking did not significantly modify these associations. Similar results were observed for apparent temperature. This study provides a comprehensive picture of nonlinear association between ambient temperature and semen quality, as well as an optimal temperature for the benefit of semen quality. Both lower and higher ambient temperature exposures compared with the optimal temperature were significantly associated with decreased semen quality. The findings highlight the needs and importance to reduce extreme ambient temperature exposures in maintaining optimal semen quality for men. Further investigation is warranted to determine the causality of the association and the underlying mechanisms.

Concentrated ambient PM2.5exposure affects mice sperm quality and testosterone biosynthesis

BackgroundStudies suggested that PM2.5 exposure could lead to adverse reproductive effects on male animals. However, the underlying mechanism is still not clear. Besides, animals in the majority of previous studies were exposed to PM2.5 through intratracheal instillation which should be improved. In addition, limited amount of research has been conducted in China where the PM2.5 concentration is higher and the PM2.5 components are different. The aim of this work is to explore the effects of concentrated ambient PM2.5 (CAP) on mice sperm quality and testosterone biosynthesis.MethodsA total of 12 male C57BL/6 mice were exposed to filtered air (FA) or CAP for 125 days using the Shanghai Meteorological and Environmental Animal Exposure System. The mice sperm concentration, sperm motility, DNA fragmentation index, high DNA stainability and plasma testosterone were analyzed. Testicular histology and sperm morphology were observed through optical microscope. Testosterone biosynthesis related gene expressions were analyzed using real-time PCR, including cytochrome P450 CHOL side-chain cleavage enzyme (P450scc), steroidogenic acute regulatory protein (StAR), 3β-hydroxysteroid dehydrogenase (3β HSD), 17β-hydroxysteroid dehydrogenase, cytochrome P450 aromatase (P450arom), estrogen receptor (ER), androgen receptor (AR) and follicle stimulating hormone receptor (FSHR).ResultsExposure to CAP resulted in disturbance of various stages of spermatogenesis and significant higher percentage of abnormal sperm (FA vs. CAP: 24.37% vs. 44.83%) in mice testis. CAP exposure significantly decreased sperm concentration (43.00 × 106 vs. 25.33 × 106) and motility (PR: 63.58% vs. 55.15%; PR + NP: 84.00% vs. 77.08%) in epididymis. Plasma testosterone concentration were significantly declined (0.28 ng/ml vs. 0.69 ng/ml) under CAP exposure. Notably, the levels of testosterone biosynthesis related genes, StAR, P450scc, P450arom, ER and FSHR were significantly decreased with CAP exposure.ConclusionConcentrated ambient PM2.5 exposure altered mice sperm concentration, motility and morphology, which might be mediated primarily by the decline in testosterone concentration and testosterone biosynthesis process.

Modulatory effects of ghrelin on sperm quality alterations induced by a fructose-enriched diet

The objectives of this study were: 1) to evaluate the effects of a fructose enriched diet (FED) on rat sperm quality, epididymal function (i.e. oxidative stress and alpha-glucosidase expression) and testosterone concentrations; 2) to determine if the administration of ghrelin (Ghrl), reverses the effects induced by FED.After validating the protocol as an inductor of metabolic syndrome like-symptoms, adult male rats were assigned to one of the following treatments for 8 weeks: FED = 10% fructose enriched in water (v/v); FED + Ghrl = fructose enriched diet plus Ghrl (6 nmol/animal/day, s.c.) from week 6–8; or C = water without fructose (n = 5–10 animals/group).FED significantly decreased sperm concentration and motile sperm count/ml vs C (FED: 19.0 ± 1.6 × 106sperm/ml and 834.6 ± 137.0, respectively vs C: 25.8 ± 2.8 × 106 and 1300.4 ± 202.4, respectively; p < 0.05); ghrelin injection reversed this negative effect (23.5 ± 1.6 × 106sperm/ml and 1381.7 ± 71.3 respectively). FED resulted in hypogonadism, but Ghrl could not normalize testosterone concentrations (C: 1.4 ± 0.1 ng/ml vs FED: 0.8 ± 0.2 ng/ml and FED + Ghrl: 0.6 ± 0.2 ng/ml; p < 0.05). Ghrelin did not reverse metabolic abnormalities secondary to FED. FED did not alter epididymal expression of antioxidants enzymes (superoxido-dismutase, catalase and glutathione peroxidases –Gpx-). Nevertheless, FED + Ghrl significantly increased the expression of Gpx3 (FED + Ghrl: 3.47 ± 0.48 vs FED: 0.69 ± 0.28 and C: 1.00 ± 0.14; p < 0.05). The expression of neutral alpha-glucosidase, which is a marker of epididymal function, did not differ between treatments.In conclusion, the administration of Ghrl modulated the negative effects of FED on sperm quality, possibly by an epididymal increase in Gpx3 expression. However, Ghrl could not neither normalize the metabolism of FED animals, nor reverse hypogonadism.

Effects of synthetic (JWH-018) cannabinoids treatment on spermatogenesis and sperm function

JWH-018 is a synthetic cannabinoid which has been increasingly used by adolescents and adults, and is known to cause severe multi-organ failure. However, little is known about the complications and toxicological effects of JWH-018 on reproduction system. Therefore, the aim of the present study is to investigate the effects of JWH-018 on testis and spermatogenesis. Thirty CD-1 male rats were distributed into six groups, control group (C1 and C2), ethanol group (E1 and E2), and JWH-018 group (JWH1 and JWH2), which were administered 0.9% NaCl, %100 ethanol, and JWH-018 (0.3 mg/kg) respectively for 9 d. We euthanized C1, E1, and JWH1 group mice at day 2 and C2, E2, and JWH2 group mice at 45 d after the last injection to evaluate the acute testis damage and potential recovery of spermatogenesis. The histopathology of seminiferous epithelium was evaluated and organ weight, sperm concentration and motility, membrane integrity, and serum testosterone levels were statistically analyzed. In JWH1, seminiferous tubule degeneration, partial germ cell depletion disorganized seminiferous epitheliums were seen. We also observed significantly decreased sperm concentration, sperm motility, intact membrane, and testosterone levels in JWH1 group compared to other groups. Forty-five days after the JWH-018 treatment, sperm concentration, motility, and testosterone level were increased, suggesting that testis and spermatogenesis can recover. We concluded that the use of JWH-018 may adversely affect male reproductive potential and testis histopathology.

Mediation of association between polycyclic aromatic hydrocarbon exposure and semen quality by spermatogenesis-related microRNAs: A pilot study in an infertility clinic

Spermatogenesis-related microRNAs (miRNAs) are vulnerable to polycyclic aromatic hydrocarbons (PAHs). Changes in spermatogenesis-related miRNAs may be biological intermedia in mechanisms linking PAHs and semen quality. This study aimed to investigate whether spermatogenesis-related microRNAs mediate the associations between PAHs and semen quality. We measured 10 monohydroxylated PAHs (OH-PAHs) in repeated urine samples and three candidate spermatogenesis-related miRNAs (miRNA106a, miRNA21, and miRNA34c) in seminal plasma from men attending an infertility clinic (n = 111). Mediation analysis was applied to determine the mediating role of spermatogenesis-related miRNAs in the association of PAH exposure with semen quality. Urinary 2-OHFlu and 2-OHPh were related to reduced seminal plasma miRNA34c (p for trend = 0.05 and 0.03, respectively). Urinary 9-OHPh was related to reduced seminal plasma miR106a (p for trend = 0.02), which in turn, was positively associated with sperm concentration, sperm count, sperm total motility, and progressive motility (all p for trends<0.05). Up to 43.8% of the eff ;ect of urinary 9-OHPh on decreased sperm concentration was mediated by seminal plasma miR106a. Our results suggested that certain PAH exposure was associated with reduced spermatogenesis-related miRNAs and such alterations might be an intermediate mechanism by which PAHs exert its adverse effects on semen quality.

556P - Sex hormones and sperm parameters after adjuvant oxaliplatin-based treatment for colorectal cancer

BackgroundThe occurrence of colorectal cancer in individuals with potentially reproductive age has increased. Oxaliplatin is a cornerstone treatment in the adjuvant setting for stage III and high-risk stage II colorectal cancer in patients up to 70 years of age. The aim of this study was to investigate sex hormones and sperm function after oxaliplatin-based chemotherapy to clarify the risk for hypogonadism and infertility. MethodsThrough 2006-2013 20 males (aged ≤55 and younger) and 16 females (aged ≤40 and younger) were included. All had undergone radical surgery due to colorectal cancer, and were planned for adjuvant oxaliplatin in combination with 5-fluorouracil. Measurement of LH, FSH, testosterone, SHBG and sperm analysis was done in males. LH, FSH and estradiol was measured in females. Measurements were done after surgery, after cessation of adjuvant cytostatic treatment and at follow-up 1-5 years after end of treatment. ResultsFSH and testosterone levels increased in males, but were restored at follow-up. No patients went from normal gonadal function to hypogonadism. There was a tendency towards a decrease in sperm concentration, (p=0.,063). When comparing sperm concentration and rapid progressive motility before treatment and at follow-up, there was no differences, and we observed no patients that turned overtly infertile by treatment. No distinct altering of gonadal function could be observed in the females. ConclusionsFrom the results of this study, oxaliplatin seems to incur transient decrease in sperm concentration with recovery, and some but not pronounced increase in FSH in males. The risk for infertility and hypogonadism in males and females after adjuvant oxaliplatin-based chemotherapy seems to be low to moderate, but the general recommendation of appropriate fertility conserving measures shall should not be changed. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureP. Österlund: Honoraria (self): Amgen; Honoraria (self): Bayer; Honoraria (self): Celgene; Honoraria (self): Eli Lilly; Honoraria (self): Merck; Honoraria (self): Nordic Drugs; Honoraria (self): Roche; Honoraria (self): Sanofi; Honoraria (self): Servier; Travel / Accommodation / Expenses: Pierre Fabre; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: AbbVie. E. Hofsli: Honoraria (self): Amgen. H. Sorbye: Honoraria (self): Novartis; Honoraria (self): Ipsen; Honoraria (self): Pfizer; Honoraria (self): Keocyt; Honoraria (self): AstraZeneca; Honoraria (self): Roche; Honoraria (self): Amgen; Honoraria (self): Merck; Honoraria (self): Shire; Honoraria (self): Celgene; Honoraria (self): Nordic Drugs. All other authors have declared no conflicts of interest.