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Concept: Semen

503

Adverse temporal trends in human semen quality and cryptorchidism in infants have been associated with exposure to environmental chemicals (ECs) during development. Here we report that a population of breeding dogs exhibit a 26 year (1988-2014) decline in sperm quality and a concurrent increased incidence of cryptorchidism in male offspring (1995-2014). A decline in the number of males born relative to the number of females was also observed. ECs, including diethylhexyl phthalate (DEHP) and polychlorinated bisphenol 153 (PCB153), were detected in adult dog testes and commercial dog foods at concentrations reported to perturb reproductive function in other species. Testicular concentrations of DEHP and PCB153 perturbed sperm viability, motility and DNA integrity in vitro but did not affect LH stimulated testosterone secretion from adult testis explants. The direct effects of chemicals on sperm may therefore contribute to the decline in canine semen quality that parallels that reported in the human.

Concepts: Male, Reproduction, Sperm, Sex, Testicle, Spermatozoon, Semen, Epididymis

321

In December 2013, during a Zika virus (ZIKV) outbreak in French Polynesia, a patient in Tahiti sought treatment for hematospermia, and ZIKV was isolated from his semen. ZIKV transmission by sexual intercourse has been previously suspected. This observation supports the possibility that ZIKV could be transmitted sexually.

Concepts: HIV, AIDS, Sexual intercourse, Semen, Sexually transmitted disease, Human sexual behavior, Pacific Ocean, French Polynesia

167

OBJECTIVE: To investigate the efficacy of DA-8031, a novel compound for the treatment of premature ejaculation (PE), we performed in vivo pharmacological studies using 2 preclinical animal models, electrical stimulation of sensory branch of pudendal nerve (SBPdn) and para-chloroamphetamine (PCA)-induced ejaculation model. METHODS: First of all, in electrical stimulation of an SBPdn model, an SBPdn in the pelvic canal of the spinal cord transected from rats was identified. Then an electromyogram (EMG) of the bulbospongiosus (BS) muscle was recorded during electrical stimulation of SBPdn after single intravenous (IV) dosing of DA-8031 and its reference drug, dapoxetine. In the second model, both seminal vesicle pressure (SVP) and the EMG profile of the BS muscle were recorded in PCA-induced ejaculation animals after treated with the same dosing regimen. RESULTS: Area under the curve (AUC) of the BS muscle by EMG wave exhibited a significant reduction in the DA-8031 and dapoxetine 3 mg/kg treated groups, and maximum amplitudes were also significantly decreased in DA-8031 1, 3 mg/kg and dapoxetine 3 mg/kg dose level in the SBPdN stimulation model. Consistent with these findings, in a PCA-induced ejaculation model, SVP increase was significantly inhibited from DA-8031 0.3 mg/kg dose level, and AUC of BS muscle EMG significantly decreased in the DA-8031 1, 3 mg/kg groups. CONCLUSION: The present study implied that DA-8031 contributed to an effective co-coordinated inhibition of the expulsion phase of ejaculation by modulating BS muscle activity and the emission phase through blocking SVP rise. From these findings, DA-8031 is further expected to have clinical efficacy in human studies.

Concepts: Semen, Electromyography, Orgasm, Ejaculation, Penis, Premature ejaculation, Pudendal nerve, Bulbospongiosus muscle

167

OBJECTIVE: To determine the diagnostic value of the following sperm function tests in predicting the fertilizing ability of spermatozoa in conventional in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI): hyaluronan-binding assay (HBA), DNA fragmentation (Halosperm), and hyperactivity. DESIGN: Prospective study. SETTING: University medical center. PATIENT(S): 133 couples undergoing infertility treatment with IVF/ICSI. INTERVENTION(S): Analysis of sperm DNA fragmentation, hyaluronan-binding ability, and hyperactivation on washed semen samples used for the insemination of oocytes. MAIN OUTCOME MEASURE(S): Correlation between the results of sperm function tests and the fertilization rate (FR) or embryo quality (EQ) after IVF and ICSI. Comparison of the sperm DNA fragmentation, hyperactivation, and hyaluronan binding ability between cycles with less than 50% (group 1) and more than 50% (group 2) of oocytes fertilized after IVF. RESULT(S): Both FR and EQ in IVF cycles negatively correlated with sperm DNA fragmentation. Furthermore, a positive correlation was observed between FR and hyaluronan-binding ability or induced hyperactivity. The semen samples from the IVF cycles with low FR (group 1) were characterized by statistically significantly higher sperm DNA fragmentation and lower hyaluronan-binding ability in comparison with semen samples from the group with high levels of fertilization (group 2). In ICSI cycles, no relationship was found between sperm function tests and FR or EQ. CONCLUSION(S): The Halosperm test, the HBA test, and induced hyperactivity are useful in predicting the ability of spermatozoa to fertilize oocytes in IVF and are helpful in distinguishing semen samples suitable for IVF or ICSI.

Concepts: Reproduction, Sperm, Fertility, Spermatozoon, In vitro fertilisation, Semen, Implantation, Fertilisation

140

Anurans show the highest diversity in reproductive modes of all vertebrate taxa, with a variety of associated breeding behaviours. One striking feature of anuran reproduction is amplexus. During this process, in which the male clasps the female, both individuals' cloacae are juxtaposed to ensure successful external fertilization. Several types of amplexus have evolved with the diversification of anurans, and secondary loss of amplexus has been reported in a few distantly related taxa. Within Nyctibatrachus, a genus endemic to the Western Ghats of India, normal axillary amplexus, a complete loss of amplexus, and intermediate forms of amplexus have all been suggested to occur, but many species remain unstudied. Here, we describe the reproductive behaviour of N. humayuni, including a new type of amplexus. The dorsal straddle, here defined as a loose form of contact in which the male sits on the dorsum of the female prior to oviposition but without clasping her, is previously unreported for anurans. When compared to known amplexus types, it most closely resembles the form of amplexus observed in Mantellinae. Furthermore, we prove that, opposed to the situation in most anurans, male semen release happens before egg deposition. We hypothesize that the male ejaculates on the female’s dorsum and that sperm subsequently runs from her back and hind legs before fertilizing the eggs. A second feature characterizing anuran breeding is the advertisement call, mostly produced solely by males. Despite recent descriptions of several new Nyctibatrachus species, few studies have explored their vocal repertoire. We describe both the male advertisement call and a female call for N. humayuni. The presence of a female call has not been reported within Nyctibatrachidae, and has been reported in less than 0.5% of anuran species. Altogether, our results highlight a striking diversity and several unique aspects of Nyctibatrachus breeding behaviour.

Concepts: Human, Male, Reproduction, Female, Sperm, Spermatozoon, Semen, Hermaphrodite

83

A total of 1,215 young Danish men aged 18-28 years were recruited between 2008 and 2012 when they attended a compulsory medical examination to determine their fitness for military service. The participants delivered a semen sample, had a blood sample drawn, and underwent a physical examination. They responded to questionnaires including information on marijuana and recreational drug use during the past 3 months (no use, use once per week or less, or use more than once per week). A total of 45% had smoked marijuana within the last 3 months. Regular marijuana smoking more than once per week was associated with a 28% (95% confidence interval (CI): -48, -1) lower sperm concentration and a 29% (95% CI: -46, -1) lower total sperm count after adjustment for confounders. The combined use of marijuana more than once per week and other recreational drugs reduced the sperm concentration by 52% (95% CI: -68, -27) and total sperm count by 55% (95% CI: -71, -31). Marijuana smokers had higher levels of testosterone within the same range as cigarette smokers. Our findings are of public interest as marijuana use is common and may be contributing to recent reports of poor semen quality.

Concepts: Drug, Semen analysis, Opioid, Semen, Cannabis, Psychoactive drug, Recreational drug use, Prohibition

73

Male infertility affects up to 12% of the world’s male population and is linked to various environmental and medical conditions. Manual microscope-based testing and computer-assisted semen analysis (CASA) are the current standard methods to diagnose male infertility; however, these methods are labor-intensive, expensive, and laboratory-based. Cultural and socially dominated stigma against male infertility testing hinders a large number of men from getting tested for infertility, especially in resource-limited African countries. We describe the development and clinical testing of an automated smartphone-based semen analyzer designed for quantitative measurement of sperm concentration and motility for point-of-care male infertility screening. Using a total of 350 clinical semen specimens at a fertility clinic, we have shown that our assay can analyze an unwashed, unprocessed liquefied semen sample with <5-s mean processing time and provide the user a semen quality evaluation based on the World Health Organization (WHO) guidelines with ~98% accuracy. The work suggests that the integration of microfluidics, optical sensing accessories, and advances in consumer electronics, particularly smartphone capabilities, can make remote semen quality testing accessible to people in both developed and developing countries who have access to smartphones.

Concepts: Evaluation, Sperm, Semen analysis, Fertility, Spermatozoon, Semen, World Health Organization, Fertility medicine

63

Preexposure prophylaxis (PrEP) with emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) reduced HIV acquisition in the iPrEx trial among men who have sex with men and transgender women. Self-reported sexual risk behavior decreased overall, but may be affected by reporting bias. We evaluated potential risk compensation using biomarkers of sexual risk behavior.

Concepts: HIV, AIDS, Sexual intercourse, Gender, Semen, Oral sex, Human sexual behavior, Pre-exposure prophylaxis

40

There is growing evidence from animal and human studies that demonstrate that acquired paternal traits can impair both a male’s fertility and the health of his offspring, including advanced age, smoking, stress, trauma, under-nutrition, infection, toxin exposure, and obesity. Curiously, many of these factors manifest as impaired neurological, behavioural, and/or metabolic functioning in offspring. The underlying molecular mechanisms that respond to the paternal environment and act as vectors of intergenerational transmission are beginning to emerge. This review focuses on three vices of men (alcohol consumption, overweight/obesity, and tobacco smoking) that damage fertility and pose risks to offspring health. These vices are not only the three most prevalent but are also leading risk factors for death and disability adjusted life years (DALYs) worldwide. Clearly, any epigenetic/genetic alterations induced by the paternal exposures responsible for transmission need to escape/bypass the substantial post-fertilisation reprogramming that occurs during embryo development. For example paternal obesity alters the molecular composition of sperm, alters the developmental trajectory of resultant embryos, and increase the incidence of obesity and metabolic disorders in offspring. Mechanistic candidates of paternal programming include changes to the sperm epigenome (eg DNA methylation, histone/protamine modifications, and sperm borne small non-coding RNAs), increased sperm DNA damage, aberrant sperm DNA chromatin structure, and components of seminal plasma. Understanding the molecular mechanisms underpinning paternal programming may lead to the development of interventions designed to reduce the disease burden in future generations, who were born to fathers exposed to these initiating factors. Given that these vices are predominantly self-inflicted, interventions aimed at mitigating their consequences are readily identified.

Concepts: DNA, Cell nucleus, Gene expression, Histone, Epigenetics, Sperm, DNA methylation, Semen

40

The aim of this study was to investigate the effects of moderate-intensity continuous training (MICT), high-intensity continuous training (HICT) and high-intensity interval training (HIIT) on markers of male reproduction including seminal markers of oxidative stress and inflammation as well as semen quality and sperm DNA integrity in healthy human subjects. A total of 397 healthy male volunteers were screened and 280 were randomly assigned to one of the MICT (n = 70), HICT (n = 70), HIIT (n = 70) and non-exercise (NON-EX, n = 70) groups. Subjects had inflammatory markers (IL-1β, IL-6, IL-8 and TNF-α), oxidants (ROS, MDA and 8-isoprostane), antioxidants (SOD, catalase and TAC), semen parameters and sperm DNA damage measured at baseline (T1), the end of week 12 (T2), the end of week 24 (T3), and 7 (T4) and 30 days (T5) after training. Chronic MICT, HICT and HIIT attenuated seminal markers of oxidative stress and inflammation with different kinetics for the three types of exercise (P < 0.05), and these changes were correlated with favorable improvements in semen quality parameters and sperm DNA integrity (P < 0.05). MICT was superior to HICT and HIIT in the improvements of markers of male reproductive function (P < 0.05). In conclusion, different exercise modalities favorably affect markers of male reproduction with different kinetics, suggesting intensity-, duration- and type-dependent adaptations to exercise training in healthy human subjects.

Concepts: Immune system, Human, Reproduction, Sperm, Exercise, Spermatozoon, Semen, High-intensity interval training