Semen quality improves marginally during young adulthood: a longitudinal follow-up study.

STUDY QUESTION: Does semen quality improve during early adulthood? SUMMARY ANSWER: Semen variables change little during the third decade of life, however some improvement in sperm morphology and motility may occur. WHAT IS KNOWN ALREADY: A suspicion of deteriorating semen quality has been raised in several studies. The longitudinal development of semen quality in early adulthood is insufficiently understood. STUDY DESIGN, SIZE, DURATION: A longitudinal follow-up of two cohorts of volunteer young adult Finnish men representing the general population was carried out. Cohorts A (discovery cohort, born 1979-1981, n = 336) and B (validation cohort, born 1983, n = 197) were followed up from the age of 19 years onward for 10 years. PARTICIPANTS/MATERIALS, SETTING, METHODS: Inclusion criteria included that both the men and their mothers were born in Finland. Semen analysis was performed in cohorts A and B at 2-4 year intervals over a period of 10 years. Semen volume, sperm concentration, total sperm count, motility, total motile count and morphology were the variables assessed in the analysis. A physical examination was carried out at each visit to detect any significant andrological abnormalities. The overall participation rate was 13.4%. MAIN RESULTS AND THE ROLE OF CHANCE: During the follow-up, the percentage of sperm with normal morphology and the percentage of motile sperm increased significantly both in the discovery (A) (P < 0.001 at 19 versus 29 years for both) and validation (B) (P < 0.001 and P = 0.03 at 19 versus 29 years, respectively) cohort. Sperm concentration and total sperm count showed a significant increase with age only in cohort B (P = 0.03 at 21 versus 29 years, P = 0.009 at 19 versus 29 years, respectively). LIMITATIONS, REASONS FOR CAUTION: A limited number of men participated both in the first round and in the final fourth round (cohort A, n = 111 and cohort B, n = 90 men) and in all four rounds (cohort A, n = 61 and cohort B, n = 52). WIDER IMPLICATIONS OF THE FINDINGS: Almost full spermatogenic capacity is reached by the age of 19 years. However, the improvement in sperm motility and morphology during early adulthood may slightly improve male fecundity. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the European Commission (QLK4-CT-1999-01422, QLK4-CT-2001-00269, QLK4-2002-0063, FP7/2008-2012: DEER 212844), The Danish Medical Research Council (9700833, 9700909), Danish Agency for Science (Technology and Innovation 09-067180), the Svend Andersen's Foundation, Velux Foundation, and Novo Nordisk Foundation, the Turku University Hospital, Sigrid Jusélius Foundation and the Academy of Finland. There are no conflicts of interest.

Semen quality of 1559 young men from four cities in Japan: a cross-sectional population-based study.

OBJECTIVES: To provide information of semen quality among normal young Japanese men and indicate the frequency of reduced semen quality. DESIGN: Cross-sectional, coordinated studies of Japanese young men included from university areas. The men had to be 18-24 years, and both the man and his mother had to be born in Japan. Background information was obtained from questionnaires. Standardised and quality-controlled semen analyses were performed, reproductive hormones analysed centrally and results adjusted for confounding factors. SETTING: Four study centres in Japan (Kawasaki, Osaka, Kanazawa and Nagasaki). PARTICIPANTS: 1559 men, median age 21.1 years, included during 1999-2003. OUTCOME MEASURES: Semen volume, sperm concentration, total sperm count, sperm motility, sperm morphology and reproductive hormone levels. RESULTS: Median sperm concentration was 59 (95% CI 52 to 68) million/ml, and 9% and 31.9% had less than 15 and 40 million/ml, respectively. Median percentage of morphologically normal spermatozoa was 9.6 (8.8 to 10.3)%. Small, but statistically significant, differences were detected for both semen and reproductive hormone variables between men from the four cities. Overall, the semen values were lower than those of a reference population of 792 fertile Japanese men. CONCLUSIONS: Assuming that the investigated men were representative for young Japanese men, a significant proportion of the population had suboptimal semen quality with reduced fertility potential, and as a group they had lower semen quality than fertile men. However, the definitive role-if any-of low semen quality for subfertility and low fertility rates remain to be investigated.

Semen quality of fertile Japanese men: a cross-sectional population-based study of 792 men.

OBJECTIVES: To establish a base line for future studies on temporal trends, to describe potential geographical differences in semen quality and reference values for studies of men from the general population. DESIGN: Cross-sectional study of fertile men from four areas in Japan. Inclusion criteria were: age 20-45 years at the time of invitation, and both the man and his mother had to be born in Japan. Additionally, the current pregnancy of the female partner had to be achieved by normal sexual relations without any fertility treatment. SETTING: Four Japanese study centres at urban areas located in Sapporo, Osaka, Kanazawa and Fukuoka. PARTICIPANTS: 792 men, median age 31.4 years, included from 1999 to 2002. OUTCOME MEASURES: Semen volume, sperm concentration, total sperm count, sperm motility and sperm morphology. RESULTS: Semen volumes, percentages of motile spermatozoa and morphologically normal spermatozoa differed slightly between the four groups, whereas no differences in sperm concentrations or total sperm counts were found. In total, 1.2% of men had a sperm concentration below 5 million/ml, 2.1% below 10 million/ml, 3.5% below 15 million/ml and 16.3% below 40 million/ml. For morphology, 14.7% had less than 5% normal spermatozoa. Reproductive hormone levels varied significantly, however, only little from a biological point of view. CONCLUSIONS: This is the first cross-sectional study on semen quality covering fertile men from the major regions of Japan. It showed that semen quality of fertile Japanese men is comparable to that of the best in European regions. The results may serve as reference values for studies of men from the general population.

Serum inhibin-b in fertile men is strongly correlated with low but not high sperm counts: a coordinated study of 1,797 European and US men.

OBJECTIVE: To describe associations between serum inhibin-b and sperm counts, adjusted for effect of time of blood sampling, in larger cohorts than have been previously reported. DESIGN: Cross-sectional studies of spermatogenesis markers. SETTING: Four European and four US centers. PATIENT(S): Fertile men (1,797) were included and examined from October 1996-February 2005. INTERVENTION(S): The study was observational and therefore without any intervention. MAIN OUTCOME MEASURE(S): Associations between inhibin-b and semen variables controlled for time of blood sampling and other covariates. RESULT(S): Inhibin-b decreased about 2.00% per hour from 8 am-12 pm and then about 3.25% per hour from 12 pm-4 pm. There was a strong positive association between inhibin-b levels less than 150 pg/mL and both sperm concentration and total sperm count (slopes of the regression lines were ß=0.011 and ß=0.013 for natural logarithm-transformed sperm concentration and total sperm count, respectively). For inhibin-b levels of 150-300 pg/mL the associations were not as steep (ß=0.002), but still significant. For inhibin-b levels more than 300 pg/mL there was little association to the sperm counts. Neither sperm motility nor morphology was significantly related to inhibin-b level in any group. CONCLUSION(S): Serum inhibin-b levels decrease nonlinearly during the daytime, and are positively correlated with sperm counts, but the predictive power is best when inhibin-b is low.

Semen quality in sub-fertile range for a significant proportion of young men from the general German population: a co-ordinated, controlled study of 791 men from Hamburg and Leipzig.

Population studies have shown that a high proportion of Nordic men may have so poor semen quality that they can be classified as sub-fertile according to international standards. A question is whether the Nordic data are specific for the Nordic countries or they should be seen as an expression of a general trend in Europe. We therefore carried out a prospective study of semen quality of young men raised in the former East Germany (Leipzig) and West Germany (Hamburg). To enable inter-regional comparisons, we utilized a common European research protocol previously used in studies in the Nordic-Baltic region. Three hundred and thirty-four young men representative of the general population from Hamburg, and 457 from Leipzig delivered semen samples, underwent physical examinations and provided information on life-style and reproductive health parameters. The study period in Hamburg was February 2003--July 2004, and in Leipzig July 2003--April 2005. No significant differences were observed in sperm concentration (median 46, 42, and 44 million/mL for men from Hamburg, Leipzig and the combined Hamburg-Leipzig group respectively) or total sperm count (154,141 and 149 million), whereas the differences for morphologically normal spermatozoa (9.4 and 8.4%) and motile spermatozoa (67 and 81%) were significantly different. Previously published studies have shown reduced fertility with decreasing sperm concentrations below 40-55 millions/mL and normal sperm morphology below 9-19%. Thus, a large fraction of young German men seem to have impaired semen quality that may reduce their natural fertility. However, it remains to be investigated to what extent poor semen quality contributes to the low German fertility rates.

Association of in utero exposure to maternal smoking with reduced semen quality and testis size in adulthood: a cross-sectional study of 1,770 young men from the general population in five European countries.

Between 1996 and 1999, the authors invited all young men from five European countries who were undergoing compulsory medical examination for possible military service to participate in a study on male reproductive health. The participation rate was 19% in two cities in Denmark (n = 889), 17% in Oslo, Norway (n = 221), 13% in Turku, Finland (n = 313), 14% in Kaunas, Lithuania (n = 157), and 19% in Tartu, Estonia (n = 190). Each man provided a semen sample, was examined by a physician, and, in collaboration with his mother, completed a questionnaire about general and reproductive health, current smoking habits, and exposure to smoking in utero. After adjustment for confounding factors, men exposed to smoking in utero had a reduction in sperm concentration of 20.1% (95% confidence interval (CI): 6.8, 33.5) and a reduction in total sperm count of 24.5% (95% CI: 9.5, 39.5) in comparison with unexposed men. Percentages of motile and morphologically normal sperm cells were 1.85 (95% CI: 0.46, 3.23) and 0.64 (95% CI: -0.02, 1.30) percentage points lower, respectively, among men exposed in utero, and exposed men had a 1.15-ml (95% CI: 0.66, 1.64) smaller testis size. The associations were present when data from the study centers were analyzed separately (though not in Lithuania, where only 1% of mothers smoked during pregnancy), although the strength of the association varied. Maternal smoking may have long-term implications for the reproductive health of the offspring. This is another good reason to advise pregnant women to avoid smoking.

Adenosine triphosphate induces Ca2+ signal in epithelial cells of the mouse caput epididymis through activation of P2X and P2Y purinergic receptors.

In the present study, we developed a novel method to analyze the calcium (Ca2+) signal in living slices of mouse caput epididymides by applying calcium imaging on Fura-2-loaded vibratome slices. The data revealed that in epithelial cells of mouse caput epididymides, ATP induces a rapid Ca2+ signal that is sustained after 60 sec. Preincubating the sections in Ca2+-free medium in the presence of EGTA did not affect the amplitude of the ATP-induced Ca2+ signal, indicating the presence of P2Y type purinergic receptors and phospholipase C activity. Furthermore, ATP induced a similar Ca2+ signal in the different subregions of caput epididymides. The P2X type ion-gated purinergic receptors could also be responsible for the ATP-induced Ca2+ signal because immunohistochemical and reverse transcriptase-polymerase chain reaction analyses showed that P2X1, P2X2, P2X4, P2X7, P2Y1, and P2Y2 receptors were expressed in the epididymis. We propose that P2X and P2Y receptor expression is vital for the normal function of epididymal epithelium and sperm maturation. Furthermore, the method we developed allows us to analyze the activity of various G protein-coupled receptors in intact epithelial cells of mouse epididymides, and other reproductive tissues as well.

Hereditary sterilizing short-tail sperm defect in Finnish Yorkshire boars.

A new infertility syndrome has recently been described in Finnish Yorkshire boars. Typical for the syndrome is total akinesia and severe tail malformation of the spermatozoa. Morphometric analysis was performed on semen smears from 20 affected and 18 control boars and on testicular tissue sections from 5 affected and 4 control boars. Semen morphometry revealed that, in affected boars, the length of the sperm tails was only 33% of that of the controls (15.4 microm vs. 47.0 microm, P < 0.0001). Typical for the spermatozoa of affected boars was also an abundant frequency of proximal cytoplasmic droplets (72.4% vs. 6.9%, P < 0.0001), whereas no major sperm-head abnormalities were recorded. In the testicular tissue samples, viewed at light microscopic level, the volume densities of seminiferous tubules or interstitium did not differ. The most characteristic change in the seminiferous epithelium of the affected boars was a reduced number of elongated spermatids. Densities of Sertoli cells and Leydig cells between affected and control boars did not differ. The ultrastructure of testicular tissue from affected boars showed severe alterations in the assembly of the midpiece and tail of the spermatozoa. As well, a typical finding in the seminiferous epithelium of affected boars was conspicuous deposition of lipid droplets. The pathogenesis of this syndrome severely affects spermiogenesis and motility. Spermatozoa have malformed, short tails, which never become motile. This syndrome is not manifested in the structure or function of other ciliated cells in the affected animals.

East-West gradient in semen quality in the Nordic-Baltic area: a study of men from the general population in Denmark, Norway, Estonia and Finland.

BACKGROUND: Denmark and Norway have a three-fold higher incidence of testicular cancer than Estonia and Finland. Groups of young men from Denmark, Norway, Finland and Estonia were investigated to elucidate whether semen parameters and other related parameters follow a gradient between these countries, as does the gradient in incidence of testicular cancer. METHODS: In total, 968 young men from the general population in these four countries were investigated according to the same protocol. Possible confounders were evaluated, and included in the statistical analysis when appropriate. Inter-laboratory differences in assessment of sperm concentrations were controlled by an external quality control programme and morphology assessment was centralized to one person. RESULTS: The Finnish and Estonian men had an adjusted median sperm concentration of 54 and 57 x 10(6)/ml, respectively and the Norwegian and Danish men 41 x 10(6)/ml. The corresponding total sperm counts were 185, 174, 133 and 144 x 10(6). The frequency of normal sperm in men from Finland was 8.9%, Estonia 9.2%, Norway 6.9% and Denmark 6.4%. Within all four groups of men, a relationship between increasing levels of inhibin-B and increasing sperm counts was observed. However, inhibin-B levels were not predictive of sperm count differences between countries. CONCLUSIONS: It is believed that the men examined were representative of the normal population of young men in all four countries as they were recruited from groups attending a compulsory medical examination, and not selected for known fertility or semen quality. Moreover, the majority of participants had no prior knowledge of their fertility potential. It appears that an east-west gradient exists in the Nordic-Baltic area with regard to semen parameters, this being in parallel with the incidences of testicular cancer. Further investigations are required to determine whether these findings are due to genetic differences, to different environments, or perhaps to a combination of both factors.