Developmental aspects of male reproductive health: clinical studies on semen quality, cryptorchidism, and puberty

Current evidence shows increasing rates of male reproductive disorders, including cryptorchidism, hypospadias, poor semen quality, decreased testosterone level, and testicular cancer. Therefore, studies on the physiology of the male reproductive system, and the current state of male reproductive health are necessary. In the first study, we followed the semen quality of young men for 10 years from the age of 19 years to see whether there are age-related changes in semen quality. In the second study, we compared the semen quality of young Finnish and Danish men to clarify possible differences between the countries. In the third study, we compared serum levels of reproductive hormones and insulin-like growth factor (IGF)-I) during puberty between individuals with and without a history of cryptorchidism to see whether a history of orchiopexy or delayed testicular descent is associated with alterations in the levels of these hormones. The first study showed that sperm concentration and total sperm count do not generally increase after 19 years, indicating that the maximum sperm production capacity is reached already in young adulthood. Sperm motility and morphology continue to improve after the age of 19 years. The second study showed that unlike in earlier studies, sperm concentrations, total sperm counts, and percentages of morphologically normal spermatozoa of Finnish and Danish men were now similar. However, Finnish men had better sperm motility. The third study showed that especially boys with a history of operated bilateral cryptorchidism had higher serum FSH and lower inhibin B levels than non-cryptorchid boys during puberty. These findings indicated an impaired Sertoli cell and/or germ cell function or number. Leydig cell function and the function of the growth hormone-IGF-I system were generally well-preserved during puberty in boys with a history of cryptorchidism.--- Miehen lisääntymisterveyteen liittyvien ongelmien, kuten kivesten laskeutumattomuuden (piilokiveksisyyden), virtsaputken alahalkioisuuden, kivessyövän, heikentyneen siemennesteen laadun sekä alhaisen testosteronipitoisuuden, on raportoitu yleistyneen. Tämän vuoksi tarvitaan tutkimuksia miehen lisääntymiselimistön normaalista toiminnasta sekä miesten lisääntymisterveyden nykytilasta. Väitöskirjan ensimmäisessä osatyössä selvitettiin tapahtuuko 19-vuotiaiden miesten siemennesteen laadussa muutoksia 10 vuoden seurannan aikana. Toisessa osatyössä verrattiin suomalaisten ja tanskalaisten nuorten miesten siemennesteen laatua, jotta nähtäisiin onko maiden välillä eroa siemennesteen laadussa. Kolmannessa osatyössä verrattiin piilokives- ja verrokkiryhmien sukupuolihormonien ja insuliinin kaltaisen kasvutekijä I:n (IGF-I) pitoisuuksia läpi murrosiän. Tässä viimeisessä osatyössä haluttiin selvittää, liittyykö hoidettuun tai spontaanisti parantuneeseen piilokiveksisyyteen muutoksia murrosiän hormoni- ja kasvutekijätasoissa. Ensimmäisessä osatyössä todettiin, että siemennesteen siittiöpitoisuus ja siittiömäärä eivät yleisesti kasva 19. ikävuoden jälkeen. Tämä viittaa siihen, että maksimaalinen siittiötuotantokapasiteetti saavutetaan jo varhaisessa aikuisiässä. Toisessa osatyössä havaittiin, että toisin kuin aiemmissa tutkimuksissa, suomalaisten ja tanskalaisten nuorten miesten välillä ei ollut enää eroa siittiöpitoisuudessa, siittiöiden kokonaismäärässä eikä normaalien siittiöiden määrässä. Suomalaisten nuorten miesten siittiöt liikkuivat kuitenkin paremmin kuin tanskalaisten miesten siittiöt. Kolmannessa osatyössä havaittiin, että etenkin leikkaushoitoa vaatineeseen molemminpuoliseen piilokiveksisyyteen liittyi murrosiässä verrokkeja suurempi follikkelia stimuloivan hormonin pitoisuus ja verrokkeja pienempi inhibiini B:n pitoisuus. Nämä viittaavat vähentyneeseen Sertolin solujen ja/tai itusolujen toimintaan tai määrään. Murrosiän aikainen Leydigin solujen ja IGF-I-kasvuhormoni -akselin toiminta oli yleisesti ottaen normaalia piilokivesryhmässä

Endocrine Disrupting Chemicals and Reproductive Health in Boys and Men

le reproductive health has declined as indicated by increasing rates of cryptorchidism, i.e., undescended testis, poor semen quality, low serum testosterone level, and testicular cancer. Exposure to endocrine disrupting chemicals (EDCs) has been proposed to have a role in this finding. In utero exposure to antiandrogenic EDCs, particularly at a sensitive period of fetal testicular development, the so-called ‘masculinization programming window (MPW)’, can disturb testicular development and function. Low androgen effect during the MPW can cause both short- and long-term reproductive disorders. A concurrent exposure to EDCs may also affect testicular function or damage testicular cells. Evidence from animal studies supports the role of endocrine disrupting chemicals in development of male reproductive disorders. However, evidence from epidemiological studies is relatively mixed. In this article, we review the current literature that evaluated relationship between prenatal EDC exposures and anogenital distance, cryptorchidism, and congenital penile abnormality called hypospadias. We review also studies on the association between early life and postnatal EDC exposure and semen quality, hypothalamic-pituitary-gonadal axis hormone levels and testicular cancer.</p

Determining the timing of pubertal onset via a multicohort analysis of growth

Objective Growth-based determination of pubertal onset timing would be cheap and practical. We aimed to determine this timing based on pubertal growth markers. Secondary aims were to estimate the differences in growth between cohorts and identify the role of overweight in onset timing. Design This multicohort study includes data from three Finnish cohorts-the Type 1 Diabetes Prediction and Prevention (DIPP, N = 2,825) Study, the Special Turku Coronary Risk Factor Intervention Project (STRIP, N = 711), and the Boy cohort (N = 66). Children were monitored for growth and Tanner staging (except in DIPP). Methods The growth data were analyzed using a Super-Imposition by Translation And Rotation growth curve model, and pubertal onset analyses were run using a time-to-pubertal onset model. Results The time-to-pubertal onset model used age at peak height velocity (aPHV), peak height velocity (PHV), and overweight status as covariates, with interaction between aPHV and overweight status for girls, and succeeded in determining the onset timing. Cross-validation showed a good agreement (71.0% for girls, 77.0% for boys) between the observed and predicted onset timings. Children in STRIP were taller overall (girls: 1.7 [95% CI: 0.9, 2.5] cm, boys: 1.0 [0.3, 2.2] cm) and had higher PHV values (girls: 0.13 [0.02, 0.25] cm/year, boys: 0.35 [0.21, 0.49] cm/year) than those in DIPP. Boys in the Boy cohort were taller (2.3 [0.3, 4.2] cm) compared with DIPP. Overweight girls showed pubertal onset at 1.0 [0.7, 1.4] year earlier compared with other girls. In boys, there was no such difference. Conclusions The novel modeling approach provides an opportunity to evaluate the Tanner breast/genital stage-based pubertal onset timing in cohort studies including longitudinal data on growth but lacking pubertal follow-up.Peer reviewe

Determining the timing of pubertal onset via a multicohort analysis of growth

ObjectiveGrowth-based determination of pubertal onset timing would be cheap and practical. We aimed to determine this timing based on pubertal growth markers. Secondary aims were to estimate the differences in growth between cohorts and identify the role of overweight in onset timing.DesignThis multicohort study includes data from three Finnish cohorts—the Type 1 Diabetes Prediction and Prevention (DIPP, N = 2,825) Study, the Special Turku Coronary Risk Factor Intervention Project (STRIP, N = 711), and the Boy cohort (N = 66). Children were monitored for growth and Tanner staging (except in DIPP).MethodsThe growth data were analyzed using a Super-Imposition by Translation And Rotation growth curve model, and pubertal onset analyses were run using a time-to-pubertal onset model.ResultsThe time-to-pubertal onset model used age at peak height velocity (aPHV), peak height velocity (PHV), and overweight status as covariates, with interaction between aPHV and overweight status for girls, and succeeded in determining the onset timing. Cross-validation showed a good agreement (71.0% for girls, 77.0% for boys) between the observed and predicted onset timings. Children in STRIP were taller overall (girls: 1.7 [95% CI: 0.9, 2.5] cm, boys: 1.0 [0.3, 2.2] cm) and had higher PHV values (girls: 0.13 [0.02, 0.25] cm/year, boys: 0.35 [0.21, 0.49] cm/year) than those in DIPP. Boys in the Boy cohort were taller (2.3 [0.3, 4.2] cm) compared with DIPP. Overweight girls showed pubertal onset at 1.0 [0.7, 1.4] year earlier compared with other girls. In boys, there was no such difference.ConclusionsThe novel modeling approach provides an opportunity to evaluate the Tanner breast/genital stage–based pubertal onset timing in cohort studies including longitudinal data on growth but lacking pubertal follow-up.</p

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 INTEREST(S): 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