Evidence for increasing incidence of abnormalities of the human testis: a review.

Recent reports have suggested that the incidence of genitourinary abnormalities in human males has increased during the past 50 years, including congenital abnormalities such as cryptorchidism and hypospadia, which seem to be occurring more commonly. Also, the incidence of testicular cancer has increased 3- to 4-fold since the 1940s. This increase seems to be worldwide including countries with a very high frequency of testicular neoplasia as well as those in which this cancer is rather uncommon. It has also been postulated that semen quality has been decreasing for the last half century. A recent study showed that the average sperm density has decreased significantly from 113 million/mL in 1940 to 66 million/mL in 1990. The mean seminal volume has also declined, indicating that the decrease in the total sperm count is even more pronounced than the fall in sperm density would indicate. The remarkable increase in frequency of testicular abnormalities over a relatively short period of time may be due to environmental rather than genetic factors. There is an epidemiological link between the occurrence of different testicular abnormalities. Therefore, common prenatally acting etiological factors with adverse effects on the fetal male gonad might be suspected. However, postnatal influences may also have a deleterious effect on male fertility. From the reproductive point of view, an increased impact on the human male gonad is of concern

Cryptorchidism and hypospadias in sons of gardeners and farmers.

Cryptorchidism and hypospadias have been related to prenatal estrogen exposure in animal models. Some chemicals used in farming and gardening have been shown to possess estrogenic and other hormone-disrupting effects. Earlier studies have indicated increased risks of urogenital malformations in the sons of pesticide appliers. In the present study, parental occupation in the farming and gardening industry among 6,177 cases of cryptorchidism, 1,345 cases of hypospadias, and 23,273 controls, born live from 1983 to 1992 in Denmark, was investigated in a register-based case-control study. A significantly increased risk of cryptorchidism but not hypospadias was found in sons of women working in gardening (adjusted odds ratio = 1.67; 95% confidence interval, 1.14-2.47). The risks were not increased in sons of men working in farming or gardening. The increased risk of cryptorchidism among sons of female gardeners could suggest an association with prenatal exposure to occupationally related chemicals

Quantification of the Leydig cell compartment in testicular biopsies and association with biochemical Leydig cell dysfunction in testicular cancer survivor

A simple histological method to evaluate the Leydig cell compartment is lacking. We aimed to establish such a method and to investigate if Leydig cell hyperplasia of the biopsy contralateral to the tumour-bearing testicle in patients with testicular germ cell cancer is associated with biochemical signs of Leydig cell dysfunction after long-term follow-up. A case group of 50 long-term testicular germ cell cancer survivors without human chorionic gonadotropin elevation, 10 testicular germ cell cancer patients with elevated human chorionic gonadotropin and 10 controls without testicular malignancy were included. For each subject, 2-4 representative sections from their testicular biopsies were selected for analysis. Using the image processing program ImageJ (V.1.48, NIH), an area with a minimum of 50 tubules was selected and delineated (total selected area) and the total Leydig cell area was calculated by adding up every delineated Leydig cell group within the total selected area. Four different methods were tested for the ability to quantify the Leydig cell compartment. In the 50 testicular germ cell cancer survivors, associations between the area of the Leydig cell compartment and serum levels of testosterone and luteinising hormone were investigated using linear regression analysis. The Leydig cell compartment was best quantified by the total Leydig cell area/total selected area index, which was significantly larger in the human chorionic gonadotropin-positive patients than in controls (P = 0.00001). In the 50 human chorionic gonadotropin-negative testicular germ cell cancer survivors, increasing total Leydig cell area/total selected area was significantly associated with decreased levels of total testosterone and decreased total testosterone/luteinising hormone ratio after a median of 9-year follow-up. In conclusion, a new simple method, total Leydig cell area/total selected area, was established to estimate the Leydig cell compartment in testicular biopsies. The index identified Leydig cell hyperplasia in the contralateral biopsy in patients with testicular germ cell cancer, and it was associated with long-term biochemical Leydig cell dysfunction. Although in testicular germ cell cancer survivors, the clinical value is limited because the contralateral biopsies are not commonly available, we propose a closer andrological follow-up in any patient with an increased total Leydig cell area/total selected area index

An update on semen quality among young Finnish men and comparison with Danish data

Finnish men used to have higher semen quality than Danish men. However, recent studies showed that semen quality in Finland has declined, but it has been relatively stable in Denmark.\nThis study aimed to compare new data on semen quality of the young Finnish men to that of Danish men.\nIn this cross-sectional study, 18- to 19-year-old men residing in Turku, Finland and Copenhagen, Denmark, were invited to participate in 2008-2011. Each man filled in a questionnaire, provided one semen sample and underwent andrological examination. Semen samples were analyzed according to WHO. Multiway ANOVA was used to adjust semen variables for duration of sexual abstinence and age (and time from ejaculation to the start of semen analysis for sperm motility).\nAltogether 287 Finnish men and 873 Danish men participated in the study. The adjusted median sperm concentrations were 49 and 47 million/mL for Finnish and Danish men, respectively (p = 0.48). The adjusted median total sperm counts were 148 million in Finland and 146 million in Denmark (p = 0.87). The adjusted median percentages of morphologically normal spermatozoa were 6.9% in Finland and 6.5% in Denmark, p = 0.27. Finnish men had higher adjusted median percentages of motile spermatozoa (A+B+C) than Danish men (80% vs. 69%, p < 0.001). The proportion of men who had low semen quality (sperm concentration, percentage of morphologically normal spermatozoa or percentage of progressively motile spermatozoa below WHO reference limits) was lower in Finland (25.4%) than in Denmark (34.6%), p = 0.004.\nConsiderable percentage of men in both countries had low semen quality. The deteriorating semen quality in Finland may result in decreasing fecundity, which is a cause of concern.\nThe formerly high semen quality in Finland has converged to the lower Danish levels. Our findings demonstrate the importance of continuing surveillance of semen quality.\nBACKGROUND\nOBJECTIVE\nMATERIALS AND METHODS\nRESULTS\nDISCUSSION\nCONCLUSIO

Maternal exposure to UV filters:Associations with maternal thyroid hormones, IGF-I/IGFBP3 and birth outcomes

Background: Several chemical UV filters/absorbers ('UV filters' hereafter) have endocrine-disrupting properties in vitro and in vivo. Exposure to these chemicals, especially during prenatal development, is of concern. Objectives: To examine maternal exposure to UV filters, associations with maternal thyroid hormone, with growth factor concentrations as well as to birth outcomes. Methods: Prospective study of 183 pregnant women with 2nd trimester serum and urine samples available. Maternal concentrations of the chemical UV filters benzophenone-1 (BP-1) and benzophenone-3 (BP-3) in urine and 4-hydroxy-benzophenone (4-HBP) in serum were measured by liquid chromatography–tandem mass spectrometry (LC–MS/MS). The relationships between 2nd trimester maternal concentrations of the three chemical UV filters and maternal serum concentrations of thyroid hormones and growth factors, as well as birth outcomes (weight, height, and head and abdominal circumferences) were examined. Results: Positive associations between maternal serum concentrations of 4-HBP and triiodothyronine (T3), thyroxine (T4), insulin-like growth factor I (IGF-I) and its binding protein IGFBP3 were observed in mothers carrying male fetuses. Male infants of mothers in the middle 4-HBP exposure group had statistically significantly lower weight and shorter head and abdominal circumferences at birth compared to the low exposure group. Conclusions: Widespread exposure of pregnant women to chemical UV filters and the possible impact on maternal thyroid hormones and growth factors, and on fetal growth, calls for further studies on possible long-term consequences of the exposure to UV filters on fetal development and children’s health

Data sharing: not as simple as it seems

In recent years there has been a major change on the part of funders, particularly in North America, so that data sharing is now considered to be the norm rather than the exception. We believe that data sharing is a good idea. However, we also believe that it is inappropriate to prescribe exactly when or how researchers should preserve and share data, since these issues are highly specific to each study, the nature of the data collected, who is requesting it, and what they intend to do with it. The level of ethical concern will vary according to the nature of the information, and the way in which it is collected - analyses of anonymised hospital admission records may carry a quite different ethical burden than analyses of potentially identifiable health information collected directly from the study participants. It is striking that most discussions about data sharing focus almost exclusively on issues of ownership (by the researchers or the funders) and efficiency (on the part of the funders). There is usually little discussion of the ethical issues involved in data sharing, and its implications for the study participants. Obtaining prior informed consent from the participants does not solve this problem, unless the informed consent process makes it completely clear what is being proposed, in which case most study participants would not agree. Thus, the undoubted benefits of data sharing does not remove the obligations and responsibilities that the original investigators hold for the people they invited to participate in the study