A severe decline in child births has occurred over the past half century, which will lead to considerable population declines, particularly in industrialized regions. A crucial question is whether ...this decline can be explained by economic and behavioural factors alone, as suggested by demographic reports, or to what degree biological factors are also involved. Here, we discuss data suggesting that human reproductive health is deteriorating in industrialized regions. Widespread infertility and the need for assisted reproduction due to poor semen quality and/or oocyte failure are now major health issues. Other indicators of declining reproductive health include a worldwide increasing incidence in testicular cancer among young men and alterations in twinning frequency. There is also evidence of a parallel decline in rates of legal abortions, revealing a deterioration in total conception rates. Subtle alterations in fertility rates were already visible around 1900, and most industrialized regions now have rates below levels required to sustain their populations. We hypothesize that these reproductive health problems are partially linked to increasing human exposures to chemicals originating directly or indirectly from fossil fuels. If the current infertility epidemic is indeed linked to such exposures, decisive regulatory action underpinned by unconventional, interdisciplinary research collaborations will be needed to reverse the trends.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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.
Background: Perfluoroalkyl acids (PEAAs) are found globally in wildlife and humans and are suspected to act as endocrine disruptors. There are no previous reports of PFAA levels in adult men from ...Denmark or of a possible association between semen quality and PFAA exposure. Objectives: We investigated possible associations between PFAAs and testcular function. We hypothesized that higher PFAA levels would be associated with lower semen quality and lower testosterone levels. Methods: We analyzed serum samples for levels of 10 different PFAAs and reproductive hormones and assessed semen quality in 105 Danish men from the general population (median age, 19 years). Results: Considerable levels of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorohexane sulfonic acid were found in all young men (medians of 24.5, 4.9, and 6.6 ng/mL, respectively). Men with high combined levels of PFOS and PFOA had a median of 6.2 million normal spermatozoa in their ejaculate in contrast to 15.5 million among men with low PFOS-PFOA (p = 0.030). In addition, we found nonsignificant trends with regard to lower sperm concentration, lower total sperm counts, and altered pituitary-gonadal hormones among men with high PFOS-PFOA levels. Conclusion: High PFAA levels were associated with fewer normal sperm. Thus, high levels of PFAAs may contribute to the otherwise unexplained low semen quality often seen in young men. However, our findings need to be corroborated in larger studies.
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BFBNIB, DOBA, IZUM, KILJ, NMLJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Abstract
Context
The rapid pubertal height growth is unique to humans, but why do we have it? Although the spurt contributes 13% to 15% to the final adult height, we hypothesized that the biological ...significance of the high acromegalic levels of GH and IGF-I, which are behind the pubertal growth spurt, might primarily occur to stimulate the reproductive organs.
Evidence Synthesis
Animal data have demonstrated that adult Igf1 and Igf2 gene knockout mice that survive show a dramatic reduction in the size of the reproductive organs and are infertile. In humans, case reports of mutations in the genes affecting the GH–IGF axis and growth (GH, GHRH, GH-R, STAT5b, IGF-I, IGF-II, IGF-1R, PAPPA2) are also characterized by delayed pubertal onset and micropenis. Furthermore, GH treatment will tend to normalize the penile size in patients with GH deficiency. Thus, the endocrine effects of high IGF-I levels might be needed for the transition of the sexual organs, including the secondary sex characteristics, from the “dormant” stages of childhood into fully functioning reproductive systems. The peak IGF-I levels, on average, occur 2 years after the peak height growth velocity, suggesting reasons other than longitudinal growth for the high IGF-I levels, and remain high in the years after the height spurt, when the reproductive systems become fully functional.
Conclusion
We suggest that the serum levels of IGF-I should be monitored in children with poor development of sexual organs, although it remains to be investigated whether GH should be added to sex steroids in the management of hypogonadism for some pubertal children (e.g., boys with micropenis).
We hypothesized that the acromegalic levels of GH and IGF-I seen in normal puberty are needed, not only for optimal final height, but also primarily to secure genital growth.
Testicular cancer is the most common cancer among young men of European ancestry, with about one‐third of all cases occurring in Europe. With the historically increasing trends in some high‐incidence ...populations reported to have stabilised in recent years, we aimed to assess recent trends and predict the future testicular cancer incidence burden across Europe. We extracted testicular cancer (ICD‐10 C62) incidence data from Cancer Incidence in Five Continents Volumes VII–XI and complemented this with data published by registries from 28 European countries. We predicted cancer incidence rates and the number of incident cases in Europe in the year 2035 using the NORDPRED age‐period‐cohort model. Testicular cancer incidence rates will increase in 21 out of 28 countries over the period 2010–2035, with trends attenuating in the high‐incidence populations of Denmark, Norway, Switzerland and Austria. Although population ageing would be expected to reduce the number of cases, this demographic effect is outweighed by increasing risk, leading to an overall increase in the number of cases by 2035 in Europe, and by region (21, 13 and 32% in Northern, Western and Eastern Europe, respectively). Declines are however predicted in Italy and Spain, amounting to 12% less cases in 2035 in Southern Europe overall. In conclusion, the burden of testicular cancer incidence in Europe will continue to increase, particularly in historically lower‐risk countries. The largest increase in the number of testicular cancer patients is predicted in Eastern Europe, where survival is lower, reinforcing the need to ensure the provision of effective treatment across Europe.
What's new?
Testicular cancer (TC) is the most common cancer among young men of European ancestry. As the population ages, will rates of TC decrease? In this study, the authors found that, on the contrary, TC risk is predicted to rise in many European countries through the year 2035. The largest increase in the number of TC patients (32%) is predicted in Eastern Europe, where survival is also lower. These results reinforce the need to ensure that effective treatment is provided throughout Europe.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Recent publications showing unexpectedly early breast development in American girls created debate worldwide. However, secular trend analyses are often limited by poor data comparability among ...studies performed by different researchers in different time periods and populations. Here we present new European data systematically collected from the same region and by 1 research group at the beginning and end of the recent 15-year period.
Girls (N = 2095) aged 5.6 to 20.0 years were studied in 1991-1993 (1991 cohort; n = 1100) and 2006-2008 (2006 cohort; n = 995). All girls were evaluated by palpation of glandular breast, measurement of height and weight, and blood sampling (for estradiol, luteinizing hormone, and follicle-stimulating hormone). Age distribution at entering pubertal breast stages 2 through 5, pubic hair stages 2 through 5, and menarche was estimated for the 2 cohorts.
Onset of puberty, defined as mean estimated age at attainment of glandular breast tissue (Tanner breast stage 2+), occurred significantly earlier in the 2006 cohort (estimated mean age: 9.86 years) when compared with the 1991 cohort (estimated mean age: 10.88 years). The difference remained significant after adjustment for BMI. Estimated ages at menarche were 13.42 and 13.13 years in the 1991 and 2006 cohorts, respectively. Serum follicle-stimulating hormone and luteinizing hormone did not differ between the 2 cohorts at any age interval, whereas significantly lower estradiol levels were found in 8- to 10-year-old girls from the 2006 cohort compared with similarly aged girls from the 1991 cohort.
We found significantly earlier breast development among girls born more recently. Alterations in reproductive hormones and BMI did not explain these marked changes, which suggests that other factors yet to be identified may be involved.
Abstract Background Present knowledge on the impact of varicoceles on testicular function is largely based on studies of subfertile and infertile men, making it difficult to extrapolate the impact of ...varicocele on the general population. Objective To describe associations between varicocele and testicular function assessed by semen analysis and reproductive hormones in men from the general population. Design, setting, and participants A cross-sectional multicentre study of 7035 young men, median age 19 yr, from the general population in six European countries (Denmark, Finland, Germany, Estonia, Latvia, and Lithuania) were investigated from 1996 to 2010. Outcome measurements and statistical analysis We analysed results from physical examination, conventional semen variables, and serum reproductive hormones using multivariable regression analyses. Results and limitations A total of 1102 (15.7%) had grade 1–3 varicocele. Increasing varicocele grade was associated with poorer semen quality, even in grade 1 varicocele. In grade 3 varicocele, sperm concentration was less than half of that in men with no varicocele. Presence of varicocele was also associated with higher serum levels of follicle-stimulating hormone, lower inhibin B, and higher levels of luteinising hormone; testosterone and free testosterone were not significantly different between men with and without varicocele. This study cannot draw a conclusion on the progressiveness of varicocele or the effect of treatment. Conclusions We demonstrated an adverse effect of increasing grade of varicocele on testicular function in men not selected due to fertility status. Patient summary The presence and increasing grade of varicocele is adversely associated with semen quality and reproductive hormone levels in young men from the general population.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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Environmental chemicals and thyroid function Boas, Malene; Feldt-Rasmussen, Ulla; Skakkebæk, Niels E ...
European journal of endocrinology,
05/2006, Volume:
154, Issue:
5
Journal Article
Peer reviewed
Open access
There is growing evidence that environmental chemicals can disrupt endocrine systems. Most evidence originates from studies on reproductive organs. However, there is also suspicion that thyroid ...homeostasis may be disrupted. Several groups of chemicals have potential for thyroid disruption. There is substantial evidence that polychlorinated biphenyls, dioxins and furans cause hypothyroidism in exposed animals and that environmentally occurring doses affect human thyroid homeostasis. Similarly, flame retardants reduce peripheral thyroid hormone (TH) levels in rodents, but human studies are scarce. Studies also indicate thyroid-disruptive properties of phthalates, but the effect of certain phthalates seems to be stimulative on TH production, contrary to most other groups of chemicals. Thyroid disruption may be caused by a variety of mechanisms, as different chemicals interfere with the hypothalamic–pituitary–thyroid axis at different levels. Mechanisms of action may involve the sodium–iodide symporter, thyroid peroxidase enzyme, receptors for THs or TSH, transport proteins or cellular uptake mechanisms. The peripheral metabolism of the THs can be affected through effects on iodothyronine deiodinases or hepatic enzymes. Even small changes in thyroid homeostasis may adversely affect human health, and especially fetal neurological development may be vulnerable. It is therefore urgent to clarify whether the animal data showing effects of chemicals on thyroid function can be extended to humans.
Several non-persistent industrial chemicals have shown endocrine disrupting effects in animal studies and are suspected to be involved in human reproductive disorders. Among the non-persistent ...chemicals that have been discussed intensively during the past years are phthalates, bisphenol A (BPA), triclosan (TCS), and parabens because of their anti-androgenic and/or estrogenic effects. Phthalates are plasticizers used in numerous industrial products. Bisphenol A is the main component of polycarbonate plastics and epoxy resins. Parabens and TCS are antimicrobial preservatives and other phenols such as benzophenone-3 (BP-3) act as a UV-screener, while chlorophenols and phenyl phenols are used as pesticides and fungicides in agriculture. In spite of the widespread use of industrial chemicals, knowledge of exposure sources and human biomonitoring studies among different segments of the population is very limited. In Denmark, we have no survey programs for non-persistent environmental chemicals, unlike some countries such as the USA (NHANES) and Germany (GerES). However, we have analyzed the excretion of seven parabens, nine phenols, and the metabolites of eight different phthalates in urine samples collected over the past 6 years from four Danish cohorts. Here, we present biomonitoring data on more than 3600 Danish children, adolescents, young men, and pregnant women from the general population. Our study shows that nearly all Danes were exposed to the six most common phthalates, to BPA, TCS, and BP-3, and to at least two of the parabens. The exposure to other non-persistent chemicals was also widespread. Our data indicate decreasing excretion of two common phthalates (di-n-butyl phthalate and di-(2-ethylhexyl) phthalate) over time.
Ca2+-signaling controls sperm cell functions necessary for successful fertilization. Multiple endocrine disrupting chemicals have been found to interfere with normal Ca2+-signaling in human sperm ...cells through an activation of the sperm-specific CatSper Ca2+-channel, which is vital for normal male fertility.
We investigated 53 pesticides for their ability to interfere with CatSper mediated Ca2+-signaling and function in human sperm cells.
Effects of the pesticides on Ca2+-signaling in human sperm cells were evaluated using a Ca2+-fluorometric assay. Effects via CatSper were assessed using the specific CatSper inhibitor RU1968. Effects on human sperm function and viability were assessed using an image cytometry-based acrosome reaction assay and the modified Kremer’s sperm–mucus penetration assay.
28 of 53 pesticides were found to induce Ca2+-signals in human sperm cells at 10 µM. The majority of these 28 active pesticides induced Ca2+-signals through CatSper and interfered with subsequent Ca2+-signals induced by the two endogenous CatSper ligands progesterone and prostaglandin E1. Multiple active pesticides were found to affect Ca2+-mediated sperm functions and viability at 10 µM. Low nM dose mixtures of the active pesticides alone or in combination with other environmental chemicals were found to significantly induce Ca2+-signals and inhibit Ca2+-signals induced subsequently by progesterone and prostaglandin E1.
Our results show that pesticides, both alone and in low nM dose mixtures, interfere with normal Ca2+-signaling in human sperm cells in vitro in low nM concentrations. Biomonitoring of the active pesticides in relevant matrices such as blood and reproductive fluids is very limited and the effects of real time human pesticide exposure on human sperm cells and fertility thus remains largely unknown. To which extent human pesticide exposure affects the chances of a successful fertilization in humans in vivo needs further research.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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