Difference in prevalence of congenital cryptorchidism in infants between two Nordic countries

Boisen, Kirsten A; Kaleva, Marko; Main, Katharina M.; Virtanen, HE; Am, Haavisto; Im, Schmidt; Chellakooty, Marla; In, Damgaard; C, Mau; Reunanen, Mikko; Ne, Skakkebæk; Toppari, Jorma

doi:10.1016/s0140-6736(04)15998-9

Cited by 459 publications

(447 citation statements)

References 28 publications

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“…There is a remarkably higher prevalence of cryptorchidism in Denmark compared with, for example, Finland (Fig. 6) (46). The prevalence in both populations falls by 3 months of age reflecting the effect of increased ambient testosterone levels at this time, but the prevalence of testis maldescent is still twofold greater in the Danish population.…”

Section: Environmental Factorsmentioning

confidence: 90%

Factors controlling testis descent

Hughes¹,

Acerini²

2008

European Journal of Endocrinology

136

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Descent of the testis from an intra-abdominal site in foetal life to an extracorporeal location after birth is a mandatory developmental process to ensure that the mature testis promotes normal spermatogenesis. The two phases of transabdominal and inguinoscrotal descent occur approximately during the first and last thirds of gestation respectively. Key anatomical events to release the testis from its urogenital ridge location and to guide the free gonad into the scrotum are the degeneration of the cranio-suspensory ligament and a thickening of the gubernaculum. Androgens play a role in both these processes, particularly with respect to enabling the testis to traverse the inguinal canal in the final phase of descent. Experiments in animals suggest that androgens mediate this effect via the release of calcitonin gene-related peptide by the genitofemoral nerve, but direct evidence for such a mechanism is lacking in humans. The transabdominal phase of descent is under the control of insulinlike 3 (INSL3), a product of the Leydig cells. Definitive evidence of its role in rodent testis descent is illustrated by the phenotype of bilateral cryptorchidism in Insl3K/K null mice. Circulating levels of INSL3 are higher in boys at puberty, are undetectable in girls and are lower in boys with undescended testes. A minority also have a mutation either in the INSL3 gene or affecting its receptor gene, relaxin/insulin-like family peptide receptor 2 (LGRF8). Other factors that may play a role in testis descent include the anti-Mullerian hormone and members of the HOX gene family. Evidence that the prevalence of undescended testis may be increasing provides a phenotypic readout for the effects of postulated chemicals in the environment interfering in some way with the action of factors that control testis descent. Epidemiological studies point to profound geographical variations in prevalence in countries such as Denmark and Finland. Associations have been found with levels of chemicals labelled as endocrine disruptors being higher in breast milk samples from mothers with cryptorchid boys when compared with controls. The adverse effects of these compounds (e.g. bisphenol A) can be replicated in the offspring of dams exposed during pregnancy. A sensitive marker of an anti-androgen effect of a compound is a reduction in the anogenital distance, an anthropometric measurement that is significantly greater in males compared with females. The observation of an association between the anogenital distance in infant boys and the level of pesticides in the urine of their mothers in late gestation indicates that this has the potential to be a useful surrogate marker of the effects of environmental chemicals on testis descent in human population studies. The rightful place for the testis at birth is in the scrotum in order to provide the temperature differential essential for normal spermatogenesis. Appropriate screening programmes and early surgical intervention are the prerequisites to ensure optimal fertility in adulthood and a con...

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Section: Environmental Factorsmentioning

confidence: 90%

Factors controlling testis descent

Hughes¹,

Acerini²

2008

European Journal of Endocrinology

136

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“…26 The incidence varies between 2 and 9% at birth (with some geographical variations across Europe) and decreases to 1-2% by 3 months of age due to delayed spontaneous descent. [27][28][29] However, cryptorchidism is found not only as a congenital disorder, but also as an acquired disorder diagnosed during infancy and childhood. 29,30 The so called "acquired cryptorchidism" is defined as the ascent of the testis into a cryptorchid position after normal scrotal position at birth and its cumulative incidence by age 24 months can be even higher than that observed at birth (in the UK congenital forms have a prevalence of 5.7% while "acquired" forms 7%).…”

Section: Varicocelementioning

confidence: 99%

Male infertility: Pathogenesis and clinical diagnosis

Krausz¹

2011

Best Practice & Research Clinical Endocrinology & Metab

400

315

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“…This finding proved controversial with additional analyses supporting (6-11) and contradicting (12)(13)(14) the original finding. Additional reports suggest that a rapid increase in testicular germ cell cancers, cryptorchidism, and other congenital anomalies in developed countries may be related to increased environmental estrogen exposure (15)(16)(17)(18). Additionally, recent animal model studies have indicated that environmental estrogens are capable of altering epigenetic patterns during early development with resulting gene expression changes, increased cancer susceptibility, and congenital aberrations as well as diminished reproductive capacity, compounding human health concerns (19,20).…”

mentioning

confidence: 99%

Aneuploid sperm formation in rainbow trout exposed to the environmental estrogen 17α-ethynylestradiol

Brown

Schultz

Cloud

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Environmental contaminants that mimic native estrogens (i.e., environmental estrogens) are known to significantly impact a wide range of vertebrate species and have been implicated as a source for increasing human male reproductive deficiencies and diseases. Despite the widespread occurrence of environmental estrogens and recognized detrimental effects on male vertebrate reproduction, no specific mechanism has been determined indicating how reduced fertility and/or fecundity is achieved. Previous studies show that male rainbow trout, Oncorhynchus mykiss, exposed to the environmental estrogen 17␣-ethynylestradiol (EE2) before gamete formation and fertilization produce progeny with significantly reduced embryonic survival. To determine whether this observed decrease results from sperm chromosome alterations during spermatogenesis, male rainbow trout were exposed to 10 ng of EE2/l for 50 days. After exposure, semen was collected and sperm aneuploidy levels analyzed with two chromosome markers by fluorescent in situ hybridization. In vitro fertilizations were also conducted by using control and exposed sperm crossed to eggs from an unexposed female for offspring analysis. Evaluations for nucleolar organizer region number and karyotype were performed on developing embryos to determine whether sperm aneuploidy translated into embryonic aneuploidy. Results conclusively show increased aneuploid sperm formation due to EE2 exposure. Additionally, embryonic cells from propagated progeny of individuals possessing elevated sperm aneuploidy display high levels of embryonic aneuploidy. This study concludes that EE2 exposure in sexually developing male rainbow trout increases levels of aneuploid sperm, providing a mechanism for decreased embryonic survival and ultimately diminished reproductive success in EE2 exposed males.aneuploidy ͉ EE2 ͉ xenoestrogens

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Difference in prevalence of congenital cryptorchidism in infants between two Nordic countries

Cited by 459 publications

References 28 publications

Factors controlling testis descent

Factors controlling testis descent

Male infertility: Pathogenesis and clinical diagnosis

Aneuploid sperm formation in rainbow trout exposed to the environmental estrogen 17α-ethynylestradiol

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