Testicular dysgenesis syndrome: foetal origin of adult reproductive problems

Wohlfahrt-Veje, Christine; Main, Katharina M.; Skakkebæk, Niels E.

doi:10.1111/j.1365-2265.2009.03545.x

Cited by 165 publications

(122 citation statements)

References 70 publications

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“…This observation lead to the theory of the testicular dysgenesis syndrome which includes all the four above mentioned pathologies. 32 Congenital and acquired cryptorchidism are both very common but may have different etiology and consequences for fertility may also be different.…”

Section: Varicocelementioning

confidence: 99%

Male infertility: Pathogenesis and clinical diagnosis

Krausz¹

2011

Best Practice & Research Clinical Endocrinology & Metab

412

315

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Section: Varicocelementioning

confidence: 99%

Male infertility: Pathogenesis and clinical diagnosis

Krausz¹

2011

Best Practice & Research Clinical Endocrinology & Metab

412

315

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“…To what degree the environment, genetics, or epigenetics during fetal growth are responsible for TDS remains unresolved, but consensus is building concerning an expanded role for environmental influences and exposures (Virtanen et al, 2005;Wohlfahrt-Veje et al, 2009;Nordkap et al, 2012;Skakkebaek et al, 2016). Therefore, investigating semen parameters in relation to familial early-life mortality represents an area of novel contribution to the TDS hypothesis.…”

Section: Introductionmentioning

confidence: 99%

Risk of childhood mortality in family members of men with poor semen quality

et al. 2016

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STUDY QUESTION: What is the familial childhood mortality in first-degree (FDR) and second-degree relatives (SDR) of patients undergoing semen analysis (SA)?SUMMARY ANSWER: The relationship between infertility and congenital malformations (CM) in offspring is complex, with an increased risk of death due to CM in FDR, but not SDR, of men with lower semen parameters.WHAT IS KNOWN ALREADY: Semen quality is an established predictor of men's somatic health. We can gain a better understanding of possible genetic or environmental determinants of the infertility phenotype by exploring familial aggregation of childhood mortality in relatives of men with poor semen quality.STUDY DESIGN, SIZE, DURATION: Retrospective cohort study from the Subfertility, Health and Assisted Reproduction study (cohort compiled 1996-2011) linked with patient/familial information from the Utah Population Database (UPDB). Index cases included a clinicreferred sample of 12 889 men who underwent SA and had adequate familial and follow-up data in the UPDB. Parameters of semen quality included: semen concentration, sperm count, motility, total motile count, sperm head morphology, sperm tail morphology and vitality.PARTICIPANTS/MATERIALS, SETTING, METHODS: SA data were collected from two tertiary medical center andrology laboratories that have captured~90% of all SA performed in Utah since 2004. Age-and sex-matched fertile controls were selected to create the comparison group for determining risk of childhood death (to age 20 years) in family members. A total of 79 750 siblings and 160 016 aunts/ uncles were used to investigate the familial aggregation of childhood mortality. The main outcome was childhood mortality in FDR and SDR of men with SA and their matched controls. All-cause and cause-specific Cox proportional hazard models were used to test the association between semen quality and childhood mortality in family members. Cause-specific models were considered for cancer and CM. MAIN RESULTS AND THE ROLE OF CHANCE:In the cohort of men with SA, there were 406 (1.0%) deaths in FDR and 772 (1.1%) deaths in SDR due to any cause. There was no significant difference in the risk of all-cause childhood mortality between the relatives of men with SA and the fertile control group [hazard ratio (HR) Female = 1.08, 95% CI = 0.88, 1.32; HR Male = 0.88, 95% CI = 0.75, 1.04]. We found no association between semen quality and risk for childhood cancer mortality in FDR or SDR (HR FDR = 0.98, 95% CI = 0.62, 1.54; HR SDR = 1.12, 95% CI = 0.83, 1.50). The FDR of men with SA and fertile controls were followed on average for 19.71 and 19.73 years, respectively. During this period of follow-up, FDR of men with SA had an unadjusted 40% relative risk of increased CM-related death. After stratifying by semen parameters and adjusting for birth year, we found FDR of men with worse semen quality, and notably azoospermic men (HR = 2.69, 95% CI = 1.24,5.84), were at higher risk of CM-related death. LIMITATIONS REASONS FOR CAUTION:A large proportion of men with SA in the stu...

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“…Hence, increased understanding of Sertoli cell proliferation and development is important to those interested in animal agriculture. As abnormalities in Sertoli cell development and proliferation contribute to testicular dysgenesis syndrome in humans (Wohlfahrt-Veje et al 2009), increased understanding is also important to the biomedical community. Previous studies in our laboratory have demonstrated that the administration of letrozole, an inhibitor of estrogen synthesis, beginning in the neonatal period promotes proliferation of Sertoli cells in boars.…”

Section: Introductionmentioning

confidence: 99%

Stimulation of Sertoli cell proliferation: defining the response interval to an inhibitor of estrogen synthesis in the boar

et al. 2012

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Sertoli cell proliferation occurs in two major waves after birth, one neonatally and another prepubertally, each contributing to final testicular size and sperm production. However, little is known about the regulation of either wave. We have previously shown that letrozole, an inhibitor of estrogen synthesis, increases Sertoli cell number and testicular size at sexual maturity in boars. These studies were conducted to determine whether letrozole affects the first or second proliferative wave. Boars were treated with letrozole during the first wave (treatment at 1, 3, and 5 weeks), less frequently (1 week of age only, or 1 and 5 weeks), on postnatal day 1, or during the second wave (weeks 11-16). Sertoli cells were enumerated in testes and estrogen concentrations were evaluated in serum and testes. Compared with vehicle controls, letrozole reduced estrogen in boars treated at weeks 1 and 5 or 1, 3, and 5, on postnatal day 1, or prepubertally. However, Sertoli cell numbers were increased only in boars treated at 1, 3, and 5 weeks of age. Neither perinatal (1 day old) nor prepubertal letrozole treatment affected Sertoli cell numbers. Hence, Sertoli cell proliferation was sensitive to letrozole only if letrozole was administered throughout the first wave, even though estrogen synthesis was effectively inhibited at all ages. These data indicate that the neonatal but not the prepubertal window of Sertoli cell proliferation is sensitive to an inhibitor of estrogen synthesis; this suggests that these two waves are differently regulated.

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Testicular dysgenesis syndrome: foetal origin of adult reproductive problems

Cited by 165 publications

References 70 publications

Male infertility: Pathogenesis and clinical diagnosis

Male infertility: Pathogenesis and clinical diagnosis

Risk of childhood mortality in family members of men with poor semen quality

Stimulation of Sertoli cell proliferation: defining the response interval to an inhibitor of estrogen synthesis in the boar

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