Cancer treatment in childhood and testicular function: the importance of the somatic environment

Stukenborg, Jan-Bernd; Jahnukainen, Kirsi; Hutka, Marsida; Mitchell, Rod

doi:10.1530/ec-17-0382

Cited by 60 publications

(58 citation statements)

References 143 publications

(209 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Unlike in the female, where the two are intimately connected, they are distinct in the male, and spermatogenesis (supported by normal Sertoli cell function) can be impaired without manifest damage to steroidogenesis (Leydig cell function). However, although survival of the germ cells is crucial for future fertility, the somatic stem cells (Sertoli cells) are important for fertility, as they create the environment that is needed to support development and survival of the germ cells [31]. As in females, the risk of treatment-related gonadotoxicity in males may cause emotional distress, with decreased testosterone concentrations leading to pubertal delay, or impaired spermatogenesis leading to reduced or lost fertility.…”

Section: Primary Gonadal Failure In Male Ccs (Table 1)mentioning

confidence: 99%

“…Primary gonadal failure with androgen deficiency and impaired spermatogenesis may be the result of the tumor itself (testis tumor), or its treatment. Surgery, chemotherapy or radiation to the testes may all lead to testicular dysfunction due to direct damage to Leydig-, Sertoli- or the testicular germ cells [7, 31]. Indirect damage may also cause dysfunction of the Sertoli or Leydig cells, such as by vascular damage, damage by changes in hormone concentrations, growth factors or the structure of the seminiferous tubule structure that will indirectly mediate the effects of chemo-/radiotherapy on the germ cells.…”

Section: Primary Gonadal Failure In Male Ccs (Table 1)mentioning

confidence: 99%

See 1 more Smart Citation

Hypogonadism in Children with a Previous History of Cancer: Endocrine Management and Follow-Up

et al. 2019

View full text Add to dashboard Cite

Hypogonadism after treatment for childhood cancer is a recognized complication and its cause may be subdivided into primary gonadal failure and central hypogonadism. Here, we provide an overview of the risk factors for the development of hypogonadism, assessment and potential interventions and give a summary of the current recommendations for management and follow-up of hypogonadism in childhood cancer survivors.

show abstract

Section: Primary Gonadal Failure In Male Ccs (Table 1)mentioning

confidence: 99%

Section: Primary Gonadal Failure In Male Ccs (Table 1)mentioning

confidence: 99%

Hypogonadism in Children with a Previous History of Cancer: Endocrine Management and Follow-Up

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Sertoli cells contribute fundamentally to the stem cell niche and the regulatory control of spermatogenesis (Wistuba et al ., ). Sertoli cells are ought to exhibit almost no proliferative and/or no regenerative capacity in the adult testis (Sharpe et al ., ; Stukenborg et al ., ). Thus, it could be assumed that Sertoli cells should be susceptible to age‐dependent alterations.…”

Section: Introductionmentioning

confidence: 97%

Ageing in men with normal spermatogenesis alters spermatogonial dynamics and nuclear morphology in Sertoli cells

et al. 2019

View full text Add to dashboard Cite

Background: Ageing in men is believed to be associated with fertility decline and elevated risk of congenital disorders for the offspring. The previous studies also reported reduced germ and Sertoli cell numbers in older men. However, it is not clear whether ageing in men with normal spermatogenesis affects the testis and germ cell population dynamics in a way sufficient for transmitting adverse age effects to the offspring. Objectives: We examined men with normal spermatogenesis at different ages concerning effects on persisting testicular cell types, that is the germ line and Sertoli cells, as these cell populations are prone to be exposed to age effects. Material and methods: Ageing was assessed in testicular biopsies of 32 patients assigned to three age groups: (i) 28.8 AE 2.7 years; (ii) 48.1 AE 1 years; and (iii) 70.9 AE 6.2 years, n = 8 each, with normal spermatogenesis according to the Bergmann-Kliesch score, and in a group of meiotic arrest patients (29.9 AE 3.8 years, n = 8) to decipher potential links between different germ cell types. Besides morphometry of seminiferous tubules and Sertoli cell nuclei, we investigated spermatogenic output/efficiency, and dynamics of spermatogonial populations via immunohistochemistry for MAGE A4, PCNA, CREM and quantified A-pale/A-dark spermatogonia. Results: We found a constant spermatogenic output (CREM-positive round spermatids) in all age groups studied. In men beyond their mid-40s (group 2), we detected increased nuclear and nucleolar size in Sertoli cells, indirectly indicating an elevated protein turnover. From the 7th decade (group 3) of life onwards, testes showed increased proliferation of undifferentiated spermatogonia, decreased spermatogenic efficiency and elevated numbers of proliferating A-dark spermatogonia. Discussion and conclusion: Maintaining normal sperm output seems to be an intrinsic determinant of spermatogenesis. Ageing appears to affect this output and might provoke compensatory proliferation increase in A spermatogonia which, in turn, might hamper germ cell integrity.

show abstract

“…In males, the testis is the site of production of mature spermatozoa and testosterone. Given that cancer treatments can target both healthy and cancerous cell lines the spermatogonia and supporting cells are at risk of damage . However, testosterone‐producing, Leydig cells are more resistant to anticancer treatments than the germinal cell lines .…”

Section: Cancer and Fertilitymentioning

confidence: 99%

“…Based on Green et al; 58 Green et al; 76 Green et al; 77 Green et al; 78 and Bath et al 79 cells are at risk of damage. 50 However, testosterone-producing, Leydig cells are more resistant to anticancer treatments than the germinal cell lines. [51][52][53] Consequently most prepubertal male patients who receive cancer treatment will achieve normal pubertal development.…”

Section: Disruption Of Hypothalamicpituitary-gonadal Axismentioning

confidence: 99%

Survival from cancer in young people: An overview of late effects focusing on reproductive health

Newton

Friend

Feltbower

et al. 2019

Acta Obstet Gynecol Scand

View full text Add to dashboard Cite

This paper provides a summary of the areas of survival from childhood, teenage and young adult cancers and the significant late effects that can arise from treatment; with particular focus on the area of reproductive health and the impact on both fertility and pregnancy. To complete this review, Web of Science and MEDLINE were used. Search terms included: “"survival AND childhood OR teenage OR young adult cancer", "late effects", "childhood cancer", "teenage AND/OR young adult cancer", AND "fertility after cancer" OR "pregnancy AND cancer" OR "fertility preservation”. Additionally, the clinical expertise of the authors was drawn upon. Childhood cancer is a thankfully rare occurrence; however, the incidence is increasing. Survival rates remain high and this means that a growing population of childhood and young adult cancer survivors are reaching adulthood. For some of these adults, although cured of their cancer, they are now facing a future with lasting effects on their health from their treatments. These effects, commonly referred to as late effects, are defined as health problems related either directly to the underlying cancer or to its treatment and which occur months or years after treatment has finished. Reproductive health is an important consideration for these patients, and although many will be able to conceive naturally, some will exhibit impaired fertility after their treatments. This can include difficulties at all points along the path from conception to delivery of a live, healthy offspring. High‐quality, large‐population evidence is sparse in many areas relating to fertility risk from treatment and the maternal and fetal health of childhood cancer survivors. Yet given the potential for complications, the authors advocate consideration of fertility at the time of diagnosis and before potentially gonadotoxic treatment.

show abstract

Cancer treatment in childhood and testicular function: the importance of the somatic environment

Cited by 60 publications

References 143 publications

Hypogonadism in Children with a Previous History of Cancer: Endocrine Management and Follow-Up

Hypogonadism in Children with a Previous History of Cancer: Endocrine Management and Follow-Up

Ageing in men with normal spermatogenesis alters spermatogonial dynamics and nuclear morphology in Sertoli cells

Survival from cancer in young people: An overview of late effects focusing on reproductive health

Contact Info

Product

Resources

About