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Germ cell development in the postnatal testis: the key to prevent malignancy in cryptorchidism?

Hutson JM, Li R, Southwell BR, Petersen BL, Thorup J, Cortes D - Front Endocrinol (Lausanne) (2013)

Bottom Line: Failure of any part of this process leads to congenital cryptorchidism, wherein the malpositioned testis finds itself at the wrong temperature after birth, which leads to secondary germ cell loss and later infertility and risk of cancer.Recent studies suggest that neonatal gonocytes transform into the putative spermatogenic stem cells between 3 and 9 months, and this initial postnatal step is deranged in cryptorchid testes.In addition, it is thought the abnormality high temperature may also impair apoptosis of remaining gonocytes, allowing some to persist to become the possible source of carcinoma in situ and malignancy after puberty.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Royal Children's Hospital Parkville, VIC, Australia.

ABSTRACT
To permit normal postnatal germ cell development, the mammalian testis undergoes a complex, multi-staged process of descent to the scrotum. Failure of any part of this process leads to congenital cryptorchidism, wherein the malpositioned testis finds itself at the wrong temperature after birth, which leads to secondary germ cell loss and later infertility and risk of cancer. Recent studies suggest that neonatal gonocytes transform into the putative spermatogenic stem cells between 3 and 9 months, and this initial postnatal step is deranged in cryptorchid testes. In addition, it is thought the abnormality high temperature may also impair apoptosis of remaining gonocytes, allowing some to persist to become the possible source of carcinoma in situ and malignancy after puberty. The biology of postnatal germ cell development is of intense interest, as it is likely to be the key to the optimal timing for orchidopexy.

No MeSH data available.


Related in: MedlinePlus

Testicular tissue from a 12-month-old boy with bilateral cryptorchidism. Carcinoma in situ (CIS) is suspected. (A) H&E staining: Sertoli cells are normal and the germ cell number is at the upper range for age. Some germ cells have two nuclei, and some nuclei have irregular morphology and some nucleolus. A microlith is clearly seen within a tubule. (B) Strong PLAP expression seen in all germ cells. (C) OCT4 expression in germ cells also in the periphery of tubules, which is not often seen so impressively in most cryptorchid testes at a similar age.
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Figure 7: Testicular tissue from a 12-month-old boy with bilateral cryptorchidism. Carcinoma in situ (CIS) is suspected. (A) H&E staining: Sertoli cells are normal and the germ cell number is at the upper range for age. Some germ cells have two nuclei, and some nuclei have irregular morphology and some nucleolus. A microlith is clearly seen within a tubule. (B) Strong PLAP expression seen in all germ cells. (C) OCT4 expression in germ cells also in the periphery of tubules, which is not often seen so impressively in most cryptorchid testes at a similar age.

Mentions: In a pediatric collective series of six studies, the risk of CIS in 2800 boys with cryptorchidism was 0.36% only (Cortes, 1998). When compared to higher incidence data from adults these pediatric figures support the hypothesis that the characteristics of CIS cells and later testicular cancer develops over time, and are not present from fetal life. Generally CIS in pediatric series is described in later childhood (Cortes et al., 1999). However, in this paper we present a 12-month-old boy with suspected CIS in bilateral cryptorchid testes (Figure 7). It has to be emphasized that positive immunohistochemical markers indicating CIS in the adult testis do not have such predictive value when applied to the childhood cryptorchid testis. Positive staining by such markers of persistent fetal germ cells is seen in almost half of the cryptorchid testes of boys younger than 5 years (Thorup et al., 2012). Presence of placental alkaline phosphatase (PLAP)-positive immunohistochemical stained gonocytes in bilateral cryptorchid testes of infant boys indicates the ability of delayed germ cell transformation and a preserved good fertility potential (Cortes et al., 2012). Further research in this field is therefore needed.


Germ cell development in the postnatal testis: the key to prevent malignancy in cryptorchidism?

Hutson JM, Li R, Southwell BR, Petersen BL, Thorup J, Cortes D - Front Endocrinol (Lausanne) (2013)

Testicular tissue from a 12-month-old boy with bilateral cryptorchidism. Carcinoma in situ (CIS) is suspected. (A) H&E staining: Sertoli cells are normal and the germ cell number is at the upper range for age. Some germ cells have two nuclei, and some nuclei have irregular morphology and some nucleolus. A microlith is clearly seen within a tubule. (B) Strong PLAP expression seen in all germ cells. (C) OCT4 expression in germ cells also in the periphery of tubules, which is not often seen so impressively in most cryptorchid testes at a similar age.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3539691&req=5

Figure 7: Testicular tissue from a 12-month-old boy with bilateral cryptorchidism. Carcinoma in situ (CIS) is suspected. (A) H&E staining: Sertoli cells are normal and the germ cell number is at the upper range for age. Some germ cells have two nuclei, and some nuclei have irregular morphology and some nucleolus. A microlith is clearly seen within a tubule. (B) Strong PLAP expression seen in all germ cells. (C) OCT4 expression in germ cells also in the periphery of tubules, which is not often seen so impressively in most cryptorchid testes at a similar age.
Mentions: In a pediatric collective series of six studies, the risk of CIS in 2800 boys with cryptorchidism was 0.36% only (Cortes, 1998). When compared to higher incidence data from adults these pediatric figures support the hypothesis that the characteristics of CIS cells and later testicular cancer develops over time, and are not present from fetal life. Generally CIS in pediatric series is described in later childhood (Cortes et al., 1999). However, in this paper we present a 12-month-old boy with suspected CIS in bilateral cryptorchid testes (Figure 7). It has to be emphasized that positive immunohistochemical markers indicating CIS in the adult testis do not have such predictive value when applied to the childhood cryptorchid testis. Positive staining by such markers of persistent fetal germ cells is seen in almost half of the cryptorchid testes of boys younger than 5 years (Thorup et al., 2012). Presence of placental alkaline phosphatase (PLAP)-positive immunohistochemical stained gonocytes in bilateral cryptorchid testes of infant boys indicates the ability of delayed germ cell transformation and a preserved good fertility potential (Cortes et al., 2012). Further research in this field is therefore needed.

Bottom Line: Failure of any part of this process leads to congenital cryptorchidism, wherein the malpositioned testis finds itself at the wrong temperature after birth, which leads to secondary germ cell loss and later infertility and risk of cancer.Recent studies suggest that neonatal gonocytes transform into the putative spermatogenic stem cells between 3 and 9 months, and this initial postnatal step is deranged in cryptorchid testes.In addition, it is thought the abnormality high temperature may also impair apoptosis of remaining gonocytes, allowing some to persist to become the possible source of carcinoma in situ and malignancy after puberty.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Royal Children's Hospital Parkville, VIC, Australia.

ABSTRACT
To permit normal postnatal germ cell development, the mammalian testis undergoes a complex, multi-staged process of descent to the scrotum. Failure of any part of this process leads to congenital cryptorchidism, wherein the malpositioned testis finds itself at the wrong temperature after birth, which leads to secondary germ cell loss and later infertility and risk of cancer. Recent studies suggest that neonatal gonocytes transform into the putative spermatogenic stem cells between 3 and 9 months, and this initial postnatal step is deranged in cryptorchid testes. In addition, it is thought the abnormality high temperature may also impair apoptosis of remaining gonocytes, allowing some to persist to become the possible source of carcinoma in situ and malignancy after puberty. The biology of postnatal germ cell development is of intense interest, as it is likely to be the key to the optimal timing for orchidopexy.

No MeSH data available.


Related in: MedlinePlus