Testicular dysgenesis syndrome and the origin of carcinoma in situ testis.
Recent increases in male reproductive disorders have been linked to exposure to environmental factors leading to the testicular dysgenesis syndrome (TDS). Testicular cancer is the most severe condition in TDS and studies have shown a clear correlation between risk of testicular cancer and other components of TDS and that the geographical location of the mother during pregnancy can be a risk factor. This suggests that the dysgenesis has its origin in utero and that TDS is initiated by environmental factors, including possibly hormone-disrupting compounds that act on the mother and the developing foetus, but the genetic background may also play a role. The morphological similarity of carcinoma in situ (CIS) cells (the precursor of the majority of invasive testicular cancers) with primordial germ cells and gonocytes, and overlap in expression of protein markers suggests an origin of CIS from primordial germ cells or gonocytes. CIS cells and germ cell-derived cancers of the human type have so far not been described in any animal model of TDS, which could be caused by species differences in the development of the male gonad. Regardless of this, it is plausible that the dysgenesis, and hence the development of CIS cells, is a result of disturbed signalling between nurse cells and germ cells that allow embryonic germ cells to survive in the pre-pubertal and adult testis. The post-pubertal proliferation of CIS cells combined with aberrant signalling then leads to an accumulation of genetic changes in the CIS cells, which eventually results in the development of invasive testicular cancer in the adult.
Sonne
Si Brask
SB
University Department of Growth and Reproduction, Rigshospitalet, Copenhagen, Denmark. si@bsonne.dk
Kristensen
David Møbjerg
DM
Novotny
Guy W
GW
Olesen
Inge Ahlmann
IA
Nielsen
John E
JE
Skakkebaek
Niels E
NE
Rajpert-De Meyts
Ewa
E
Leffers
Henrik
H
D006801:Humans; D008297:Male; D013577:Syndrome; D013736:Testicular Neoplasms / Q000209:etiology* / Q000473:pathology; D013737:Testis / Q000473:pathology*