TSPY1 copy number variation influences spermatogenesis and shows differences among Y lineages.
BACKGROUND
TSPY1 is a tandemly-repeated gene on the human Y chromosome forming an array of approximately 21-35 copies. The testicular expression pattern and the inferred function of the TSPY1 protein suggest possible involvement in spermatogenesis. However, data are scarce on TSPY1 copy number variation in different Y lineages and its role in spermatogenesis.


OBJECTIVE
We sought to define: 1) the extent of TSPY1 copy number variation within and among Y chromosome haplogroups; and 2) the role of TSPY1 dosage in spermatogenic efficiency.


METHODS
A total of 154 idiopathic infertile men and 130 normozoospermic controls from Central Italy were analyzed. We used a quantitative PCR assay to measure TSPY1 copy number and also defined Y haplogroups in all subjects.


RESULTS
We provide evidence that TSPY1 copy number shows substantial variation among Y haplogroups and thus that population stratification does represent a potential bias in case-control association studies. We also found: 1) a significant positive correlation between TSPY1 copy number and sperm count (P < 0.001); 2) a significant difference in mean TSPY1 copy number between patients and controls (28.4 +/- 8.3 vs. 33.9 +/- 10.7; P < 0.001); and 3) a 1.5-fold increased risk of abnormal sperm parameters in men with less than 33 copies (P < 0.001).


CONCLUSIONS
TSPY copy number variation significantly influences spermatogenic efficiency. Low TSPY1 copy number is a new risk factor for male infertility with potential clinical consequences.
Giachini
Claudia
C
Andrology Unit, Department of Clinical Physiopathology, University of Florence, Florence 50139, Italy.
Nuti
Francesca
F
Turner
Daniel J
DJ
Laface
Ilaria
I
Xue
Yali
Y
Daguin
Fabrice
F
Forti
Gianni
G
Tyler-Smith
Chris
C
Krausz
Csilla
C
D000328:Adult; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics*; D041322:Chromosomes, Human, Y; D006801:Humans; D007248:Infertility, Male / Q000235:genetics*; D007558:Italy; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012307:Risk Factors; D013091:Spermatogenesis / Q000235:genetics*
D018797:Cell Cycle Proteins; C497749:TSPY1 protein, human