Effect of 1,25-dihydroxyvitamin d on testicular morphology and gene expression in experimental cryptorchid mouse: testis specific cDNA microarray analysis and potential implication in male infertility.
OBJECTIVE
We evaluated the morphological effect and alterations in gene expression caused by 1,25-dihydroxyvitamin D treatment in the mouse testis undergoing experimental cryptorchidism and subsequent orchiopexy.


METHODS
The mean modified Johnsen score and testicular weight were estimated after 4 weeks of treatment with a 1,25-dihydroxyvitamin D prodrug. We examined sites of vitamin D receptor and mRNA expression, and 1,25-dihydroxyvitamin D analogue accumulation in the mouse testis. Also, we compared alterations in gene expression in the cryptorchid mouse testis with or without 1,25-dihydroxyvitamin D administration by testis specific cDNA microarray. We confirmed protein synthesis of a candidate among up-regulated genes in primary cultures of Sertoli's cells by Western blotting.


RESULTS
Mean +/- SEM Johnsen score and testicular weight were increased by 1,25-dihydroxyvitamin D treatment but not significantly (6.12 +/- 0.33 vs 5.27 +/- 0.4 and 49.3 +/- 3.8 mg vs 42.6 +/- 5.5, p = 0.13 and 0.065, respectively). Vitamin D receptor and its mRNA were positive in Sertoli's cells. The 1,25-dihydroxyvitamin D analogue accumulated mainly in Sertoli's cells. Of 2,483 testis specific genes 19 showed up-regulation by 1,25-dihydroxyvitamin D treatment. Of these genes the regulator of cellular cholesterol homeostasis Abca1 was expressed mainly in Sertoli's cells and influenced male fertility. In primary cultures of Sertoli's cells the synthesis of Abca1 protein was increased by 1,25-dihydroxyvitamin D treatment but not by follicle-stimulating hormone or testosterone treatment.


CONCLUSIONS
We noted that 1,25-dihydroxyvitamin D contributes to spermatogenesis by up-regulating certain specific genes in Sertoli's cells. Testis specific cDNA microarray analysis and vitamin D supplementation may have implications for managing male infertility.
Hirai
Toshiaki
T
Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan.
Tsujimura
Akira
A
Ueda
Tomohiro
T
Fujita
Kazutoshi
K
Matsuoka
Yasuhiro
Y
Takao
Tetsuya
T
Miyagawa
Yasushi
Y
Koike
Nobuo
N
Okuyama
Akihiko
A
D000818:Animals; D003456:Cryptorchidism / Q000235:genetics* / Q000473:pathology*; D015870:Gene Expression / Q000187:drug effects*; D007248:Infertility, Male / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D013091:Spermatogenesis / Q000187:drug effects*; D013737:Testis / Q000187:drug effects* / Q000473:pathology*; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D