Vitamin A deficiency results in meiotic failure and accumulation of undifferentiated spermatogonia in prepubertal mouse testis.
Vitamin A (retinol) is required for maintenance of adult mammalian spermatogenesis. In adult rodents, vitamin A withdrawal is followed by a loss of differentiated germ cells within the seminiferous epithelium and disrupted spermatogenesis that can be restored by vitamin A replacement. However, whether vitamin A plays a role in the differentiation and meiotic initiation of germ cells during the first round of mouse spermatogenesis is unknown. In the present study, we found that vitamin A depletion markedly decreased testicular expression of the all-trans retinoic acid-responsive gene, Stra8, and caused meiotic failure in prepubertal male mice lacking lecithin:retinol acyltransferase (Lrat), encoding for the major enzyme in liver responsible for the formation of retinyl esters. Rather than undergoing normal differentiation, germ cells accumulated in the testes of Lrat(-/-) mice maintained on a vitamin A-deficient diet. These results, together with our previous observations that germ cells fail to enter meiosis and remain undifferentiated in embryonic vitamin A-deficient ovaries, support the hypothesis that vitamin A regulates the initiation of meiosis I of both oogenesis and spermatogenesis in mammals.
Li
Hui
H
Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706-1544, USA.
Palczewski
Krzysztof
K
Baehr
Wolfgang
W
Clagett-Dame
Margaret
M
D000217:Acyltransferases / Q000172:deficiency; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002454:Cell Differentiation; D015536:Down-Regulation; D005260:Female; D008297:Male; D008540:Meiosis; D051379:Mice; D018345:Mice, Knockout; D011506:Proteins / Q000378:metabolism; D012741:Sexual Maturation; D013091:Spermatogenesis; D013093:Spermatogonia / Q000473:pathology*; D013737:Testis / Q000473:pathology*; D014801:Vitamin A / Q000378:metabolism; D014802:Vitamin A Deficiency / Q000473:pathology* / Q000503:physiopathology*
D048868:Adaptor Proteins, Signal Transducing; D011506:Proteins; C102019:Stra8 protein, mouse; D014801:Vitamin A; D000217:Acyltransferases; C056942:lecithin-retinol acyltransferase