Sequential Expression of Type IV Collagen Networks: Testis as a Model and Relevance to Spermatogenesis

The six a chains of type IV collagen are organized into three networks: alpha 1/alpha 2, alpha 3/alpha 4/alpha 5, and alpha 1/alpha 2/alpha 5/alpha 6. A shift from the alpha 1/alpha 2 to the alpha 3/alpha 4/alpha 5 network occurs in the developing glomerular basement membrane, but how the alpha 1/alpha 2/alpha 5/alpha 6 network fits into this sequence is less clear, because the three networks do not colocalize. Here, we studied the seminiferous tubule basement membrane of normal canine testis where all three networks do colocalize: the alpha 1/alpha 2 network is expressed from birth, the alpha 1/alpha 2/alpha 5/alpha 6 network by 5-6 weeks of age, and the alpha 3/alpha 4/alpha 5 network by 2 months of age. A canine model of Alport syndrome allowed study of the absence of alpha 3/alpha 4/alpha 5 and alpha 1/alpha 2/alpha 5/alpha 6 networks in testis. In Alport dogs, the seminiferous tubule basement membrane was thinner than in controls. Spermatogenesis began at the same time as with normal dogs; however, the number of mature sperm was significantly reduced in Alport dogs. Thus, it would appear that alpha 3/ alpha 4/alpha 5 and alpha 1/alpha 2/alpha 5/alpha 6 networks are not essential for onset of spermatogenesis, but long-term function may be compromised by the loss of one or both networks. This situation is analogous to the glomerular basement membrane in Alport syndrome. In conclusion, testis can serve as a model system to study the sequence of type IV collagen network expression.