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

The six α chains of type IV collagen are organized into three networks: α1/α2, α3/α4/α5, and α1/α2/α5/α6. A shift from the α1/α2 to the α3/α4/α5 network occurs in the developing glomerular basement membrane, but how the α1/α2/α5/α6 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 α1/α2 network is expressed from birth, the α1/α2/α5/α6 network by 5–6 weeks of age, and the α3/α4/α5 network by 2 months of age. A canine model of Alport syndrome allowed study of the absence of α3/α4/α5 and α1/α2/α5/α6 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 α3/α4/α5 and α1/α2/α5/α6 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.