Dysplastic Development of Seminiferous Tubules and Interstitial Tissue in Rat Hypogonadic (hgn/hgn) Testes1

Abstract

The hypogonadic rat is characterized by male sterility, reduced female fertility, and renal hypoplasia controlled by a single recessive allele (hgn) on chromosome 10. Plasma testosterone is low and levels of gonadotropins are high in adult male hgn/hgn rats, indicating that the cause of hypogonadism lies within the testis itself. We found that the postnatal growth of the seminiferous tubules was severely affected. Here we describe the details of postnatal testicular pathogenesis of the hgn/ hgn rats. In these rats, gonadal sex determination and initial differentiation of each type of testicular cell occur, but proliferation, differentiation, and maturation of these cells during postnatal testicular development is severely affected. Postnatal pathological changes include reduced proliferation and apoptotic cell death of Sertoli cells, abnormal mitosis and cell death of gonocytes, reduced deposition of extracellular matrix proteins into the basal lamina, lack of the formation of an outer basal lamina, formation of multiple layers of undifferentiated peritubular cells, and the delayed appearance and islet conformation of adult-type Leydig cells. Apoptotic cell death of Sertoli cells and disappearance of FSH receptor mRNA expression indicate that this mutant rat is a useful model for Sertoli cell dysfunction. The abnormalities listed above might be caused by defective interactions between Sertoli cells and other types of testicular cells. Because the results presented here strongly indicate that a normal allele for hgn encodes a factor playing a critical role in testicular development, the determination of the gene responsible for hgn and the analysis of early alterations of gene expression caused by mutations in this gene would provide important information on the mechanisms of testicular development.

Fine Mapping of the Region Including Hypogonadism (hgn) Locus on Rat Chromosome 10

“…Sci. 66(9): 1151-1154, 2004 Male hypogonadic rats (hgn/hgn) show severe hypogonadism that inherited as an autosomal single recessive manner. The weight of an adult hgn/hgn testis is almost equal to that of a normal female ovary and about 1% that of a normal rat testis.…”

“…In the present study, we performed further linkage analysis using 565 rat backcross progeny to make a fine linkage map around the hgn locus. Radiation Hybrid (RH) mapping was also performed to determine the order of the markers mapped at the same positions in the linkage analysis.All rats used in this study fed a certified commercial diet (CR-LPF: Oriental Yeast Co., Ltd., Tokyo, Japan) and were kept in a clean conventional animal room under controlled light (14L: 10D), temperature (22 ± 1°C), and humidity (55 ± 5%) [17]. The experimental procedure and care of animals were in accordance with the guideline of the Animal Care and Use Committee of Nippon Veterinary and Animal Science University.…”

“…All rats used in this study fed a certified commercial diet (CR-LPF: Oriental Yeast Co., Ltd., Tokyo, Japan) and were kept in a clean conventional animal room under controlled light (14L: 10D), temperature (22 ± 1°C), and humidity (55 ± 5%) [17]. The experimental procedure and care of animals were in accordance with the guideline of the Animal Care and Use Committee of Nippon Veterinary and Animal Science University.…”

“…Testicular pathogenesis begins in the fetal period and progresses during postnatal testicular development [20]. Most germ cells degenerate in the testes before entering meiosis because of Sertoli cell dysfunction [13,17]. hgn/hgn males show not only hypogonadism but also bilateral hypoplastic kidney (HPK) [19].…”

Duplicated insertion mutation in the microtubule-associated protein Spag5 (astrin/MAP126) and defective proliferation of immature Sertoli cells in rat hypogonadic (hgn/hgn) testes

“…Male hypogonadic (hgn/hgn) rats are characterized by male sterility resulting from testicular dysplasia , 1993, 2004b, a short female reproductive life resulting from ovarian hypoplasia (Suzuki et al 1992), progressive renal insufficiency resulting from renal hypoplasia (Suzuki & Suzuki 1995, Suzuki et al 1991, 2005, and body growth retardation (Suzuki et al 1992). All of these effects are controlled by a single recessive allele (hgn) located on chromosome 10 (Suzuki et al 1999(Suzuki et al , 2004a.…”