Influence of the hypogonadism (hgn) locus on female reproduction and ovarian development in an altered genetic background

Abstract

The hypogonadic rat () shows male sterility controlled by a single recessive gene . The females detected by the presence of renal hypoplasia in the HGN inbred strain show a reduced fertility. Recently, the gene responsible for male hypogonadism was mapped on chromosome 10 by a linkage analysis using only male backcross progeny. Because backcross females could not be categorized as affected or normal because of variations in their renal sizes, we could not examine female fertility in the backcross progeny. In the present experiment, we examined whether the gene mapped on rat chromosome 10 has any influences on female reproduction and ovarian development. The assumptive females were identified in the backcross progeny by microsatellite markers closely linked to the locus. Postnatal body growth, the weights of reproductive organs, estrus cycle and ovarian histology were examined. In addition, backcross embryos were genotyped, and their body growth and ovarian development was examined. The females showed growth retardation, a short reproductive life and an abnormal ovarian histology as adults. Regarding embryonic development, females showed body growth retardation and ovarian hypoplasia. The mutation of the mapped on chromosome 10 causes not only male sterility but also female reduced fertility related to ovarian hypoplasia beyond the altered genetic background. (Reprod Med Biol 2006; : 227-234).

Reduced Mitotic Activity and Increased Apoptosis of Fetal Sertoli Cells in Rat Hypogonadic (hgn/hgn) Testes

“…This was consistent with our observation that hgn/hgn ovaries were hypoplastic at ED 15.5 [21]. Since body growth is also retarded at ED 15.5 in female [21] and male [22] hgn/hgn fetuses, the mutated gene may have an early influence on whole body growth, including growth of the gonads, kidneys, and other organs.…”

“…This was consistent with our observation that hgn/hgn ovaries were hypoplastic at ED 15.5 [21]. Since body growth is also retarded at ED 15.5 in female [21] and male [22] hgn/hgn fetuses, the mutated gene may have an early influence on whole body growth, including growth of the gonads, kidneys, and other organs. Thereafter, ovarian hypoplasia does not progress to a more severe phenotype in hgn/hgn females [21], and these animals can retain reduced fertility as adults [5].…”

“…Since body growth is also retarded at ED 15.5 in female [21] and male [22] hgn/hgn fetuses, the mutated gene may have an early influence on whole body growth, including growth of the gonads, kidneys, and other organs. Thereafter, ovarian hypoplasia does not progress to a more severe phenotype in hgn/hgn females [21], and these animals can retain reduced fertility as adults [5]. In hgn/hgn males, however, testicular hypoplasia progresses to severe dysplasia, and these animals become sterile due to the complete absence of spermatogenesis as adults [18].…”

“…Mating success was confirmed the next day by the presence of sperm in a smear specimen, with 1600 h that day designated as embryonic day (ED) 0.5. At around 1600 h on ED 15.5, 17.5, 18.5 and 21.5, the pregnant rats were anesthetized by an overdose of ether and sacrificed by cervical dislocation, and the embryos were removed by cesarean section [21,22]. To assay cell mitotic activity, the pregnant rats were intraperitoneally injected with 5-bromo-2'-deoxyuridine (BrdU; 100 mg/kg, Sigma-Aldrich, St. Louis, MO, USA) at around 1400 h on ED 17.5 and 18.5.…”

“…Small pieces of tissue of each embryo were dissected and stored at -20 C. High-molecularweight genomic DNA was isolated from frozen tissues [8], and each embryo was classified as +/ hgn or hgn/hgn by genotyping for the D10Rat69 locus, which is closely linked to the hgn locus [9,21,22]. Polymerase chain reactions (PCRs), separation of PCR products, and gel staining were performed as described previously [23].…”