Sterility and Gene Expression in Hybrid Males of Xenopus laevis and X. muelleri

BACKGROUND: Reproductive isolation is a defining characteristic of populations that represent unique biological species, yet we know very little about the gene expression basis for reproductive isolation. The advent of powerful molecular biology tools provides the ability to identify genes involved in reproductive isolation and focuses attention on the molecular mechanisms that separate biological species. Herein we quantify the sterility pattern of hybrid males in African Clawed Frogs (Xenopus) and apply microarray analysis of the expression pattern found in testes to identify genes that are misexpressed in hybrid males relative to their two parental species (Xenopus laevis and X. muelleri). METHODOLOGY/PRINCIPAL FINDINGS: Phenotypic characteristics of spermatogenesis in sterile male hybrids (X. laevis x X. muelleri) were examined using a novel sperm assay that allowed quantification of live, dead, and undifferentiated sperm cells, the number of motile vs. immotile sperm, and sperm morphology. Hybrids exhibited a dramatically lower abundance of mature sperm relative to the parental species. Hybrid spermatozoa were larger in size and accompanied by numerous undifferentiated sperm cells. Microarray analysis of gene expression in testes was combined with a correction for sequence divergence derived from genomic hybridizations to identify candidate genes involved in the sterility phenotype. Analysis of the transcriptome revealed a striking asymmetric pattern of misexpression. There were only about 140 genes misexpressed in hybrids compared to X. laevis but nearly 4,000 genes misexpressed in hybrids compared to X. muelleri. CONCLUSIONS/SIGNIFICANCE: Our results provide an important correlation between phenotypic characteristics of sperm and gene expression in sterile hybrid males. The broad pattern of gene misexpression suggests intriguing mechanisms creating the dominance pattern of the X. laevis genome in hybrids. These findings significantly contribute to growing evidence for allelic dominance in hybrids and have implications for the mechanism of species differentiation at the transcriptome level

The role of glucocorticoids in the regulation of thyroid function in man

The diurnal variation in thyroidal iodine release previously observed in euthyroid subjects appears to correlate with variations in serum immunoassayable thyrotropin (TSH). The hypothesis is advanced that this diurnal rhythm seems to be primarily regulated by a negative feedback action of circulating hydrocortisone. The administration of maintenance doses of hydrocortisone to patients with primary adrenal insufficiency and pharmacological doses to euthyroid subjects was accompanied by an acute suppression in both thyroidal iodine release and serum TSH values. An escape from glucocorticoid suppression was observed to occur in 2 or 3 days with the resumption of a near-normal thyroidal iodine release rate but was accompanied by a dampening or absence of the normal diurnal rhythm. Withdrawal of pharmacological doses of glucocorticoids in euthyroid subjects and maintenance doses in primary hypoadrenal patients was accompanied by transient stimulation of both serum TSH and thyroidal iodine release values. The study of a patient before and after cryohypophysectomy indicated that the rebound response in thyroid release after steroid withdrawal may be a useful testing procedure to indirectly assess the hypothalamicpituitary reserve capacity of TSH