Molecular Biology of Mammalian Gametogenesis, Fertilization and Early Development

National Institute Of Diabetes And Digestive And Kidney Diseases

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Abstract

Gonadogenesis: Female germ cells arrested at the prophase of the first meiotic division form follicles in which they are surrounded by somatic cells in the neonatal ovary. These follicles grow and asymmetrical cell division during meiosis ensures that ovulated eggs contain maternal factors necessary for successful development. Post-natal male germ cells maintain a spermatogonia stem cell niche within the testis from which cohorts are selected to undergo meiosis and are transmogrified into mature spermatozoa during spermiogenesis. Current studies investigate the roles of: 1) germ cell specific exosome RNases in ensuring egg maturation and early development; 2) male germ cell factors required for maintenance of spermatogonia stem cells; and 3) pachytene piRNAs required for spermiogenesis. Fertilization: The taxon-specificity of sperm-egg recognition in mammals that results in monospermic fertilization is mediated primarily by the zona pellucida, an extracellular matrix surrounding ovulated eggs. Although a simple structure of 3-4 glycoproteins, the molecular basis of sperm binding to the zona pellucida has been controversial. Current studies investigate: 1) molecular requirements to support taxon-specific sperm-egg recognition on the surface of the zona pellucida; 2) mechanism that result in acrosome exocytosis necessary for subsequent gamete fusion; and 3) the processes by which post-fertilization polyspermy is prevented. Early Development: Transcription that terminates during meiotic maturation in mouse eggs resumes only after robust activation of the embryonic genome of the two-cell embryo. This interregnum dictates a role for stored maternal factors in directing early development. Using gene-edited mice, the role of individual or complexes of maternal factor(s) is studied in these processes. Current research investigates: 1) a germ-cell specific initiation factor required for translation and zygotic gene activation; 2) loss of persistent, pervasive transcription essential for oocyte maturation and fertility; and 3) degradation of a maternal transcription inhibitor required for preimplantation cell differentiation.