Cytological and genetic analysis of sexual dimorphism during meiotic prophase I in mammals

Date

2005

Authors

Kolas, Nadine Katherina

Journal Title

Journal ISSN

Volume Title

Publisher

ProQuest Dissertations & Theses

YU Faculty Profile

Abstract

Meiosis is the cell division pathway necessary for reducing cells with a diploid chromosome number to haploid germ cells required for sexual reproduction. Chromosome reduction during meiosis is accomplished by one replicative S-phase followed by two successive divisions. Meiotic prophase events that are necessary for proper chromosome segregation include: recognition and pairing of homologous chromosomes and, initiation and maturation of recombination between homologs. Many of the proteins that effect these two aspects of prophase have been identified in mammals, and other organisms, and are useful for characterizing the meiotic pathway in wild-type males and females and where meiosis is genetically altered.;Murine genetically targeted models indicate that female mammals are often differentially affected by meiotic disruption, maintaining full or partial fertility, while male meiosis fails causing infertility. This body of work explores the hypothesis that mammalian female fertility can overcome defects not affecting reciprocal recombination during prophase I. Cytological effects of mutations in two genes, the FK506 binding protein family member Fkbp6, and the mismatch repair MutL homolog Pms2, that both affect meiosis in a sexually dimorphic manner when deleted, are described here. Although deletion of either protein disrupts different aspects of meiosis in spermatocytes, oocytes proceed with normal reciprocal recombination and are fully fertile.;To explore the consequences of Pms2 and Fkbp6 mutations on the outcome of oocytes after prophase I, diakinesis, metaphase I chromosomal alignment, spindle development, and polar body extrusion were assessed. When FKBP6 or PMS2 is deleted oocytes proceed through the first meiotic division and arrest normally at the second metaphase plate, awaiting fertilization. By contrast, Mlh3 mutation disrupts reciprocal recombination sites and results in a drastically reduced ability for chromosomes to align during metaphase I, yet the oocytes do not arrest and instead continue to extrude a first polar body and become competent for fertilization. These data indicate that female meiotic spindle checkpoint regulation is less stringent than its male counterpart, perhaps due to evolution of a mechanism to overcome loss of some meiotic proteins, and may account for the bias in chromosomal abnormalities caused by errors in human female meiosis.

Description

Keywords

Cellular biology., Genetics.

Citation

Source: Dissertation Abstracts International, Volume: 66-02, Section: B, page: 6600.;Advisors: Paula E. Cohen.