Oocytes are formed before birth in humans, when primordial germ cells enter meiosis, the specialised cell division that will eventually give rise to a gamete. Female meiosis begins prenatally, but is not completed until the oocyte becomes fertilised, many years later. Meiosis is error-prone and important prenatal events, such as genetic recombination, may predispose the resulting oocyte to genetic abnormalities and aneuploidy. The consequences of prenatal events may therefore not be apparent until much later in life.
About 80% of early oocytes do not survive beyond birth in humans, so those that do are a selected population. The number of oocytes present in the ovary at birth is gradually eroded during pre- and post-pubertal life. The menopause takes place when the number of oocytes remaining reaches a critically low threshold. Only about 400 of the hundreds of thousands of oocytes formed are eventually ovulated.
The ovarian reserve of oocytes for reproductive life therefore depends critically upon the number and quality of oocytes formed before birth. We are studying oogenesis with a view to improving understanding of female meiosis, the factors affecting oocyte quality, and the process of apoptotic cell death which is responsible for the loss of most oocytes prenatally.
- Hartshorne GM, Lyrakou S, Hamoda H, Oloto E, Ghafari F. (2009) Oogenesis and cell death in human prenatal ovaries: what are the criteria for oocyte selection? Mol Hum Reprod. 2009 Dec;15(12):805-19.
- Ghafari F, Pelengaris S, Walters E, Hartshorne GM. (2009) Influence of p53 and genetic background on prenatal oogenesis and oocyte attrition in mice. Hum Reprod. 2009 Jun;24(6):1460-72 Free Text
- Ghafari F, Gutierrez C G, Hartshorne G M (2007) Apoptosis in mouse fetal & neonatal oocytes during meiotic prophase one, BMC Dev Biol. Jul 2007: 24; 7: p 87 Free Text
- Tease C, Hartshorne G M, Hulten M A (2006) Altered patterns of meiotic recombination in human fetal oocytes with asynapsis &/or synaptonemal complex fragmentation at pachytene, Reproductive Biomedicine Online 13(1); pp 88-95
- Tease C, Hartshorne G M, Hulten M A (2002) Patterns of meiotic recombination in human fetal oocytes, American Journal of Human Genetics 70; pp 1469-1479Free text
- Lyrakou S, Hulten M A, Hartshorne G M (2002) Growth factors promote meiosis in vitro in mouse fetal ovaries, Molecular Human Reproduction 8; pp 906-911 Free Text
- Hartshorne G M, Barlow A, Child T J, Barlow D H, Hulten M A (1999) Immunocytochemical detection of oocytes in human fetal ovarian tissue in vitro, Human Reproduction 14; pp 172-182 Free Text
Human primordial germ cells and early oocytes cultured for 4 days. Cytoplasm is highlighted with alkaline phosphatase, a germ-cell marker.
Human oocyte nucleus in the leptotene stage after several days in culture. Leptotene is the earliest stage of meiotic prophase I and this oocyte probably entered meiosis in vitro. The meiosis-specific synaptonemal complex is highlighted in green. Telomeres, marked red, are clustered in the characteristic leptotene bouquet on the right. Centromeres are highlighted in pink.
Graph showing mouse oocytes staining with cleaved PARP-1 (an apoptosis marker) and/or TUNEL (a marker of dsDNA breaks) at different stages of meiotic prophase I. This graph shows clearly that apoptosis occurs at all stages of meiotic prophase I (Ghafari et al, 2007).
Group leader and key contact
Prof Geraldine Hartshorne Professorial Fellow