Granulosa cells telomere analysis and follicular fluid protein profile in patients undergoing in vitro fertilization

• Grant number: 11/23975-1
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: April 01, 2012
• End date: March 31, 2013
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Ismael Dale Cotrim Guerreiro da Silva
• Grantee: Tatiana Carvalho de Souza Bonetti
• Supervisor: Celso Silva
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Institution abroad: University of South Florida (USF), United States

Abstract

The effect of increased age on fertility is well documented, with direct evidences for a temporal decline in ovarian performance with aging. However, the mechanisms by which aging interfere with oocyte quality are not yet complete understood. Abnormal chromosomal segregation is a potential explanation, but abnormal telomere biology has also been postulated as a causal determinant for biological aging. Telomeres shorten with every round of cell division, but telomere attrition is counterbalanced by the activation of telomerase, which synthetize telomeric tandem repeats onto the ends of chromosomes. Telomeres are also implicated in transcriptional reversible gene silencing of nearby genes, leading to telomere position effect (TPE), which can promote modifications in cell biology. Oogenesis and folliculogenesis are intrinsically dependent physiological processes. The follicle sustains oocyte development, and a complex mixture of proteins and other factors in the follicular fluid impact the oocyte's subsequent developmental potential. Thus, factors present in the follicular fluid and granulose cells are directly related to developing cumulus-oocyte complex. Oocytes do not possess telomerase activity, and previous studies demonstrate that telomere length in human unfertilized oocytes is correlated with embryonic quality and likelihood of pregnancy. Shorter telomeres and lack telomerase activity in granulose cell was associated with occult ovarian insufficiency. So, given the role of telomeres in controlling gene expression of sub-telomeric genes (TPE), it is expected that telomere attrition in either of these compartments will result in differential gene and protein expression. In this study, we propose to evaluate the relationship between granulose cells telomere length and telomerase activity with the protein profile of follicular fluid in patients undergoing In Vitro Fertilization (IVF). We hypothesize that telomere attrition will lead to a protein profile that is detrimental to adequate oocyte and embryonic developmental competence, which will result in lower IVF success rates. (AU)