In this application, we proposed to investigate how a novel ovarian CD8aa+ cell population participates in important ovarian functions such as ovulation. Involvement of the immune system in ovarian functions has been recognized. The critical role of the thymus in ovarian functions is well known. Thus, athymic nude female mice are infertile, and thymectomy leads to ovarian dysfunctions. However, it remains unclear how the thymus participates in ovarian functions. We have identified a novel CD8aa+ population in the internal of antral follicles and their dramatic influx into the ovulating follicles during hCG-induced ovulation. This novel CD8aa+ cells probably originate from thymus and involved in important ovarian functions such as ovulation. Thus, transfer of syngeneic thymocytes, which contain several CD8aa+ cell populations, into the female nude mice restored their ovulatory ability. We next identified ovarian expression of chemokine TECK (thymus expressed chemokine) to be critical for the homing and influx of CD8aa+ cells into the ovary during ovulation. Thus, eliciting anti-TECK antibody by active immunization in the female BALB/c mice led to not only diminishment of the ovarian CD8aa+ cells but also infertility in the immunized mice. Based on the above results, we hypothesize a novel relationship between the thymus and the ovarian functions: 1) the novel CD8aa+ cells are originated from the thymus and recruited into the ovary by ovarian TECK, which is under hormonal regulation, and 2) the CD8aa+ cells are critical for ovulation/luteinization. This is intended to test out hypothesis by 1) determination of lineage and phenotype of ovarian CD8aa+, 2) identification of ovarian function that the ovarian CD8aa+ cells participate in, and 3) identification of TECK- expressing ovarian cells and determination of hormonal regulation of TECK expression in the ovary.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD049613-05
Application #
7858175
Study Section
Cellular, Molecular and Integrative Reproduction Study Section (CMIR)
Program Officer
Taymans, Susan
Project Start
2006-08-01
Project End
2012-05-31
Budget Start
2010-06-01
Budget End
2012-05-31
Support Year
5
Fiscal Year
2010
Total Cost
$232,227
Indirect Cost
Name
University of Texas Health Science Center Houston
Department
Other Basic Sciences
Type
Schools of Dentistry
DUNS #
800771594
City
Houston
State
TX
Country
United States
Zip Code
77225
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