Altered T lymphocyte subtypes and cytokine profiles in follicular fluid associated with diminished ovary reserve

Abstract

Problem: Diminished ovarian reserve (DOR) is a daunting obstacle in in vitro fertilization (IVF) or intra cytoplasmic sperm injection (ICSI), leading to poor reproductive outcomes. We aim to characterize the T cell and cytokine profiles in follicular fluid (FF) and elucidate its contribution to the development of DOR.

Method of study: A total of 92 infertile women were enrolled in the study. We assessed the ultrastructure, proliferation, and apoptosis of granulosa cells (GCs). The levels of CCL5 and cytokines in FF was measured. Additionally, we classified the T cells and analyzed cytokines production in T cell. We further verified whether CCL5 can recruit specific T cell subcytes to the follicles.

Results: Cytoplasmic vacuolization, nucleolar dissociation, partial shortening, swelling, and fusion of mitochondrial cristae were obvious in GCs with DOR. The proliferation of GCs decreased and the proportion of apoptosis increased in DOR. The down-regulation of Bcl-2 and up-regulation of caspase3 were seen in GCs with DOR. The number of CD8⁺ T cells and proportion of CD8⁺ /CD4⁺ T cells in DOR exceeded the control. Higher positive percentage of CD69, CCR5, and IFN-γ in CD8⁺ T cells, lower positive percentage of IL-10 in CD4⁺ T cells and PD-1 in CD8⁺ T cells were detected in DOR. CCL5 accumulated promoting the recruitment of CD8⁺ T cells to the follicles on interaction with CCR5.

Conclusion: The abnormal proportion of CD8⁺ T cells and elevated CCL5 and IFN-γ may change the immune balance in FF and impair the growth of GCs, which in turn fuel the progression of DOR.

Keywords: CCL5; CD8+ T lymphocytes; cytokine; diminished ovarian reserve; granulosa cells.