P-670 Altered immunological conditions in women with PCOS and its correlation with the development and progression in infertile women with severe polycystic ovaries
Authors: Jing G , Sufen C , Junru C , Ge L 
Published: June 2023

Abstract

Study question
What is the impact of the dysfunctional lymphoid cells on the development and progression in infertile women with severe polycystic ovaries syndrome (SPCOS).

Summary answer
The dysfunctional lymphoid cells in immune system was deeply correlated with follicular remodeling, which prompting the progression of SPCOS.

What is known already
PCOS has been confirmed as a low-level chronic inflammation impacting on ovulation and luteinization regulated by a cytokine-mediated inflammatory response orchestrated by lymphocytes, granulocytes, and macrophages. However, the exact relationship between immunologic dysfunction and the pathogenesis of PCOS is still not clarified.

Study design, size, duration
A prospective cohort study including a total of 129 women aged 18 to 35 years were enrolled. PCOS patients with polycystic ovaries (ultrasound measurement of the number of ≥ 80 follicles ≥3 mm in diameter) were referred to SPCOS in this study. Peripheral Blood (PB) were collected to detect the immunological changes by using flow cytometry: CD8+ T cell (CD3+,CD8+); CD4+ T cell (CD3+,CD4+); NK cell (CD45+,CD3-,CD56+); NKT cell (CD45+,CD3+,CD56+); Treg cell (CD4+CD25hi); B cell (CD3-CD19+).

Participants/materials, setting, methods
PB from SPCOS cohort (n = 64) and healthy controls (n = 115) were collected to detect the immunological conditions. Furthermore, the discarded tissues from SPCOS patients (n = 5) who needed to avoid OHSS by surgical ovarian wedge resection and women undergoing fertility preservation procedures (n = 3) were digested to single cell suspension, which were used to outline the ovarian homeostasis changes by using scRNA-seq.

Main results and the role of chance
Peripheral blood NK cells from SPCOS patients were significantly decreased than those from healthy group (10.7% vs. 14.9 ± 6.2%, p = 0.04). Conversely, NKT cells in the PB of the SPCOS women were 11.2% vs. 6.9 ± 3.5% (P = 0.02), while B lymphocytes were 15.6% vs. 12.6 ± 4.2% (P = 0.04), compared to healthy controls. Furthermore, the immune cells and distinct cellular clusters of SPCO were disturbed in severe polycystic ovaries. The CD8+ T cell populations in ovarian of SPCOS group were strongly decreased (32.49% vs.22.35%, p &lt; 0.001) and T cell activation signaling was downregulated by lowly expressed PTPRC, APBB1IP, LCP11 and MX12. Besides, the cytotoxicity-associated genes IFNG and TNF were highly expressed, especially in CD4+ T cells. The chemokines released by activated CD4+ T cells may increase the production and recruitment of CD8+ T cell and induce the compositional and functional alteration of ovarian, thereby prompting the progression of PCOS.

Limitations, reasons for caution
The study group is limited and transcriptome analysis covers much, but not enough. Although suggestive associations between immunological conditions and the severity of PCOS have concluded, additional animal models studies should be conducted to confirm our findings further.

Wider implications of the findings
The expression profiles of lymphoid cells provide deep insight into the molecular mechanisms of PCOS. Signaling receptors and gene data set will aid in future studies on the interorgan communication. It also facilitated discovery of novel biomarker for PCOS diagnosis and new immunological treatment.

Trial registration number
Not applicable