Investigating the role of sex hormone-immune interactions in reproductive success
(2025) BINP52 20242Degree Projects in Bioinformatics
- Abstract
- Sex hormones play an important role in shaping immune responses, which in turn influence reproductive outcomes. The molecular and cellular mechanisms underlying the crosstalk between the immune system, sex hormones, and the reproductive system remain poorly understood. This study addressed this knowledge gap by utilizing single-cell RNA sequencing and proteome analysis to enhance the understanding of this crosstalk at a systems-level, exploring how sex hormones influence immune cell function and examining the role of immunity in reproductive success. Systems immunology approaches integrating computational techniques were employed to perform sex hormone receptor expression profiling on immune cells in peripheral blood mononuclear cells... (More)
- Sex hormones play an important role in shaping immune responses, which in turn influence reproductive outcomes. The molecular and cellular mechanisms underlying the crosstalk between the immune system, sex hormones, and the reproductive system remain poorly understood. This study addressed this knowledge gap by utilizing single-cell RNA sequencing and proteome analysis to enhance the understanding of this crosstalk at a systems-level, exploring how sex hormones influence immune cell function and examining the role of immunity in reproductive success. Systems immunology approaches integrating computational techniques were employed to perform sex hormone receptor expression profiling on immune cells in peripheral blood mononuclear cells (PBMC) from healthy females and in menstrual effluent to characterize systemic and local endometrial immunity. Differential expression analysis and gene set enrichment analysis (GSEA) were conducted to identify transcriptional changes associated with sex hormone receptor expression. Consistent with established sexual dimorphism, females exhibited higher proportions of effector memory CD4+ T cells and B cells. Sex hormone receptor profiling revealed ESR2 predominance in B cells across both systemic and endometrial compartments, with GPER1 expression in B cells and CD16+ monocytes, and higher androgen receptor expression in plasmacytoid dendritic cells. GSEA demonstrated that ESR1 positive cells in peripheral blood were enriched for proliferative pathways, while ESR2 positive cells showed enrichment for neutrophil and NK cell-related modules. GPER1 positive cells exhibited reduced classical B cell identity signatures, and AR positive cells showed immunosuppressive profiles. In the endometrial environment, hormone receptor expression correlated with distinct functional transcriptional pathways, with ESR1 and GPER1 expression in macrophages associated with reduced inflammatory gene expression, and progesterone receptor positive uterine NK cells showing reduced antigen presentation pathways. Furthermore, immune proteomic profiling of serum and follicular fluid samples from women undergoing in vitro fertilization (IVF) was performed to assess the relationship between immune profiles and reproductive outcomes. Proteomic analysis of IVF samples revealed immune heterogeneity in recurrent implantation failure (RIF) patients, with elevated proinflammatory cytokines in the follicular fluid and disrupted cytokine co-regulation networks. Follicular fluid IL-13 levels and maternal age were identified as significant negative predictors of pregnancy outcome. This study demonstrates that sex hormone receptor expression shapes immune cell function through distinct transcriptional changes in both systemic and tissue-specific environments, with coordinated regulation between circulating and endometrial immune responses which are essential for shaping reproductive outcomes. Disruptions to these immune networks, characterized by dysregulated cytokine signaling and loss of coordinated immune communication, can contribute to implantation failure, providing critical insights into the molecular mechanisms underlying immune-reproductive crosstalk and highlighting potential therapeutic targets for improving pregnancy outcomes. (Less)
- Popular Abstract
- The immune system does more than just defend against infections, it plays an important role in reproduction. Growing research highlights how sex hormones like oestrogen, progesterone, and testosterone influence immune cell function, yet the precise mechanisms governing their interactions, especially in context of reproductive success, remain largely unexplored.
To investigate this complex relationship, we used advanced techniques such as single-cell RNA sequencing analysis to examine immune cell responses to sex hormones in both peripheral blood and menstrual effluent. By analyzing samples from healthy women, we established an understanding of immune function influenced by sex hormone signaling. We also performed proteome analysis to... (More) - The immune system does more than just defend against infections, it plays an important role in reproduction. Growing research highlights how sex hormones like oestrogen, progesterone, and testosterone influence immune cell function, yet the precise mechanisms governing their interactions, especially in context of reproductive success, remain largely unexplored.
To investigate this complex relationship, we used advanced techniques such as single-cell RNA sequencing analysis to examine immune cell responses to sex hormones in both peripheral blood and menstrual effluent. By analyzing samples from healthy women, we established an understanding of immune function influenced by sex hormone signaling. We also performed proteome analysis to compare immune profiles between women experiencing recurrent implantation failure and those with successful pregnancies to identify key immunological differences that impact pregnancy outcome.
By understanding the intricate relationship between sex hormones, immune responses, and reproductive success, this research offers new insights into factors that contribute to pregnancy success or failure. Ultimately, these findings could pave the way for treatments to improve assisted reproduction outcomes, offering help to women facing fertility challenges. (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/9212691
- author
- Thimmaraya Reddy, Poojaswini
- supervisor
- organization
- course
- BINP52 20242
- year
- 2025
- type
- H2 - Master's Degree (Two Years)
- subject
- language
- English
- id
- 9212691
- date added to LUP
- 2025-09-18 12:29:07
- date last changed
- 2025-09-18 12:29:07
@misc{9212691,
abstract = {{Sex hormones play an important role in shaping immune responses, which in turn influence reproductive outcomes. The molecular and cellular mechanisms underlying the crosstalk between the immune system, sex hormones, and the reproductive system remain poorly understood. This study addressed this knowledge gap by utilizing single-cell RNA sequencing and proteome analysis to enhance the understanding of this crosstalk at a systems-level, exploring how sex hormones influence immune cell function and examining the role of immunity in reproductive success. Systems immunology approaches integrating computational techniques were employed to perform sex hormone receptor expression profiling on immune cells in peripheral blood mononuclear cells (PBMC) from healthy females and in menstrual effluent to characterize systemic and local endometrial immunity. Differential expression analysis and gene set enrichment analysis (GSEA) were conducted to identify transcriptional changes associated with sex hormone receptor expression. Consistent with established sexual dimorphism, females exhibited higher proportions of effector memory CD4+ T cells and B cells. Sex hormone receptor profiling revealed ESR2 predominance in B cells across both systemic and endometrial compartments, with GPER1 expression in B cells and CD16+ monocytes, and higher androgen receptor expression in plasmacytoid dendritic cells. GSEA demonstrated that ESR1 positive cells in peripheral blood were enriched for proliferative pathways, while ESR2 positive cells showed enrichment for neutrophil and NK cell-related modules. GPER1 positive cells exhibited reduced classical B cell identity signatures, and AR positive cells showed immunosuppressive profiles. In the endometrial environment, hormone receptor expression correlated with distinct functional transcriptional pathways, with ESR1 and GPER1 expression in macrophages associated with reduced inflammatory gene expression, and progesterone receptor positive uterine NK cells showing reduced antigen presentation pathways. Furthermore, immune proteomic profiling of serum and follicular fluid samples from women undergoing in vitro fertilization (IVF) was performed to assess the relationship between immune profiles and reproductive outcomes. Proteomic analysis of IVF samples revealed immune heterogeneity in recurrent implantation failure (RIF) patients, with elevated proinflammatory cytokines in the follicular fluid and disrupted cytokine co-regulation networks. Follicular fluid IL-13 levels and maternal age were identified as significant negative predictors of pregnancy outcome. This study demonstrates that sex hormone receptor expression shapes immune cell function through distinct transcriptional changes in both systemic and tissue-specific environments, with coordinated regulation between circulating and endometrial immune responses which are essential for shaping reproductive outcomes. Disruptions to these immune networks, characterized by dysregulated cytokine signaling and loss of coordinated immune communication, can contribute to implantation failure, providing critical insights into the molecular mechanisms underlying immune-reproductive crosstalk and highlighting potential therapeutic targets for improving pregnancy outcomes.}},
author = {{Thimmaraya Reddy, Poojaswini}},
language = {{eng}},
note = {{Student Paper}},
title = {{Investigating the role of sex hormone-immune interactions in reproductive success}},
year = {{2025}},
}