Endometrial Immune Genetics in Assisted Reproduction: The Role of KIR Polymorphisms and HLA Ligand Interactions in Fertility Outcomes
- Autores: Isabel Cuadrado Torroglosa
- Directores de la Tesis: Antonio Pellicer Martínez (codir. tes.), Meda Diana Alecsandru (codir. tes.), Juan Antonio García Velasco (codir. tes.), José Remohí Giménez (tut. tes.)
- Lectura: En la Universitat de València ( España ) en 2026
- Idioma: inglés
- Número de páginas: 306
- Tribunal Calificador de la Tesis: Romina Dieli Crimi (presid.), José Bellver Pradas (secret.), Mauro Cozzolino (voc.)
- Programa de doctorado: Programa de Doctorado en Biomedicina y Biotecnología por la Universitat de València (Estudi General)
- Menciones:
- Internacional
- Calificación: Sobresaliente Cum Laude
- Enlaces
- Resumen
The immune system plays a crucial role in reproduction, modulating implantation, placentation, and the establishment of a healthy pregnancy.
Among the immune cell populations involved, uterine Natural Killer (uNK) cells stand out as the most abundant in the endometrium and decidua. Their functions include regulating trophoblast invasion, remodelling uterine spiral arteries, or protecting against pathogens. The activity of these cells is largely shaped by interactions between their Killer-cell Immunoglogulin-like receptors (KIRs) and the Human Leukocyte Antigen (HLA) ligands expressed by the endometrium and the extravillous trophoblast (EVT), all of which are highly polymorphic. Variability in these interactions, particularly in KIR-HLA-C and KIR-HLA-F combinations, may alter uNK function and ultimately influence reproductive outcomes.This thesis investigates the impact of KIR polymorphisms on reproductive biology by analysing their influence on endometrial gene expression, hormonal profiles, cytokine production, or reactive oxygen species. It also examines reproductive outcomes in oocyte-donation recipients according to KIR-HLA-C combinations and specific HLA-F polymorphisms, with the aim of identifying risk variants. In addition, it explores potential immunomodulatory strategies and the association of KIR genotypes with conditions such as chronic endometritis or endometrial dysbiosis. Together, these approaches seek to deepen current understanding of these receptors, the functional behaviour of uNK cells, and the broader immune contribution to fertility in general and to assisted reproduction in particular.The findings of this work point to a broad involvement of KIR polymorphisms in multiple dimensions of the reproductive process, both individually and in combination with HLAC and HLA-F. The identification of variants associated with differences in implantation, pregnancy loss, or specific endometrial conditions supports the notion that immune communication is essential for maintaining a functional and tolerogenic uterine environment, necessary for a healthy pregnancy. Overall, these results reinforce the relevance of immunogenetics in fertility and highlight the need for increasingly personalised strategies in assisted reproduction
