About this Research Topic

Background

The uterus and its mucosa, called endometrium, are immunologically unique in their requirements for tolerance to allogenic sperm and semi-allogenic embryos, yet respond to an array of sexually transmitted pathogens and malignancies. To understand this dichotomy, it is fundamental to study the endometrial cellular microenvironment and find new research strategies.

Embryo implantation is a critical step of early prenatal development to establish pregnancy and placenta formation and support embryonic and fetal growth until birth. Implantation mechanisms consist of fine-coordinated processes during which the endometrium undergoes decidualization. This is characterized by the transformation of the endometrial stromal cells to decidual cells, regulated by hormones and facilitated by local immune cells (mostly uterine NK cells). Both immune and stromal cells have an indisputable role in accepting hemiallogenic embryos. Immune cells may reach 30 to 40% of the total endometrial cell population during early pregnancy and approximately 20-30% of women with recurrent implantation failure, habitual abortions, and preeclampsia show elevated uterine NK cell count suggesting its importance.

Apart from tolerance, another necessary process is an enhancement of decidualization, where a recently described interstitial cell population – telocytes - has possibly a tremendous impact. Cellular events during implantation are an enigma for embryologists because of their inaccessibility for direct research, as they occur inside the uterine cavity.

Treatment of patients with recurrent implantation failure, habitual abortion, and idiopathic infertility remains a challenge in reproductive medicine. The best treatment option is probably an approach based on personalized medicine with standardized endometrial immunologically active and stromal cells, with testing and targeted therapy recommendations. Although there is currently no certain indication of immune therapy’s success, it is undeniable that new speculative yet innovative therapeutic approaches are worth exploring, such as the intrauterine platelet-rich plasma or mesenchymal stem cells application.

Understanding the diverse uterus cell populations' immunological roles in reproduction is essential to comprehending the cellular mechanisms of embryo implantation. Therefore, exploring these processes and their translation into clinical practice could substantially impact the further development of the field of reproductive medicine (improvement of fertility and pregnancy outcomes) and the management of sexually transmitted infections and gynecological malignancies.

The current Research Topic welcomes all types of scholarly work that have the potential to unravel novel aspects and mechanisms underlying the physiological and pathophysiological involvement of active cross-talk between spermatozoa, embryos, and the endometrium before, during, and after implantation. We are interested in including studies that cover all aspects of reproductive immunology, and histology, including electron microscopy, clinical embryology, and tissue engineering. Our effort through the present collection is to increase the understanding of maternal-embryo interactions initiated at implantation, to develop clinical interventions to address the high incidence of implantation failures and miscarriages.

Articles may involve one or more of the following research topics:

• Functional and morphological investigation of the complex process of human embryo implantation and investigating the crosstalk between the developing embryo and the endometrial environment that is established at implantation,

• Histology of human endometrium with a focus on endometrial immune and stromal cells including recently described cell population of telocytes,

• Modeling the process of human implantation in vitro,

• Investigating mechanisms of how immune cells, including uterine NK cells, may contribute to successful implantation and implantation failure,

• State-of-the-art immune therapy of pregnancy-related conditions - development of new therapeutic methods aimed at enhancing the success of human embryo implantation and subsequent placentation.

Different article types are welcome to this collection including Mini-Reviews, Brief Research Reports, and Perspectives. A full list of accepted article types, including descriptions, can be found at this link.

Keywords: Human endometrium, Endometrial immune cells, Endometrial stromal cells, Implantation, Decidualization, Placentation, Recurrent implantation failure and miscarriages

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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