Hormonal and embryonic regulation of chemokines IL-8, MCP-1 and RANTES in the human endometrium during the window of implantation

Abstract

Chemokines are a family of small polypeptides which specialize in the attraction of leukocytes. The presence of specific leukocyte subsets at the implantation site is an important element of the complex, and not completely understood, process of embryonic implantation. This report includes the investigation of the in-vivo immunolocalization and hormonal regulation of interleukin (IL)-8, monocyte chemotactic protein (MCP)-1 and RANTES (regulated upon activation normal T-cell expressed and secreted) in the human endometrium during hormone replacement therapy cycles for oocyte recipients in an IVF programme. In addition, we have analysed the embryonic regulation of these endometrial epithelial chemokines (IL-8 and MCP-1) using an in-vitro model for the apposition phase of human implantation by co-culturing single human embryos until the blastocyst stage with human endometrial epithelial cells (EEC). IL-8 and MCP-1 were immunolocalized in the human endometrium to the glandular and lumenal epithelium as well as to the endothelial cells. RANTES was mainly localized to the stromal compartment and endothelial cells. The immunoreactive levels of endometrial IL-8 and MCP-1 were up-regulated by the administration of progesterone during the receptive phase of the cycle. Furthermore, it was demonstrated that, in vitro, the human blastocyst does not produce measurable amounts of IL-8, MCP-1 or RANTES; however, it does up-regulate EEC IL-8 mRNA expression (P < 0.05) and protein production (P < 0.05), but not IL-8 secretion. The human embryo did not regulate EEC MCP-1 expression. These results provide evidence of hormonal and embryonic regulation of specific endometrial chemokines, suggesting two different but related mechanisms to induce the production of chemokines by the EEC, thus contributing to the attraction of specific leukocyte populations during the peri-implantation phase.

The UDP-Glucose Receptor P2RY14 Triggers Innate Mucosal Immunity in the Female Reproductive Tract by Inducing IL-8

“…Based on our proposed model, it is conceivable that UDPglucose may be released from these apoptotic endometrial epithelial cells, which, in turn, may activate P2RY14 in a paracrine/ autocrine manner, leading to IL-8 production. Consistent with our hypothesis, Caballero-Campo et al (49) demonstrated using in vitro coculture experiments that both IL-8 mRNA expression and protein production were up-regulated in endometrial epithelial cells in the presence of a human blastocyst. In both menstruation and implantation, IL-8 production and infiltrated neutrophils may play a role in the angiogenesis for endometrial remodeling/regeneration, trophoblast invasion, and placentation, rather than prevention of the progression of infection (50).…”

Bisphenol A modulates receptivity and secretory function of human decidual cells: an in vitro study

“…The proper development of the maternal decidua and the molecular cross-talk between the decidua and the fetal trophoblast are of paramount importance for blastocyst invasion into the endometrium, implantation, and successful pregnancy. The importance of the endometrial stroma in this cross-talk resides in the fact that steroid hormones target endometrial stromal cells, which in turn facilitate the interaction between the blastocyst and the uterine epithelium (Ghosh & Sengupta 1998, Caballero-Campo et al 2002, Bourdiec et al 2013). …”

“…During the window of receptivity, steroid hormones facilitate the interaction between the blastocyst and the uterine epithelium via the endometrial stroma (Ghosh & Sengupta 1998, Caballero-Campo et al 2002, Bourdiec et al 2013. Therefore, an altered pattern of expression of their receptors in the decidua could well have a negative impact on female fertility, especially on the success of implantation.…”

Effects of Secretable Placental Factors Upon Secretion of Cytokines by THP-1 Monocyte-Like Cells

“…Medical Immunology Медицинская Иммунология хемоатрактантом для моноцитов и макрофагов, а также для Т-лимфоцитов и NK-клеток, которые мигрируют в децидуальную ткань матки из пери-ферической крови в течение беременности [5]. Повышенная секреция этого хемокина клетками линии ТНР-1 может свидетельствовать о потен-циальной возможности мигрирующих в деци-дуальную ткань моноцитов, а также макрофагов децидуальной ткани и ткани плаценты секрети-ровать МСР-1 в первом триместре беременности, обеспечивая адекватное аккумулирование клеток иммунной системы матери в децидуальной обо-лочке.…”

“…Гестоз со-провождается нарушением формирования ткани плаценты и усиленной продукцией провоспали-тельных цитокинов [28], способных активировать моноциты и стимулировать усиленную секрецию MCP-1 макрофагами децидуальной оболочки и ткани плаценты. Под действием MCP-1 моно-циты, макрофаги, Т-лимфоциты и NK-клетки матери мигрируют в децидуальную ткань и ткань плаценты [5], усиливая мононуклеарную ин-фильтрацию и способствуя развитию местной воспалительной реакции, характерной для гесто-за. Хотя секреция IL-6 клетками линии ТНР-1 была повышена в присутствии секреторных продуктов ткани плацент женщин с гестозом по сравнению со здоровыми беременными, она оставалась на достаточно низком уровне.…”