Understanding the natural selection of human embryos: Blastocyst quality modulates the inflammatory response during the peri‐implantation period

Abstract

Problem Decidualized cells display an active role during embryo implantation sensing blastocyst quality, allowing the implantation of normal developed blastocysts and preventing the invasion of impaired developed ones. Here, we characterized the immune microenvironment generated by decidualized cells in response to soluble factors secreted by blastocysts that shape the receptive milieu. Method of Study We used an in vitro model of decidualization based on the Human Endometrial Stromal Cells line (HESC) differentiated with medroxiprogesterone and dibutyryl‐cAMP, then treated with human blastocysts‐conditioned media (BCM) classified according to their quality. Results Decidualized cells treated with BCM from impaired developed blastocysts increased IL‐1β production. Next, we evaluated the ability of decidualized cells to modulate other mediators associated with menstruation as chemokines. Decidualized cells responded to stimulation with BCM from impaired developed blastocysts increasing CXCL12 expression and CXCL8 secretion. The modulation of these markers was associated with the recruitment and activation of neutrophils, while regulatory T cells recruitment was restrained. These changes were not observed in the presence of BCM from normal developed blastocysts. Conclusion Soluble factors released by impaired developed blastocysts induce an exacerbated inflammatory response associated with neutrophils recruitment and activation, providing new clues to understand the molecular basis of the embryo‐endometrial dialogue.

Molecular regulators of human blastocyst development and hatching: Their significance in implantation and pregnancy outcome

“…A successful establishment of early pregnancy is absolutely dependent on biologically viable blastocyst having competence to undergo hatching and implantation into the receptive uterine endometrium. 8,10 Blastocyst hatching and implantation events are two sequential, critically linked and rate-limiting events for a prospective pregnancy. The failure of blastocyst hatching leads to implantation failure or early pregnancy loss and infertility.…”

“…2,11 The development of blastocyst, is a series of well-orchestrated event, occurring before the process of implantation. 8,12,13 In the human, spontaneous hatching of blastocysts occur in vivo on day 6 or 7, post-fertilization (dpf) and in in vitro on day 5 dpf. 12,14,15 Prior to implantation, the blastocyst must hatch out of its acellular glycoprotein coat viz., the zona pellucida (ZP or zona).…”

“…A well-balanced immunological interaction and the immunological protection of blastocysts during implantation play key roles from potential attacks by the maternal immune system. [7][8][9] Despite decades of research, the complex processes of human blastocyst development, its hatching and implantation are not fully understood. [7][8][9] Collectively, the blastocyst hatching-implantation failures contribute to the major cause for early pregnancy loss and infertility.…”

“…[7][8][9] Despite decades of research, the complex processes of human blastocyst development, its hatching and implantation are not fully understood. [7][8][9] Collectively, the blastocyst hatching-implantation failures contribute to the major cause for early pregnancy loss and infertility. Understanding the current status of molecular regulators of human blastocyst development, hatching and implantation is of great importance in terms of unravelling the molecular mechanism underlying these events and to diagnose causes of infertility and potentially evolve infertility treatment strategies.…”

The risk of intrauterine exposure to SARS‐CoV‐2 in female COVID‐19 patients: A comprehensive review

“… 13 , 14 , 15 In addition, abnormal hormone and inflammatory environments may disturb the dialog of immune‐endocrine interaction between the decidua and trophoblast during embryo implantation, leading to pregnancy complications. 16 , 17 , 18 , 19 …”