zygote, the blastomeres and polar body continue to be surrounded by the zona pellucida. he zygote undergoes slow cleavage for 3 days while still remaining in the fallopian tube. As the blastomeres continue to divide, a solid mulberry-like ball of cells-the morula-is produced. The morula enters the uterine cavity approximately 3 days after fertilization. Gradual accumulation of luid beween the morula cells leads to formation of the early blastocyst.
As early as 4 to 5 days after fertilization, the 58-cell blastula diferentiates into ive embryo-producing cells-the inner cel mass (see Fig. 5-7). he remaining 53 outer cells, called the trophectoderm, are destined to form trophoblasts (Hertig, 1962).
Interestingly, the 107 -cell blastocyst is found to be no larger than the earlier cleavage stages, despite the accumulated fluid within the blastocyst cavity. At this stage, the eight formative, embryo-producing cells are surrounded by 99 trophoblastic cells. And, the blastocyst is released from the zona pellucida secondary to secretion of specific proteases from the secretoryphase endometrial glands (O'Sullivan, 2002).
Release from the zona pellucida allows blastocyst-produced cytokines and hormones to directly influence endometrial receptivity (Lindhard, 2002). IL-la and IL-lj are secreted by the blastocyst, and these cytokines likely directly influence the endometrium. Embryos also have been shown to secrete hCG, which may influence endometrial receptivity (Licht, 2001; Lobo, 2001). The receptive endometrium is thought to respond by producing leukemia inhibitoY factor (LIF), follistatin, and colony-stimulating factor-l (CSF-l). LIF and follistatin activate signaling pathways that collectively inhibit proliferation and promote diferentiation of the endometrial epithelia and stroma to enable uterine receptivity (Rosario, 20 16b). At the maternal-fetal interface, CSF-1 has proposed immunomodulatory actions and pro angiogenic actions that are required for implantation (Rahmati, 2015).
Six or 7 days after fertilization, the blastocyst implants into the uterine wall. This process can be divided into three phases: (1) apposition-initial contact of the blastocyst to the uterine wall; (2) adhesion-increased physical contact between the blastocyst and decidua; and (3) invasion-penetration and invasion of syncytiotrophoblast and cytotrophoblasts into the decidua, inner third of the myometrium, and uterine vasculature.
Successful implantation requires a receptive endometrium appropriately primed with estrogen and progesterone by the corpus luteum. Such uterine receptivity is limited to days 20 to 24 of the cycle. Adherence is mediated by cell-surface receptors at the implantation site that interact with blastocyst receptors (Carson, 2002; Lessey, 2002; Lindhard, 2002). If the blastocyst approaches the endometrium after cycle day 24, the potential for adhesion is diminished because antiadhesive glycoprotein synthesis prevents receptor interactions (N avot, 1991).
At the time of its interaction with the endometrium, the blastocyst is composed of 100 to 250 cells. The blastocyst loosely adheres to the decidua by apposition. This most commonly occurs on the upper posterior uterine wall. Attachment of the blastocyst trophectoderm to the decidual surface by apposition and adherence appears to be closely regulated by paracrine interactions between these two tissues.