Reproductive function in the female is cyclic. A series of functional interrelationships between the hypothalamus, the anterior pituitary, and the ovaries leads to the monthly rupture of an ovarian follicle and extrusion of an egg (“ovulation”), which is then transported to the fallopian tubes to be fertilized. Should fertilization fail to occur, menstruation ensues within 14 days and the hormonal and morphological events that led to ovulation are repeated. Ovulation occurs around day 14 of the menstrual cycle, followed by fertilization as egg and sperm unite within 24 hours. The first three days of development occur within the fallopian tube. Upon arrival within the uterus the conceptus develops into a blastocyst (Figure 1) and begins to make mRNA for human chorionic gonadotropin (hCG), the first hormone signal from the early embryo. By day 6 after fertilization the blastocyst initiates implantation into the maternal endometrium or uterine lining. Within a few days of fertilization the blastocyst becomes a spherical structure composed of two layers. The outside layer of cells become trophoblasts and the inside of a group of cells called the inner cell mass (Figure 2A) will develop into the fetus and ultimately the baby. In addition to making hCG, the trophoblasts mediate the implantation process by attaching to, and eventually invading into the endometrium (Figure 2B). Once firmly attached to the endometrium the developing conceptus grows and continues to expand into the endometrium. One of the basic paradigms which is established even within the first week of gestation is that the embryonic/fetal cells are always separated from maternal tissues and blood by a layer of cytotrophoblasts (mononuclear trophoblasts) and syncytiotrophoblasts (multinucleated trophoblasts) (Figure 2C-F). This is critical not only for nutrient exchange, but also to protect the developing fetus from maternal immunologic attack (1). Implantation is regulated by a complex interplay between trophoblasts and endometrium. On the one hand trophoblasts have a potent invasive capacity and if allowed to invade unchecked, spread throughout the uterus. The endometrium, on the other hand, controls trophoblast invasion by secreting locally acting factors (i.e. cytokines and protease inhibitors), which modulate trophoblast invasion. Within the placenta the syncytiotrophoblasts generate high levels of hCG which modulates cytotrophoblast differentiation towards a non-invasive hormone secreting villous-type trophoblast. The closer the trophoblasts are to the endometrium the less hCG is made, allowing the trophoblasts to differentiate into anchoring type cells (2). Trophoblasts that leave the placenta and migrate within the endo and myometrium are induced to make proteases and protease inhibitors, to further facilitate trophoblast invasion into the maternal tissues (2). Ultimately, normal implantation and placentation is a balance between regulatory gradients created by both the trophoblasts and the endometrium.

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Biotempt B.V., Koekange
R. Benner (Robbert)
Erasmus University Rotterdam
Erasmus MC: University Medical Center Rotterdam

Khan, N. A. (2010, May 26). Immunoregulatory Properties of Break Down Products of Human Choriogonadotropin. Retrieved from