At the end of the first week and into the second week the blastocyst initially attaches to the uterine endometrium at a particular site and then begins the process of implantation.
Animation showing the process of blastocyst implantation into the maternal uterus. (More? Week 2 Movies)
Implantation begins first with attachment (adplantation) of the blastocyst through the outer trophopoblast cells to the uterine lining. Following adplantation, trophoblast cells on the outside differentiate into syncitiotrophoblasts which invade the uterine endometrium. The blastocyst then moves moves into the endometrium, initially partially buried, and on completion of implantation, is fully buried in the endometrium. The site of implantation is marked on the surface by a "plug".
There are many different sites of implantation, some of which may not even be within the uterus.
Physically, following attachment, the inner cell mass is usually juxtaposed (beside) the uterine wall with the blastoceal cavity away from the wall.
The uterine wall is hormonally regulated in preparation for implantation (see menstrual cycle notes) and a recent study (Stewart et al., 1992) has also shown that leukaemia inhibitory factor (LIF) secreted by the uterine glands aids in normal blastocyst implantation. This LIF may either act autocrinely on the wall or alter the blastocyst.
Following Implantation the blastocyst secretes human chorionic gonadotrophin (HCG) which maintains the endometrium and therefore no menstruation occurs. The detection of HCG in the urine is the most reliable and basis of nearly all pregnancy tests (More? pregnancy tests).
Grewal S, Carver JG, Ridley AJ, Mardon HJ. Implantation of the human embryo requires Rac1-dependent endometrial stromal cell migration. Proc Natl Acad Sci U S A. 2008 Oct 6.
"we demonstrate in an in vitro model for human implantation that the Rho GTPases Rac1 and RhoA in human endometrial stromal cells modulate invasion of the human embryo through the endometrial stroma."
The Rho GTPases are involved in the reorganisation of the actin cytoskeleton within cells and is required for all cell motility. This PNAS paper shows that endometrial stromal cells also use this signaling pathway to regulate their motility associated with implantation in the second week of human development.
Makrigiannakis A, Minas V. Mechanisms of implantation. Reprod Biomed Online. 2007 Jan;14(1):102-9.
Achache H, Revel A. Endometrial receptivity markers, the journey to successful embryo implantation. Hum Reprod Update. 2006 Nov-Dec;12(6):731-46.
The current commonly available pregnancy tests measure the presence of human chorionic gonadotrophin (HCG) in urine (6-8 days following fertilization) and levels rise to a peak at 7 to 10 weeks. This HCG is produced by initially in week 2 by the syncitiotrophoblasts from the implanting conceptus.
Pregnancy test kits are sensitive to about 25 units/litre using a monoclonal antibody to the beta-subunit of HCG that will recognise both intact HCG (in maternal serum) and with HCG fragments (in maternal urine).
A positive test by the time of the expected period will be 98% correct.
A woman is usually not pregnant with a negative result 1 week after the missed period.
HCG subunits HCGalpha and HCGbeta, partially degraded or nicked forms of HCG and HCGbeta, and the beta-core fragment.
References: Stenman UH, Tiitinen A, Alfthan H, Valmu L. The classification, functions and clinical use of different isoforms of HCG. Hum Reprod Update. 2006 Nov-Dec;12(6):769-84.
Search PubMed: term = pregnancy test | human chorionic gonadotrophin
After implantation cells within the developing placenta (syncitiotrophoblasts) synthesize and secrete Human chorionic gonadotrophin (hCG) into the maternal bloodstream. The main function of serum hCG is to maintain the corpus luteum in the maternal ovary and therefore maintain the early pregnancy, that is block the menstrual cycle.
Weeks after Last Menstrual period (LMP) |
Days after Fertilization |
hCG level for Singleton (mIU/ml or IU/L) |
Week 3 | 7 |
0 to 5 |
Week 4 |
14 (next period due) | 5 to 426 |
Week 5 | 21 | 18 to 7340 |
Week 6 | 28 | 1,080 to 56,500 |
Weeks 7 to 8 | 35 to 42 | 7,650 to 229,000 |
Weeks 9 to 12 | 49 to 70 | 25,700 to 288,000 |
Weeks 13 to 16 | 77 to 100 | 13,300 to 254,000 |
Weeks 17 to 24 | 4,060 to 165,400 | |
Weeks 25 to birth | 3,640 to 117,000 | |
Weeks 4 to 6 neonatal | Less than 5 |
Progesterone is elevated during pregnancy, approximately 10 times higher than non-pregnant circulating levels and continues to increase throughout the pregnancy.
Low maternal serum progesterone levels during the first trimester is associated with, but not the cause of, miscarriage.
High maternal serum progesterone levels are associated with multiple pregnancy (More? Twinning) or hydatidiform mole (More? Hydatidiform Mole)
|
Blastocyst implantation depends on maternal expression of leukaemia inhibitory factor. Stewart CL, Kaspar P, Brunet LJ, Bhatt H, Gadi I, Kontgen F, Abbondanzo SJ Nature 1992 Sep 3;359(6390):76-79
"A critical point during mammalian pregnancy is the implantation of the blastocyst when the embryo attaches to the wall of the uterus. The autonomously developing preimplantation embryo then becomes dependent on the maternal environment for its continued development. Little is known about the regulation of implantation, except that a complex interaction between peptide and steroid hormones synchronizes the preparation of the uterus for implantation with the development of the embryo. Whether the implantation event is under maternal or embryonic control is also unclear (reviewed in refs 1, 2). We have previously shown that a cytokine, leukaemia inhibitory factor (LIF), is expressed in the uterine endometrial glands specifically on the fourth day of pregnancy. This burst of expression is under maternal control and always precedes implantation of the blastocyst. Here we report that transient expression of LIF in mice is essential for implantation. Females lacking a functional LIF gene are fertile, but their blastocysts fail to implant and do not develop. The blastocysts, however, are viable and, when transferred to wild-type pseudopregnant recipients, they can implant and develop to term."
Many of the links below are to external resources and require an internet connection.
Links: Earlier References | Journals | Online Textbooks | Search Textbooks | PubMed | Search PubMed | Books | Glossary
Online Textbooks
Developmental Biology (6th ed) Gilbert, Scott F. Sunderland (MA): Sinauer Associates, Inc.; c2000. Oogenesis in mammals |
Molecular Biology of the Cell (4th Edn) Alberts, Bruce; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keith; Walter, Peter. New York: Garland Publishing; 2002. Integrins Are Transmembrane Heterodimers
Search NLM Online Textbooks- "implantation" : Developmental Biology | The Cell- A molecular Approach | Molecular Biology of the Cell | Endocrinology
Reviews
Makrigiannakis A, Minas V. Mechanisms of implantation. Reprod Biomed Online. 2007 Jan;14(1):102-9.
Achache H, Revel A. Endometrial receptivity markers, the journey to successful embryo implantation. Hum Reprod Update. 2006 Nov-Dec;12(6):731-46.
Articles
Grewal S, Carver JG, Ridley AJ, Mardon HJ. Implantation of the human embryo requires Rac1-dependent endometrial stromal cell migration. Proc Natl Acad Sci U S A. 2008 Oct 6.
Search PubMed
Search May 2007 "blastocyst implantation" 7,075 reference articles of which 958 were reviews.
Search PubMed: term = blastocyst implantation | implantation |
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Week 2 is about blastocyst "hatching", following which a rolling adhesion, adplantation and then implantation can occur, a process unique to placental animals.
I often think that the process resembles that which occurs when a white blood cell rolls, adheres and then migrates through a vessel wall into a tissue.
This page also covers pregnancy detection using the detection of HCG in the maternal urine.
Please email Dr Mark Hill if you wish to make a comment about this current project.