Implantation and Maternal Recognition of Pregnancy
There is a huge difference in implantation between species
Key stages in the establishment of pregnancy:
o Pre-implantation development
o Implantation
o Signalling embryo’s presence
o Maternal recognition of pregnancy (foetal allograft)
Blastocyst in free living phase
o Free living refers to the time when a blastocyst isn’t attached to the uterine
wall
During this time the blastocyst is moved along the oviducts by cilia
o The length of time a blastocyst is free living differs between species
Short lived free phase in humans and rodents (4-6 days)
Longer free phase in animals such as sheep (16 days)
Giant pandas can have free living phases of months
Maintenance of blastocyst and embryo
o Histiotrophic nutrition- material is secreted into the uterine lumen by
endometrium and transferred to the trophectoderm
Glands make this nutrition whilst the blastocyst is free living
o Once the blastocyst implants, it is supplied by haemotrophic nutrition
Requires establishment of adjacent maternal and foetal circulations in
placenta for efficient transfer
Transfer occurs in multiple ways:
Diffusion (Oxygen, Carbon dioxide and urea)
Endocytosis fluid uptake (large molecules such as antibodies)
Carrier based mechanisms
o Facilitated diffusion (e.g. glucose)
o Active transport against gradient (e.g. Na/K ATPase)
Blastocyst uterus dialogue
o Timing is important in the endometrium
Breaking up the timing of development gives us a contraceptive
o Implantation window
Pre-receptive period- In first few days the endometrium forms a lining
over itself so that a blastocyst can’t implant
Coat is made of mucin (MUC-1) and has long microvilli on top with
a high surface charge
Receptive period- mucin coat thins, microvilli shorten and low surface
charge
There are integrin-extracellular matrix interactions
, Refractory period- blastocyst is too late and endometrium is resistant to
implantation
If the blastocyst implants, it will be shed with the uterine lining
Implantation stages
o Apposition- particularly important for polytoccus species
Ensures spacing between embryos
Mouse embryos are perfectly spaced with half on one side of the uterine
wall and half on the other side of the wall
o Adhesion
Epithelial cells can be grown on culture plates
Blastocysts can be introduced, and it is possible to look at the
interactions to learn more about adhesion
o Implantation- complex and poorly understood in humans
o Invasion- occurs to a range of degrees
o
Molecules involved in implantation
o Attachment is mediated by multiple molecules:
Tethering by carbohydrate-lectin binding
Lectin is found on the endometrium
Heparin binding EGF-like growth factor with trophoblast expressing EGF
and heparin sulphate proteoglycans
EGF like growth factor is found on the endometrium
This binding stimulates invasion
Integrins- bind to ECM components
o Endometrium and blastocyst must be perfectly expressing these things for
adhesion
Leukaemia inhibitory factor (LIF)
o Spikes at day 4 (when implantation occurs) in mice
This spike doesn’t occur in other animals
o If LIF is knocked out in mice, the blastocyst doesn’t implant
There is a huge difference in implantation between species
Key stages in the establishment of pregnancy:
o Pre-implantation development
o Implantation
o Signalling embryo’s presence
o Maternal recognition of pregnancy (foetal allograft)
Blastocyst in free living phase
o Free living refers to the time when a blastocyst isn’t attached to the uterine
wall
During this time the blastocyst is moved along the oviducts by cilia
o The length of time a blastocyst is free living differs between species
Short lived free phase in humans and rodents (4-6 days)
Longer free phase in animals such as sheep (16 days)
Giant pandas can have free living phases of months
Maintenance of blastocyst and embryo
o Histiotrophic nutrition- material is secreted into the uterine lumen by
endometrium and transferred to the trophectoderm
Glands make this nutrition whilst the blastocyst is free living
o Once the blastocyst implants, it is supplied by haemotrophic nutrition
Requires establishment of adjacent maternal and foetal circulations in
placenta for efficient transfer
Transfer occurs in multiple ways:
Diffusion (Oxygen, Carbon dioxide and urea)
Endocytosis fluid uptake (large molecules such as antibodies)
Carrier based mechanisms
o Facilitated diffusion (e.g. glucose)
o Active transport against gradient (e.g. Na/K ATPase)
Blastocyst uterus dialogue
o Timing is important in the endometrium
Breaking up the timing of development gives us a contraceptive
o Implantation window
Pre-receptive period- In first few days the endometrium forms a lining
over itself so that a blastocyst can’t implant
Coat is made of mucin (MUC-1) and has long microvilli on top with
a high surface charge
Receptive period- mucin coat thins, microvilli shorten and low surface
charge
There are integrin-extracellular matrix interactions
, Refractory period- blastocyst is too late and endometrium is resistant to
implantation
If the blastocyst implants, it will be shed with the uterine lining
Implantation stages
o Apposition- particularly important for polytoccus species
Ensures spacing between embryos
Mouse embryos are perfectly spaced with half on one side of the uterine
wall and half on the other side of the wall
o Adhesion
Epithelial cells can be grown on culture plates
Blastocysts can be introduced, and it is possible to look at the
interactions to learn more about adhesion
o Implantation- complex and poorly understood in humans
o Invasion- occurs to a range of degrees
o
Molecules involved in implantation
o Attachment is mediated by multiple molecules:
Tethering by carbohydrate-lectin binding
Lectin is found on the endometrium
Heparin binding EGF-like growth factor with trophoblast expressing EGF
and heparin sulphate proteoglycans
EGF like growth factor is found on the endometrium
This binding stimulates invasion
Integrins- bind to ECM components
o Endometrium and blastocyst must be perfectly expressing these things for
adhesion
Leukaemia inhibitory factor (LIF)
o Spikes at day 4 (when implantation occurs) in mice
This spike doesn’t occur in other animals
o If LIF is knocked out in mice, the blastocyst doesn’t implant
