Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver Aurora, CO 80045, USA
*Corresponding author:
Dr. Anil K. Jain
Department of Pharmaceutical Sciences
School of Pharmacy, University of Colorado Denver Aurora
CO 80045, USA Email: anil.jain@ucdenver.edu
Received February 20, 2012; Accepted February 20, 2012; Published February
24, 2012
Citation: Jain AK (2012) Insight from Mechanisms Involved in Uterine Receptivity
for Blastocyst Implantation in Mouse. Anatom Physiol 2:e116. doi:10.4172/2161-0940.1000e116
Human reproduction is a very complex process and now a days
it is not very efficient because of various environmental chemicals,
smoking and diet factors affecting the fertility [1]. Early pregnancy loss
in humans often occurs due to defects before, during or immediately
after implantation, is a worldwide social and economic concern.
In majority of cases, spontaneous abortion occur at the time of
blastocyst implantation due to inappropriate uterine environment
results diminished uterine receptivity or delayed implantation [2]. This
unwanted failure of pregnancy causes emotional and psychological
stress in women which emerges another clinical problem-the problem
of infertility. Many underlying causes of human infertility have been
overcome by in vitro fertilization and embryo transfer technique. The
ultimate goal of understanding implantation at a molecular level is to
improve the diagnosis and treatment of infertility.
Normal fertility involves production and maturation of male
and female germ cells by the gonads, fertilization of the oocyte by
spermatozoa and implantation in the uterus. The implantation of the
healthy blastocyst into the maternal receptive uterus is a very crucial
step in mammalian reproduction for successful pregnancy and it
involves an intricate succession of genetic and cellular interactions,
all of which must be executed within an optimal time frame. The
fertilized egg undergoes specific cell divisions to form a blastocyst.
These developmental events are synchronized with the proliferation
and differentiation of specific uterine cell types, primarily under the
direction of ovarian hormone like Progesterone (P4) and Estrogen
(E2). These hormones make the uterus conductive (receptive) to accept
a blastocyst for implantation. A reciprocal interaction between the
blastocyst and receptive uterus is essential for blastocyst implantation.
Window of Implantation
Successful implantation is the end result of complex molecular
interactions between the hormonally primed uterus and activated
blastocyst. Synchronized development of the embryo to blastocyst stage
and differentiation of the uterus to the receptive state are essential to
this process [3]. Therefore successful implantation is depended on the
following two factors: 1) blastocyst activation and 2) receptivity of the
uterus.
Blastocyst activation: For successful implantation to occur in
the receptive uterus, the blastocyst must also attain implantation
competency, a process termed blastocyst activation. Mechanism that
enables the blastocyst to activate includes catecholestrogens, a class of
estrogen metabolite, which is produced from primary estrogen in the
uterus [4-5]. Blastocyst activation by catecholestrogen involves COX2
derived prostaglandins (PGs) and cAMP [4]. Another lipid signaling
molecule that target blastocyst is an endocannbinoid ananadamide
which activates G-Protein coupled cannabinoid receptors CB1 and
CB2.
Receptivity of the uterus: Uterine receptivity is defined as the
state during the period when the uterine environment is conductive
to support blastocyst growth, attachment and subsequent events of
implantation [6-8]. In humans, the window of uterine receptivity is
considered to be between cycle days 20 and 24 [9]. In the rat and mouse,
uterine receptivity occurs only for a limited period during pregnancy
or pseudo pregnancy. In these species, uterine receptivity divided into
neutral, receptive and non-receptive or refractory phase [7,10-11]. The
uterus becomes receptive only on D4 and becomes refractory on D5.
The neutral phase is achieved when the uterus is exposed to P4 only.
Molecular signals that render the uterus receptive and orders the twoway
interactions between blastocyst and uterus to initiate the process
of implantation still remain ill defined. However a numerous molecules
including growth factors, cytokines, prostaglandins (PGs) mainly
PGE2 and PGI2, histamine, platelet activating factor and various other
molecules have been implicated in this process [8,12-13]. Latest report
suggest the important role of Kruppel like- factor 5 (KLF5), a zinc
factor containing transcription factor and Msx1/Msx2 genes which play
critical role in uterine receptivity and blastocyst implantation [14-15].
Still there is a need to better understand about the molecular
mechanism involved in blastocyst implantation and uterine receptivity
which will be helpful to improve pregnancy rates in women via
development of new drugs to treat infertility with impaired uterine
receptivity.
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