Implantation and Uterus at time of Implantation Lecture – Anatomy Lectures – MBBS Lectures

Specific Learning Objectives

By the end of this session you should be able to:

• Describe how the Implantation begins.
• Describe the structural characteristics of uterus at the time of implantation
• Summarize the phases of menstrual cycle
• Comprehend  the changes in uterus during & after pregnancy

BEGINNING OF IMPLANTATION

• Uterine mucosa or endometrium is in  secretory phase (progesterone from corpus luteum).
• Hence, uterine cavity is full of secretions(rich in nutritive materials) produced by the mucus-producing glands of the endometrium.
• The blastocyst lies free in the uterine secretions for about two days.
• During this period it receives nutrition from the uterine secretions by simple diffusion.
• On the 6th day of development (day 20 of a 28-day menstrual cycle) the zona pellucida disappears by the action of trypsin like enzyme secreted by trophoblastic cells and the conceptus begins to increase rapidly in size.
• Approx. six days after fertilization, blastocyst attaches to the endometrial epithelium.

• Normal site of implantation is the anterior or posterior wall of the upper part of the body of uterus (more frequently on the posterior wall).
• Zona pellucida disappears—– implantation starts.
• The embryonic pole comes in direct contact with the epithelial lining of the endometrium.
• The trophoblast over the embryonic pole starts to proliferate rapidly

• On the 7th day of development irregular processes of cytotrophoblast are seen to invade the simple columnar epithelium of the endometrium.
• L-Selectins (carbohydrate binding proteins) on trophoblast cells & its carbohydrate receptors on uterine epithelium mediate initial attachment of blastocyst to uterus.
• Following capture by selectins, further attachment & invasion by the trophoblast involve integrins by trophoblast & laminin & fibronectin (extracellular matrix molecules) of endometrial epithelium.
• By the end of 1^st wk, blastocyst is superficially implanted in compact layer of endometrium.

Factors causing Implantation Failure

• Altered uterine secretions components
• Altered adhesive molecule profile
• Defective endometrial receptivity/preparation

START OF IMPLANTATION (D 6 – 6 ½)

Interstitial Implantation

Endometrium at implantation (Decidual Reaction):

Due to progesterone of corpus luteum

• Decidual cells formation
  • Endometrial glands enlarge

and tortuous

• Highly vascularized endometrium becomes edematous.

Differentiation of trophoblast
 Syncytiotrophoblast
Invasive (by syncytial microvilli)
Secretes hCG to support. corpus luteum of pregnancy
 Cytotrophoblast
Phases & Mechanism of implantation
 !st Attachment-D6½ L-Selectins on trophoblast cells & its carbohydrate receptors on uterine epithelium & further invasion is due to integrins of trophoblast and laminin & fibronectin in extracellular matrix
 Avoids implantation at opening of uterine gland
Results of implantation:
 Poles are established
 Embryonic pole (site of entry of spermatozoa at fertilization = site of start of implantation = inner cell mass)
 Abembryonic pole
 Dorsal ventral aspects of embryo are established.

IMPLANTATION= DAY—6

UTERUS at time of implantation (Menstrual cycle)

ENDOMETRIUM

Dense CT

Necks of uterine glands

Lacunae & venous spaces

More capillaries

Edematous CT

Dilated & tortuous uterine glands

tortuous arteries

Deep 1/3 of endometrium Coiled & blind ends of uterine glands

straight arteries

Unaffected (menstrual & pregnancy)

Reservoir for regeneration

MENSTRUAL CYCLE

Cyclic or monthly changes in the endometrium  under the influence of estrogen & progesterone

INDUCERS: Ovarian hormones (estrogen & progesterone) and anterior pituitary hormones

• Age of menarche (12-15 years)
• Age of menopause (48-55 years).

PHASES:

1. PROLIFERATIVE OR ESROGENIC OR FOLLICULAR PHASE:
2. It lasts from 5th to 14^th (9 days) day of the cycle.
3. Variable 
4. The epithelium of basal parts of uterine glands of stratum basale regenerates to replace the sloughed endometrium along with proliferation of stroma.

• The uterine glands :
  • increase in number & length.
• The epithelium of glands:
  • becomes rich in glycogen.
• The spiral arteries:
  •  elongate.
• The endometrial thickness:
  • doubled or tripled (2-3 mm thick or more).
• These changes occur due to estrogen of granulosa cells of ripening Graafian follicle under the inductive influence of FSH from anterior hypophysis.

MENSTRUAL CYCLE (continues)

2. SECRETORY OR PROGESTATIONAL OR LUTEAL PHASE:

• Duration:
  • From the ovulation to the onset of next phase of cycle (15^th -26^th  day).
• Marked by:
  •  active phase of uterine glands (secretions).
• The glandular epithelium is:
  •  hypertrophied, tortuous and folded.
•  During the initial secretory phase (15th-21st days), the cells of glands accumulate glycogen in their basal regions
• During the late secretory phase (22nd-26th days) the glands are highly coiled (serrated appearance in sections) and their cells present secretions at their apical regions.

• The lumen of glands is dilated.
• Mitoses are rare.
• The endometrium is further thickened, edematous and congested with blood.
• The spiral arteries extend up to the surface epithelium & become increasingly coiled.
• The stromal cells of endometrium differentiate into decidual cells. These changes occur due to LH from anterior hypophysis as well as progesterone from theca interna of corpus luteum.
• The changes are essential for the implantation of the conceptus, if fertilization takes place.
• Large venous spaces (lacunae) develop & direct arteriovenous anastomoses are prominent feature of this stage. 

Progesterone:

• inhibits the contraction of myometrium, helping in implantation.
• The thickness of endometrium:
  • 4-6 mm.
• During late secretory phase of menstrual cycle and pregnancy:
  • the endometrium becomes divisible into stratum functionalis and stratum basalis.
• If fertilization does not occur:
  • the corpus luteum starts to degenerate, estrogen & progesterone levels fall.

3. On 27th or 28th day of menstrual cycle,

• Ischemic phase (reduced blood supply) or premenstrual phase leading to onset of menstrual phase of next cycle.

• Spiral arteries:
  •  constrict, giving the endometrium a pale appearance.
• Hormonal withdrawal:
  •  results in stoppage of glandular secretion, a loss of interstitial fluid, & a marked shrinkage of endometrium.
• Towards the end of ischemic phase:
  •  spiral arteries become constricted for a longer period resulting in venous stasis & patchy ischemic necrosis (death) in the superficial tissue.
• Rupture of damaged vessel walls follows & blood seeps into surrounding CT.

4.  MENSTRUAL PHASE:

• Apparent by:
  •  menstrual flow (20-80 ml), which lasts for 4-5 days.
• The corpus luteum:
  •  ceases functioning after 14 days.
• The titre of progesterone and estrogens drops.
• At the end of secretory phase (28th day) the walls of coiled arteries contract, leading to ischemia and necrosis of their own walls as well as of zona functionalis of endometrium.
• So the vessels above the constriction rupture leading to bleeding.
• Small pools of blood form & break through endometrium.

• Torn ends of arteries bleed & 20-80 ml blood is lost.
• Over 4-5 days, entire compact & most of spongy layer are discarded in menses.
• The menstrual discharge contains blood, endometrial epithelial cells, sloughed stroma, mucous secretions of uterine and cervical glands and degenerated secondary oocyte.
• If implantation occurs:
  •  then hCG from trophoblast of embryo sustains the corpus luteum and menstruation does not occur.

• At the end of menstrual phase:
  • Endometrium is reduced to 1 mm thickness 
  • contains basal parts of uterine glands and
  •  proximal portions of spiral arteries.

CHANGES IN UTERUS DURING AND AFTER PREGNANCY

DURING PREGNANCY:

• Menstrual cycles cease
• The uterus increases in size enormously to accommodate the developing fetus.
  • The Myometrium grows due to increase in size of individual muscle fibres (from 50 µm to 500 µm thick)  as well as increase in number of smooth muscle cells (hypertrophy and hyperplasia of smooth muscle cells). There is also active synthesis of collagen.
  • The Endometrium also grows enormously.

AFTER DELIVERY, enzymatic changes occur in smooth muscle and collagen leading to their destruction as well as reduction in size.

• This is known as involution (reduction in size of uterus).
• The ovarian & menstrual cycles resume after a variable period of 6-10 weeks if the woman is not breast-feeding her child.

SUMMARY (Ovulation-1^st week-Implantation)

1. Epithelium of the uterine mucosa
2. Hypoblast
3. Syncytiotrophoblast
4. Cytotrophoblas

lFig. 18 – Implantation: 6th-7th day. Free blastocyst (following the dissolution of the pellucid zone) in adplantation phase on the uterine wall (6th to 7th day). The trophoblast cells of the embryonic pole differentiate themselves, multiply, and form the invasive syncytiotrophoblast. The abembryonic pole consists of cytotrophoblast cells.