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Implantation

Cyclic hormonal alterations of the endometrium

Over the whole sexually active time span (from puberty to the menopause) the endometrium is subject to cyclic changes  under the influence of the same hormones that regulate ovulation. There are three levels of this hormonal regulation: hypothalamus-pituitary-ovary and it takes place via longer and shorter feedback mechanisms.

The menstruation phase

The menstruation phase (1rst to the 4th day) distinguishes the beginning of each menstruation cycle. When an implantation does not occur, the back-formation of the yellow body (corpus luteum) lowers the amounts of circulating estradiol and progesterone hormones, which leads to the expulsion of the functional layer of the endometrium.

Fig. 4 - Endometrium in the menstruation phase
media/module6/g1b_desquam.gif

A
Functional layer
B
Basal layer
C
Myometrium
1
Uterine cavity with epithelial cells, blood corpuscles and remainders of the expulsed mucosa
2
Intact and partially expulsed uterine glands

Fig. 5 - Enlargement
 
media/module6/g1bv_desquam.gif

3
Intact epithelial cells
4
Basal membrane
5
Uterine stroma
6
Blood corpuscles
7
Free cells of the connective tissue

Legend
Fig. 4, 5

Expulsion of the functional layer of the endometrium (spongiosa and compacta) mixed with blood, endometrial debris and lymphocytes

Fig. 5
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Vascular mechanisms basic to menstruation
The mechanisms that regulate the menstruation phase (1rst-4th day) result from the reduction in the estrogen and progesterone values, leading to a constriction of spiral arteries and consequent necrosis of the tissue.
Only the functional layer of the endometrium is affected by these cyclic changes - the basal layer remains intact.
The uterine vessel network (scheme) exhibits a selective sensibility with regard to the cyclic hormonal alterations. The radial and basal arterioles do not react to the hormonal variations, whereas the spiral arteries of the functional layer are hormone sensitive and constrict when the progesterone concentration decreases.
The cramp-like contractions of the tunica media of the spiral arteries is responsible for an interruption of the blood supply (ischemia), which results in the dying out of the functional layer of the endometrium. Together with blood, which does not coagulate due to a local fibrinolytic factor, the necrotic tissue is eliminated (menstruation).

The follicular or proliferative phase

During the proliferative or follicular phase (4th to 14th day) the secretion of estrogen through the growing ovarian follicle is responsible for the proliferation of the endometrium (intensive mitosis in the glandular epithelium and in the stroma).
The uterus epithelium clothes the surface again. In this stage a certain number of epithelial cells equipped with cilia can be recognized.
The glands grow longer and the spiral arteries wind themselves lightly into the stroma. At the end of the proliferative phase the estradiol peak (released by the growing follicles) triggers a positive feedback mechanism at the level of the pituitary and the ovulation commences 35 to 44 hours after the initial LH increase (modifications hormonales cycliques).

Fig. 6 - Endometrium in the early proliferative phase
media/module6/g1c_prolifprec.gif

  1. Glandular epithelium
  2. Endometrium that is a little developed
  3. Uterine glands
  4. Myometrium

Fig. 7 - Uterine glands
 
media/module6/g1cv_prolifprec.gif

5
Stroma de l'endomètre
6
Cellules épithéliales des glandes utérines

Legend
Fig. 6, 7

Early proliferative phase, characterized by a thin, relatively uniform endometrium.

Fig. 7
 
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Histology in slight and increased enlargement

 

Fig. 8 - Endometrium in the late
proliferative phase
media/module6/g1d_proliftard.gif

  1. Glandular epithelium
  2. Endometrium during the proliferation
  3. Uterine glands
  4. Myometrium

Fig. 9 - Uterine glands
 
media/module6/g1dv_proliftard.gif

5
Stroma of the endometrium (mitosis)
6
Epithelial uterine gland cells with mitotic figures

Legend
Fig. 8, 9

Late proliferative phase:
thickened endometrium with an increased number of glands and mitosis, visible in the glandular epithelium and stroma.

Fig. 9

 

The luteinizing or secretory phase

During the secretory or luteinizing phase (14th to 28th day) the endometrium differentiates itself due to the influence of progesterone (from the corpus luteum) and attains its full maturity. The glands and arteries begin to entwine. The connective tissue stroma becomes the place of edematous changes.
The time period of the maximal reception ability for the blastocyst lies between the 20th and the 23rd day. This phase of the endometrium lasts 4 days and is usually termed the «implantation window».

Fig. 10 - Endometrium in the early secretory phase
media/module6/g1e_secretprec.gif

  1. Glandular epithelium
  2. Thickened endometrium
  3. Uterine glands, curled
  4. Myometrium

Fig. 11 - Uterine glands
 
media/module6/g1ev_secretprec.gif

5
Stroma of the endometrium
6
Epithelial cells of the uterine glands with glycogen collections at the apical pole

Legend
Fig. 10, 11

Early secretory phase:
the endometrium nears its full maturity. The nuclei of the epithelial cells are round and, due to the important production and storage of glycogen at the basal pole, lie at the apical pole near the lumen.

Fig. 11
 
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Histology slight and increased enlargement


Fig. 12 - Endometrium in the
middle secretory phase
media/module6/g1f_secrettard.gif

1
Glandular epithelium
2a
Stratum compactum
2b
Stratum spongiosum
2c
Stratum basale
3
Curled uterine glands
4
Myometrium

Fig. 13 - Uterine glands
 
media/module6/g1fv_secrettard.gif

5
Stroma of the endometrium
6
Epithelial cells of the uterine glands with glycogen collections at the apical pole

Legend
Fig. 12, 13

Middle secretory phase:
The endometrium is now mature; the glycogen migrates from the basal to the apical pole, whereby the nuclei of the epithelial cells are shifted to the basal pole.
The secretion containing glycogen is released into the glandular lumen.

NB: 2a + 2b = Stratum functionale

Fig. 13