Uterus and cervix histology
Uterus, cervix and vagina histology: the endometrial cycle, transformation zone and vaginal epithelium
The endometrium is a hormone-driven tissue whose glands and stroma change in a predictable way through the cycle, so a biopsy can show whether ovulation has happened. The cervix is mainly collagen lined by two epithelia that meet at a moving junction where almost all cervical cancer starts. The vagina is a glandless, glycogen-rich squamous tube kept acidic by lactobacilli.
Layers of the uterus
- Endometrium: simple columnar epithelium (ciliated and secretory cells), tubular glands and a cellular stroma. Two zones:
- Stratum functionalis: the upper part, supplied by spiral arteries, shed at menstruation and after delivery.
- Stratum basalis: the deep part, supplied by short straight (basal) arteries that do not respond to hormones; it holds the stem cells that rebuild the functionalis. Over-vigorous curettage removes it, giving intrauterine adhesions (Asherman syndrome) with no bleed even after an oestrogen plus progesterone challenge.
- Myometrium: bundles of smooth muscle; the interlacing middle layer surrounds the vessels so contraction after delivery compresses them, the main natural control of PPH.
- Perimetrium: peritoneum over the body and fundus.
- Vessels: uterine artery, arcuate, radial, then straight and spiral arteries.
The endometrial cycle
| Phase (28-day cycle) | Hormone | Glands | Stroma |
|---|---|---|---|
| Menstrual (days 1–4) | Fall of progesterone | Functionalis shed | Collapse, haemorrhage |
| Proliferative (days 5–14) | Oestradiol | Straight, narrow tubular glands, many mitoses | Dense, mitoses |
| Early secretory (days 15–19) | Progesterone | Subnuclear glycogen vacuoles (first sign of ovulation) | Little change |
| Mid secretory (days 20–23) | Progesterone | Secretion in lumens, coiled glands | Oedema; window of implantation |
| Late secretory (days 24–28) | Progesterone falling | Saw-tooth outline | Predecidual cells around spiral arterioles, granular lymphocytes |
- Menstruation: progesterone withdrawal leads to prostaglandin-driven spasm of spiral arteries, ischaemia and shedding of the functionalis.
- A proliferative pattern on day 25 means no ovulation (no corpus luteum, no progesterone). Long unopposed oestrogen causes hyperplasia.
- LNG-IUS: high local progestogen gives small inactive glands in a decidualised stroma, so bleeding is light although ovulation continues.
- Postmenopausal atrophy: few small inactive glands, dense stroma, thin endometrium; the commonest cause of postmenopausal bleeding.
Myometrium in pregnancy
- The uterus grows from about 60 g to about 1000 g, mainly by hypertrophy of muscle cells (stretch and oestrogen), with little increase in cell number. The pregnant breast, in contrast, grows by hyperplasia.
- After delivery the cells shrink by autophagy (involution).
Cervix
- The wall is mostly dense collagen, with only about 10–15% smooth muscle; it is not a muscular sphincter.
- Ripening: collagen breakdown and more hyaluronan and water, driven by prostaglandins, make it soft and distensible before labour.
| Region | Epithelium | Notes |
|---|---|---|
| Endocervix | Simple columnar mucus-secreting | Deep branching crypts; blocked crypts form Nabothian cysts |
| Ectocervix | Non-keratinised stratified squamous, glycogen-rich | Stains brown with Lugol iodine |
- Mucus: oestrogen gives thin, stretchy mucus that ferns; progesterone gives thick, scanty mucus with no ferning (the basis of progestogen-only pill action).
Squamocolumnar junction and transformation zone
- Puberty, pregnancy and the combined pill evert the columnar epithelium onto the ectocervix (ectropion).
- In the acidic vagina the exposed columnar area undergoes squamous metaplasia from bipotential subcolumnar reserve cells. The area between the original and the new junction is the transformation zone, the target of HPV and the site of nearly all CIN and cervical cancer.
- After the menopause the junction recedes into the canal, so colposcopy may be unsatisfactory.
- Lugol (Schiller) test: normal squamous cells store glycogen and stain mahogany brown; CIN lacks glycogen and stays pale (columnar epithelium also stays pale).
- Squamous metaplasia from chronic irritation (for example an IUD) is a classic example of metaplasia.
Vagina
- Non-keratinised stratified squamous epithelium, rich in glycogen under oestrogen; no glands.
- Lamina propria with elastic fibres and a dense venous plexus; lubrication is a transudate through the wall (Bartholin glands moisten only the vestibule).
- Then smooth muscle and adventitia.
- Lactobacilli convert glycogen to lactic acid, keeping the pH about 3.8–4.5, a defence against infection. Before puberty and after the menopause, low oestrogen gives a thin epithelium and a higher pH (atrophic vaginitis).
Remember Straight glands with mitoses mean oestrogen; vacuoles, secretion and saw-tooth glands mean progesterone and therefore ovulation.
Exam trap The functionalis is shed at menstruation; destroying the basalis causes permanent amenorrhoea.
Exam trap The endocervix is lined by simple columnar epithelium, not stratified squamous; the vagina has no glands.
Test yourself on this topic
5 of the 15 questions in our bank on this topic. Choose an answer to see why every option is right or wrong.
The non-pregnant uterus weighs about 60 g, but at term it weighs about 1000 g. Histology of the term myometrium shows smooth muscle cells up to ten times longer than in the non-pregnant state, with little increase in cell number. What is the main process behind the uterine enlargement?
Answer: Hypertrophy of muscle cells
Uterine growth in pregnancy is mainly hypertrophy: existing smooth muscle cells enlarge greatly in length and width, driven by oestrogen and by stretch from the growing conceptus. Some hyperplasia occurs early in pregnancy, but it is a minor part. Connective tissue and vessels also increase. After delivery the cells shrink back by autophagy during involution, without large-scale cell loss.
Uterus in pregnancy
- 60 g to about 1000 g
- Mainly hypertrophy
- Driven by oestrogen and stretch
- Involution by autophagy
Remember Pregnant uterus: bigger cells, not many more.
Exam trap The gravid uterus is the textbook example of physiological hypertrophy, while the pregnant breast is hyperplasia.
Why the other options are wrong
- Hyperplasia of muscle cells Contributes only a little, mostly early in pregnancy.
- Oedema of the myometrium Not the main cause of the weight gain.
- Metaplasia of stromal cells Smooth muscle does not arise from metaplasia here.
- Fibrous tissue deposition Connective tissue rises but is not the main change.
On day 22 of her cycle, a woman's cervical mucus is scanty, thick and sticky; it does not stretch and shows no ferning when dried on a slide. Which hormone has produced this change in the endocervical secretion?
Answer: Progesterone from the corpus luteum
The endocervix is lined by tall mucus-secreting columnar cells in branching crypts. Before ovulation, rising oestrogen makes the mucus abundant, thin, clear and stretchy (spinnbarkeit) with ferning from its salt content, helping sperm pass. After ovulation, progesterone makes it scanty, thick and impenetrable with no ferning. This change is a sign that ovulation has happened and underlies progestogen-only contraception.
Cervical mucus
- Oestrogen: thin, stretchy, ferns
- Progesterone: thick, scanty, no fern
- Made by endocervical columnar cells
- Basis of POP contraception
Remember Ferning means oestrogen; no ferning means progesterone.
Exam trap Ferning reflects oestrogen; its loss after mid-cycle is indirect evidence of ovulation.
Why the other options are wrong
- Oestradiol from the dominant follicle Makes mucus thin, stretchy and ferning.
- LH from the anterior pituitary Acts on the ovary; mucus responds to steroids.
- Prolactin from the anterior pituitary No direct effect on cervical mucus.
- Androgens from the theca interna Not the main control of cervical mucus.
An endometrial biopsy taken on day 9 of a 28-day cycle shows straight, narrow tubular glands with frequent mitoses in both glands and stroma. Which hormone is driving this growth?
Answer: Oestradiol
This is proliferative-phase endometrium. Oestradiol from the growing dominant follicle stimulates regeneration of the functional layer from the basalis, with mitoses in gland cells and stroma and straight, narrow glands. Oestrogen also induces progesterone receptors so the endometrium can respond after ovulation. Progesterone, from the corpus luteum, stops proliferation and starts secretory change.
Proliferative phase
- Days 5–14
- Straight narrow glands
- Many mitoses
- Driven by oestradiol
Remember Mitoses and straight glands = oestrogen.
Exam trap FSH and LH act on the ovary; the endometrium responds to ovarian steroids.
Why the other options are wrong
- Progesterone Causes secretory change and stops mitoses.
- Luteinising hormone Acts on the ovary, not directly on the endometrium.
- Prolactin Has no role in endometrial proliferation.
- Inhibin A Feeds back on FSH; no endometrial action.
Histology of the vaginal wall shows non-keratinised stratified squamous epithelium resting on a lamina propria with a dense venous plexus, but no glands at all. During sexual arousal the vaginal surface becomes moist. Where does most of this fluid come from?
Answer: Transudate through the vaginal wall
The vagina has no glands. During arousal, engorgement of the vascular plexus in the lamina propria increases capillary filtration, and fluid passes between the epithelial cells onto the surface as a transudate. Cervical mucus adds a little at rest, and the Bartholin glands moisten only the vestibule. Oestrogen deficiency thins the epithelium and reduces blood flow, causing dryness after menopause.
Vaginal epithelium
- Non-keratinised stratified squamous
- No glands
- Rich venous plexus in lamina propria
- Lubrication = transudate
Remember The vagina sweats; it has no glands.
Exam trap Do not credit Bartholin glands with vaginal lubrication; they act only at the vestibule.
Why the other options are wrong
- Glands in the vaginal mucosa The vaginal wall contains no glands.
- Bartholin glands at the introitus Moisten only the vestibule, a small volume.
- Endocervical mucus glands Contribute at rest but not the arousal fluid.
- Skene paraurethral glands Small glands near the urethral meatus only.
An endometrial sample shows tortuous glands with a saw-tooth outline and secretions in their lumens. Stromal cells around the spiral arterioles are enlarged with abundant pink cytoplasm, and scattered leucocytes are present. Which phase of the cycle is this?
Answer: Late secretory phase
Late secretory endometrium (about days 24–28) shows exhausted, saw-toothed glands with luminal secretion, predecidual change of stromal cells beginning around spiral arterioles, and infiltrating granular lymphocytes. Early secretory endometrium is identified by subnuclear glycogen vacuoles in gland cells. Proliferative endometrium has straight glands with mitoses, and menstrual endometrium shows breakdown with haemorrhage and stromal collapse.
Late secretory phase
- Saw-tooth glands
- Predecidual stromal cells
- Around spiral arterioles
- Granular lymphocytes appear
Remember Saw-tooth glands plus predecidua = late secretory.
Exam trap Subnuclear vacuoles date the early secretory phase; by the late phase they have gone.
Why the other options are wrong
- Early secretory phase Marked by subnuclear glycogen vacuoles, not saw-tooth glands.
- Mid proliferative phase Straight glands with mitoses.
- Menstrual phase Shows stromal breakdown and blood.
- Late proliferative phase Glands become slightly wavy but still mitotic, no predecidua.
Where this sits in the CPSP syllabus
- Obstetrics & Gynaecology, Paper 2: Histology, Uterus, cervix and vagina: endometrial cycle, transformation zone, vaginal epithelium