Ovary and fallopian tube histology
Ovary and fallopian tube histology: follicles, corpus luteum and the tubal lining
The ovary is a cortex full of follicles at different stages around a vascular medulla, and each stage is defined by the cells around the oocyte. Knowing which cell makes which hormone (theca androgen, granulosa oestrogen, luteal progesterone) explains ovulation induction, PCOS and the ovarian tumours. The tube is a ciliated, muscular conduit whose parts behave differently in ectopic pregnancy.
General structure of the ovary
- Surface ("germinal") epithelium: a single layer of cuboidal cells, a modified peritoneal mesothelium. Despite the name it does not produce germ cells; it is the likely source of some surface epithelial tumours.
- Tunica albuginea: dense connective tissue under the surface; thick and white in polycystic ovaries.
- Cortex: follicles in a cellular, spindle-cell stroma. Medulla: loose tissue, large vessels, nerves.
- Hilus cells: Leydig-like cells at the hilum with Reinke crystals; a hilus cell tumour secretes testosterone and virilises an older woman with normal DHEA-S.
Follicle stages
| Stage | Follicular cells | Other features |
|---|---|---|
| Primordial | Single layer of flat cells | Primary oocyte arrested in prophase I; the resting pool in the outer cortex |
| Primary | Cuboidal, one then several layers | Zona pellucida appears (made by oocyte and granulosa) |
| Secondary (preantral to early antral) | Many layers of granulosa | Small fluid spaces appear; theca interna and externa become distinct; Call–Exner bodies |
| Graafian (mature) | Granulosa lining a single large antrum | Oocyte on the cumulus oophorus; about 18–25 mm on ultrasound before ovulation |
- The follicle is named by its follicular cells, not by the oocyte: a primordial follicle already holds a primary oocyte.
- Zona pellucida: acellular glycoprotein (ZP1–3), strongly PAS positive; ZP3 binds sperm and the zona reaction blocks polyspermy.
- Corona radiata: the innermost layer of the cumulus, made of granulosa cells, released with the egg.
- Just before ovulation the LH surge completes meiosis I: a secondary oocyte and the first polar body; the egg then arrests in metaphase II.
Theca and granulosa: the two-cell system
| Layer | Vascularity | Stimulus | Product |
|---|---|---|---|
| Theca interna | Highly vascular | LH | Androgens (androstenedione) from cholesterol |
| Theca externa | Fibromuscular | None specific | Support |
| Membrana granulosa | Avascular until ovulation (behind the basal lamina) | FSH | Aromatase converts theca androgen to oestradiol; inhibin B; AMH |
- Granulosa cells lack 17-alpha-hydroxylase, so they depend on theca androgen.
- Letrozole blocks granulosa aromatase; oestradiol falls, negative feedback lifts, FSH rises and a follicle grows.
- PCOS: high LH drives hyperplastic theca interna and excess androgen; the ovary shows a thick capsule, many subcapsular follicles and no corpora lutea (no ovulation).
- Granulosa cell tumour: a sex cord–stromal tumour with Call–Exner bodies; its oestrogen causes endometrial hyperplasia and postmenopausal bleeding. Sex cords come from coelomic epithelium, unlike the oocyte (germ cell).
Ovulation and the corpus luteum
- After rupture, blood from torn theca vessels fills the cavity: the corpus haemorrhagicum (can bleed into the peritoneum).
- Vessels now invade the granulosa layer, giving the cells cholesterol; this vascular invasion lets the corpus luteum make large amounts of steroid.
| Lutein cell | Appearance | Main product |
|---|---|---|
| Granulosa lutein | Large, pale, lipid-rich, central | Progesterone, oestradiol, inhibin A |
| Theca lutein | Small, dark, at the periphery and in folds | Androgen (precursor for oestradiol) |
- The corpus luteum secretes progesterone, oestradiol and inhibin A, so in the mid-luteal phase FSH is suppressed.
- Without pregnancy it lives about 14 days and regresses to a corpus albicans, a white hyaline collagen scar with few cells.
- In pregnancy hCG from the syncytiotrophoblast binds the LH receptor and prevents luteolysis until the placenta takes over at about 7–10 weeks.
Evidence of ovulation
- Signs that ovulation has occurred: mid-luteal progesterone rise, a sustained basal body temperature rise of about 0.3–0.5 °C, loss of cervical mucus ferning.
- During breastfeeding, prolactin suppresses GnRH pulses, so follicles fail to mature (lactational amenorrhoea).
Fallopian tube
- Wall: mucosa, two-layered muscularis (inner circular, outer longitudinal) and serosa.
- Lining: simple columnar with ciliated cells (beat towards the uterus, more numerous under oestrogen) and secretory (peg) cells that nourish the gamete and embryo.
| Part | Mucosa | Muscle | Clinical point |
|---|---|---|---|
| Infundibulum and fimbriae | Fringed folds | Thin | Pick up the egg; site of STIC, precursor of high-grade serous carcinoma |
| Ampulla | Tall, highly branched folds, wide lumen | Thin | Site of fertilisation; commonest site of ectopic pregnancy |
| Isthmus | Few folds, narrow lumen | Thick | Ectopic here ruptures earliest |
| Intramural | Narrowest lumen | Thick | Interstitial (cornual) ectopic bleeds heavily |
- Primary ciliary dyskinesia (dynein arm defect): patent tubes on HSG but poor transport, so subfertility and ectopic pregnancy.
- In BRCA carriers the fimbriae are the usual origin of serous "ovarian" cancer, so the whole tube is removed and examined.
Remember Theca makes the androgen under LH, granulosa turns it into oestrogen under FSH, and after ovulation the luteinised granulosa makes progesterone.
Exam trap Do not call a follicle primary just because it holds a primary oocyte; every follicle before ovulation holds one, and the name follows the follicular cells.
Exam trap The granulosa layer is avascular before ovulation; bleeding into a ruptured follicle comes from the theca.
Test yourself on this topic
5 of the 23 questions in our bank on this topic. Choose an answer to see why every option is right or wrong.
In a histology session on ovarian follicles, a student notices that a thin glycoprotein layer first appears between the oocyte and its surrounding cells once those cells change from flat to cuboidal. At which stage of follicle development does this layer first appear?
Answer: Primary follicle
The zona pellucida is first laid down in the primary follicle, when the follicular cells become cuboidal and the oocyte enlarges. Both the oocyte and the granulosa cells contribute its glycoproteins (ZP1–ZP3). It thickens as the follicle grows and is present well before the antrum forms. It is absent in the primordial follicle and is shed with the oocyte at ovulation, so the corpus luteum has none.
Zona pellucida timing
- Appears in the primary follicle
- Made by oocyte and granulosa cells
- Glycoproteins ZP1–ZP3
- Leaves with the ovum at ovulation
Remember Cuboidal cells and zona arrive together.
Exam trap The zona is not a product of the corona radiata alone; the oocyte itself secretes much of it.
Why the other options are wrong
- Primordial follicle Has flat cells and no zona yet.
- Antral follicle Zona already present before the antrum.
- Graafian follicle Zona formed long before this stage.
- Corpus luteum Formed after ovulation; zona leaves with the ovum.
A 29-year-old woman with recurrent sinusitis, bronchiectasis and dextrocardia has had an ectopic pregnancy and now has subfertility. Her tubes are patent on HSG. What explains her tubal problem?
Answer: Defective dynein arms of tubal cilia
This is primary ciliary dyskinesia (Kartagener syndrome when situs inversus is present). Mutations affect the dynein arms of the ciliary axoneme, so cilia cannot beat in a coordinated way. Ciliary beating in the tubal epithelium, together with peristalsis, helps move the ovum and early embryo towards the uterus. Slow transport causes subfertility and a raised risk of ectopic implantation, even though the tubes are patent.
Cilia and the tube
- Dynein arm defect
- Cilia cannot beat
- Slow ovum transport
- Subfertility and ectopic risk
Remember Same cilia in airway and tube.
Exam trap A patent tube on HSG does not mean a working tube; transport needs active cilia.
Why the other options are wrong
- Loss of tubal peg cells Secretory cells are not affected by this syndrome.
- Thickened tubal muscle layer Not a feature of this disorder.
- Squamous metaplasia of the tube The tubal lining stays columnar.
- Fibrosis of the fimbriae Patent tubes and the syndrome point away from post-infective damage.
A PAS-stained section through a large ovarian follicle shows a bright magenta, acellular ring immediately around the oocyte. Which structure is this?
Answer: Zona pellucida
The zona pellucida is a thick acellular coat of glycoproteins lying directly on the oocyte membrane. Its carbohydrate content makes it strongly PAS positive. It carries ZP3, the sperm receptor that triggers the acrosome reaction, and hardens after fertilisation to block polyspermy. The corona radiata and cumulus are cellular, and the theca interna is a vascular cellular layer outside the basal lamina.
Zona pellucida
- Acellular glycoprotein coat
- Strongly PAS positive
- ZP3 binds sperm
- Zona reaction blocks polyspermy
Remember PAS-pink ring right on the oocyte = zona.
Exam trap The corona radiata looks ring-like too, but it is made of cells.
Why the other options are wrong
- Corona radiata Cellular layer outside the zona.
- Membrana propria Basal lamina further out, under the theca.
- Theca interna Vascular, cellular steroid-making layer.
- Cumulus oophorus Cellular mound of granulosa cells.
A haemorrhagic corpus luteum is removed at laparoscopy on day 22. Histology shows a folded wall made mostly of large, pale, lipid-rich cells, with smaller darker cells at the periphery and in the folds. The large cells are the main source of which secretion?
Answer: Progesterone
After ovulation the granulosa cells enlarge, fill with lipid and become granulosa lutein cells, which form most of the corpus luteum. They secrete large amounts of progesterone and also oestradiol, as they keep their aromatase. The smaller, darker theca lutein cells at the edges and in the folds come from theca interna and make androgens and some progesterone. Inhibin B and AMH come from granulosa cells of growing follicles, not the luteal gland.
Corpus luteum cells
- Large pale cells = granulosa lutein
- Make progesterone (and oestradiol)
- Small dark cells = theca lutein
- Theca lutein make androgens
Remember Big pale cells, big progesterone output.
Exam trap Granulosa cells of the corpus luteum make inhibin A, while those of growing follicles make inhibin B.
Why the other options are wrong
- Androstenedione Mainly from the small peripheral theca lutein cells.
- Inhibin B Product of growing follicles; the corpus luteum makes inhibin A.
- Anti-Müllerian hormone Made by granulosa of small growing follicles.
- Human chorionic gonadotrophin Made by syncytiotrophoblast, not the ovary.
An ovarian section shows a single layer of cuboidal cells on the surface, then dense connective tissue, then a cortex full of follicles. A student calls the surface layer 'germinal epithelium'. What does this layer actually represent?
Answer: Modified peritoneal mesothelium
The 'germinal epithelium' is a misnomer. It is a simple cuboidal modified mesothelium continuous with the peritoneum at the hilum and does not produce germ cells; oogonia come from primordial germ cells that migrate from the yolk sac wall. Beneath it lies the dense tunica albuginea. This surface layer and its inclusion cysts are a source of epithelial ovarian tumours.
Ovarian surface epithelium
- Simple cuboidal layer
- A modified mesothelium
- Does not make germ cells
- Under it: tunica albuginea
Remember 'Germinal' epithelium makes no germ cells.
Exam trap The ovary is not covered by true peritoneum like the uterus; its surface cells are cuboidal, not flat.
Why the other options are wrong
- Source of new oogonia in adults No oogonia are formed after fetal life.
- Stratified germ cell layer It is a single cuboidal layer.
- Granulosa cell precursors Granulosa cells come from the sex cords.
- Endodermal yolk sac lining Germ cells only pass through the yolk sac wall; this layer is mesothelial.
Where this sits in the CPSP syllabus
- Obstetrics & Gynaecology, Paper 2: Histology, Ovary and fallopian tube histology; follicles and corpus luteum