HISTO ● HISTOLOGY SHIFT

M16: FEMALE REPRODUCTIVE SYSTEM

#4
CATHERINE JOIE CARELLE ROUX-ONG, MD, MHPEd, FPOGS, FPSMFM, FPSUOG APRIL 5, 2022

LECTURE OUTLINE B. FEMALE REPRODUCTIVE SYSTEM IN A NON-PREGNANT STATE

I Female Reproductive System ● In a non-pregnant state, the female reproductive system undergoes
A. Major Functions of the Female Reproductive System continuous cyclic changes from puberty to menopause
B. Female Reproductive System in a Non-Pregnant State ● When ovulation is not followed by implantation of the fertilized ovum, the
thick mucosal lining – the endometrium, degenerates and shed in a period
II Ovary of bleeding – menstruation
A. Primordial Germ Cell Development ● First day of menstruation / menses marks the beginning of a new cycle – the
1. Primordial Follicle menstrual cycle
2. Primary Follicle ● 28 days – length of a standard menstrual cycle
3. Secondary Follicle ○ May vary from 21-35 days
4. Graafian Follicle ● Ovulation – occurs at midpoint of the cycle
III Uterus
A. Characteristics
B. Menstrual/ Uterine Cycle
1. Changes in endometrium `
C. Endometrial Changes after Menopause
D. Myometrium Pathologies
IV Cervix
A. Pap Smear
V Placenta
A. Decidua
B. First Trimester
C. Third Trimester
VI Vaginal Birth Canal
A. Mucosal Layer of the Vaginal Wall
VII Fallopian Tube
A. General Characteristics
B. During Ovulation
C. Cross Section of Fallopian Tube
D. Epithelium of Fallopian Tube
E. Ectopic Pregnancy
VIII Mammary Gland
A. General Characteristics
B. Types of Mammary Glands
C. Resting Mammary Glands
D. Lactating Mammary Glands
IX References
X Review Questions Figure 1. Ovarian Cycle
XI Appendix Wikipedia

I. FEMALE REPRODUCTIVE SYSTEM

● 3 Structural Units: (on the basis of their functions)
○ Ovaries
○ Genital tract:
■ Fallopian tubes / Oviduct (paired) – site of fertilization of the ova by the
spermatozoa
■ Uterus – muscular organ that is the site of implantation of fertilized
ovum
■ Cervix – opens to expel fetus into the vagina
■ Vagina – reception of the penis during coitus; passage of the fetus to
the external environment at birth
■ Vulva
○ Breasts – provide nourishment to the newborn

A. 6 MAJOR FUNCTIONS OF THE FEMALE REPRODUCTIVE SYSTEM

1. Production of female gametes – ovaries Figure 2. Ovarian Cycle
2. Reception of male gametes – vagina iStock
3. Provisions for suitable environment for fertilization – fallopian tubes
4. Provision of an environment for the development of the fetus – uterus II. OVARY
5. A means for expulsion of the fetus – cervix ● Paired structure on either side of the uterus
6. Nutrition of the newborn – mammary glands ● Site of oogenesis
● Endocrine organ: produces estrogen and progesterone

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● Ovulation and ovarian hormone production are controlled by the cyclic
release of gonadotrophic hormones (LH and FSH) from the anterior pituitary
gland
● Estrogen and progesterone regulate LH and FSH by a feedback mechanism
● Diameter: 3-5 cm
● Shape: Ovoid
● Fine collagen fibers and ground substance constitute the stroma
● Presence of cortex and medulla
● Cortex
○ Contains numerous follicles that contain gametes in various stages of
development
○ Tunica albuginea – superficial cortex
■ More fibrous than the deep cortex
■ However, unlike the testis, this is NOT an anatomically distinct capsule
(Wheater)
● Germinal epithelium
○ On the surface of the ovary
○ Misleading name
○ Continuation of the peritoneum
● Medulla
○ Central zone
○ Highly vascular – thick-walled blood vessels
○ Contains hilus cells – morphologically very similar to Leydig cells of the
testis Figure 5. Cross section through a normal ovary showing developing follicles
and ovum release
TasmeemME.com

Figure 6. Ovarian cycle

Recorded lecture

A. PRIMORDIAL GERM CELL DEVELOPMENT

Figure 3. Cortex and medulla of an ovary

Slideshare.net

Figure 7. Ovarian cycle

Quizlet

Figure 4. Ovarian cortex
Principles of Anatomy and Physiology, 11/e
Yellow arrow: Note the single layer of low (?) cuboidal mesothelial cells
● Presence of corpus luteum and corpus albicans after puberty
○ Corpus luteum – responsible for estrogen and progesterone production
■ Primarily produces progesterone
○ Corpora albicantes / corpus albicans – degenerate and former corpus
luteum
○ Further degeneration leads to an atretic follicle
● Text in Figure 7:
○ Germinal epithelium – undergoes mitosis to make cells that undergo
meiosis
○ Primordial follicles – dormant cells partway through meiosis
○ Primary follicles – a few each month are stimulated to resume meiosis
○ Mature follicle – contains primary oocyte
○ Secondary oocyte – will be released by the mature follicle at ovulation
○ Ovulated egg – normally, just one egg is released each month
○ Corpus luteum – survives if egg is fertilized and produces progesterone
● During early fetal development, primordial germ cells – oogonia – migrate
to the ovarian cortex, where they multiply by mitosis
● By the 4th or 5th month of fetal development, several million primordial
follicles – primary oocytes
○ Some oogonia enlarge and assume the potential for development into
mature gametes (Doc points at primordial follicle in Figure 7)
○ At this stage they are called primary oocytes and commence the first
stage of meiotic division (Wheater)

(TWG) REQUIERME, REQUIZO, REYES, A., REYES, D., REYES, J.; (TEG) REYES, W., RICAFUENTE, RIGOR, ROJO, ROLLOM 2
 1. PRIMORDIAL FOLLICLE ● During each ovarian cycle, a cohort of up to 20 primordial follicles are
activated to begin the maturation process. (Doc points at primary follicles in
Figure 7)
● Usually, only one follicles reaches full maturity and undergoes ovulation
while the remainder regress before this point (Doc points at mature follicle in
Figure 7)
○ Reason for this apparent wastage is unclear
○ During maturation, however, the follicles have an endocrine function
which may be far beyond the capacity of a single follicle and so the
primary purpose of the the other follicle may to be act as an endocrine
gland (Wheater)
● Follicular maturation involves changes in the oocyte, in the follicular cells,
and in the surrounding stromal tissue (Wheater)
● Follicular maturation is stimulated by FSH secreted by anterior pituitary
gland.
● Figure 10: Oocyte is greatly enlarged
● Granulosa cells – follicular cells that have multiplied and become cuboidal
Figure 8. Primordial follicle in shape
Medcell.med.yale.edu ● Zona glomerulosa – several cell thick layer formed as the granulosa cell
begin to proliferate
● 7th month: A single layer of flattened follicular cell surround the primary ● Zona pellucida – thick homogeneous layer of glycoprotein and acid
oocyte to form the primordial follicle proteoglycans developing between the oocyte and follicular cells
○ This encapsulation arrests the 1st meiotic division and no further
development of primordial follicles occurs until after the female reaches
sexual maturity (puberty)
○ The process of meiotic division is only completed during follicular
maturation, leading up to ovulation and fertilization
○ Thus, ALL the female germ cells are present at birth, but the princess of
meiotic division is only completed some 15 to 50 years later
○ In contrast, in males, meiosis division of germ cells commences only after
sexual maturity and formation and maturation of spermatozoa are
accomplished within about 70 days (Wheater)
○ Female germ cells may undergo degeneration (atresia) at any stage of
follicular maturation
● Figure 8:
○ Primordial follicles/ undeveloped follicles are composed of a primary
oocyte surrounded by a single layer of follicular cells
○ Has a large nucleus and a very prominent nucleolus
○ Once stimulated, it increases in size to become the primary follicle
● At birth: 500, 000 follicles
● Puberty: 300, 000 follicles
Figure 11. Primordial follicle
2. PRIMARY FOLLICLE Recorded lecture

● Theca folliculi – organized layer around the follicle

○ Separated from the granulosa cells by a basement membrane
○ Formed by surrounding stromal cells (Wheater)

3. SECONDARY FOLLICLE
● Primary follicle develops to form the secondary follicle
● Situated deep in the ovarian cortex
● Zona glomerulosa
○ Continues to proliferate
○ Follicular antrum: small fluid-filled space within zona glomerulosa

Figure 9. Early primary follicle

medcell.med.yale.edu
This micrograph was NOT SHOWN in the lecture but was included as a
supplementary figure

Figure 12. Follicular antrum

Recorded lecture

● Once the oocyte has reached its full size, it becomes situated eccentrically
in the thickened area of the granulosa (cumulus oopherus)
Figure 10. Late primary follicle ● At the periphery, theca folliculi develops into 2 layers:
medcell.med.yale.edu ○ Theca interna
In the PPT, the late and early primary follicles were not distinguished from ■ Several layers of rounded cells
each. This figure was simply labeled “primary follicle”
(TWG) REQUIERME, REQUIZO, REYES, A., REYES, D., REYES, J.; (TEG) REYES, W., RICAFUENTE, RIGOR, ROJO, ROLLOM 3
 ■ Have typical steroid-secreting cells that produce estrogen precursor ● After ovulation, ruptured follicle collapses and fills with blood clots to form
(i.e. androstenedione) corpus luteum of menstruation
○ Theca externa ● Under the influence of LH (secreted by anterior pituitary gland), granulosa
■ Less well-defined cells increase greatly in size and begin to secrete progesterone
■ Spindle-shaped cells ● Granulosa cells acquire characteristics of steroid-secreting cells and are
■ NO endocrine function now called granulosa lutein cells
● At this stage, the oocyte becomes as secondary oocyte → commences the ● Progesterone promotes changes in endometrium that make it ready for
second meiotic division implantation if fertilization occur
● Cells of theca interna increase in size and become known as theca lutein
cells
○ Secrete estrogen (like granulosa cells) to maintain thickened uterine
mucosa

Figure 13. Secondary follicle

Recorded lecture
Figure 15. Graafian follicle after ovulation.
Recorded lecture
Primary Follicle Secondary Follicle
● Granulosa cells appear as large, polygonal cells with abundant pale,
● Made up of several layers of ● Contain antral fluid eosinophilic cytoplasm and round nuclei
cuboidal cells ○ Secrete mainly progesterone
● Theca externa: darkly-stained
● Theca interna: pale cytoplasm due to the lipid content; secrete estrogen
4. GRAAFIAN FOLLICLE precursor

● Further growth of the oocyte ceases

IMPORTANT: Dr. Alita Santos mentioned that hyperplasia of the uterus
● First meiotic division is completed just before ovulation
occurs when there is an abundance of estrogen produced.
● Follicular antrum enlarges markedly
● Zona glomerulosa forms layer of even thickness around the periphery of the
follicle
● Cumulus oophorus diminishes → leave oocyte surrounded by corona
radiata (layer of several cells thick)
● Remain attach to zona glomerulosa by thin bridges of cells
○ Before ovulation, bridges break down and oocytes surrounded by corona
radiata floats freely within the follicle
● Follicle has reached the size of around 1.5 to 2.5 cm
● At ovulation, mature follicle ruptures
○ Ovum is expelled into peritoneal cavity near the entrance of fallopian tube
■ Made up of oocyte, zona pellucida, corona radiata

Figure 16. Corpus luteum

Recorded lecture

● Corpus albicans / Corpora albicantes

○ With inactive fibrous tissue mass that forms following involution of corpus
luteum

Figure 14. Graafian Follicle

Recorded lecture

(TWG) REQUIERME, REQUIZO, REYES, A., REYES, D., REYES, J.; (TEG) REYES, W., RICAFUENTE, RIGOR, ROJO, ROLLOM 4
 IMPORTANT: Dr. Roux-Ong emphasized that the stratum basalis layer is
not shed during menstruation while the stratum functionalis sheds during
menstruation

Figure 17. Corpus albicans

Recorded lecture

III. UTERUS
● Muscular organ
● Uterine lining undergoes cyclic proliferation under the influence of ovarian
hormones Figure 20. Endometrium and Myometrium of the Uterus. Stratum
● Site of implantation of the fertilized ovum and subsequent development of functionalis consists of the stratum compactum (top yellow arrow) and the
the placenta stratum spongiosum (middle yellow arrow). The stratum basalis (bottom yellow
artery) is the basal layer adjacent to the myometrium. Branches of the uterine
artery (red arrow) pass through the myometrium and divide into straight and
spiral arteries.
Source: Recorded lecture

● Uterine Artery - branches pass through the myometrium. ○

○ Spiral Arteries - responsive to hormonal changes of the menstrual cycle.
○ Withdrawal of progesterone secretion at the end of the cycle causes
these spiral arteries to constrict.
■ Precipitates ischemic changes that precedes menstruation.
● Histological features respond to hormonal influence:
○ Proliferative change with estrogen effect
○ Secretory change with progesterone effect

B. MENSTRUAL CYCLE
● Typically, the menstrual cycle is around 20 days in length
○ The length may vary among women
Figure 18. Uterus. Top arrow is the myometrium. Right arrow shows the ● Menstrual Phase (Day 1): Endometrial shedding occurs if there is no
endometrium. fertilization or implantation
Source: Recorded lecture ○ Menstruation lasts for around 5 days
● Proliferative Phase (Day 5-14): Endometrial stroma proliferates
A. CHARACTERISTICS OF THE UTERUS ○ Endometrial stroma becomes thicker, richly vascularized
○ Simple tubular glands elongate to form numerous long coiled glands
● Presence of 3 coats: ● Ovulation (Day 14)
○ Endometrium - provides the environment for fetal development. ○ Last part of the proliferative phase
○ Myometrium - thick, smooth muscle wall which expands during ○ Marks the start of the secretory phase
pregnancy. ● Secretory Phase (Day 15-28): second half of the cycle
■ Provides protection for the fetus in a mechanism for expulsion of the ○ Release of progesterone from the corpus luteum after ovulation will
fetus during parturition and delivery. promote production of copious thick glycogen-rich secretion by
○ Perimetrium endometrial glands
○ Ends at the onset of the next menstrual cycle

1. CHANGES IN THE ENDOMETRIUM

● Early Proliferative Phase
○ Thin endometrium
■ Consists of stratum basalis, stratum spongiosum, and stratum
compactum
○ At this phase, glands are sparse and straight
■ As the glands, stroma, and vessels proliferate, the endometrium
becomes thicker
Figure 19. Epithelial lining of the uterus ■ By day 5 or 6, the epithelium has already started regenerating
Simple low columnar cells with ciliated areas ○ Proliferating glandular epithelium can be seen at higher magnification
Source: Recorded lecture ■ Consists of columnar cells, basally located nuclei, and prominent
nucleoli
● Lining epithelium - simple low columnar cells with cilia.
● Tunica Propria of embryonic connective tissue
● Presence of highly branched tubular glands, uterine glands.
● Endometrium is divided into:
○ Stratum basalis
■ deepest, basal layer
■ Adjacent to the myometrium
■ Not shed during menstruation
○ Stratum functionalis
■ functional layer and exhibits dramatic changes throughout the cycle.
■ Sheds during menstruation
■ Stratum spongiosum: intermediate, spongy layer.
■ Stratum compactum: thin layer of superficial cells with a compact
stromal appearance
(TWG) REQUIERME, REQUIZO, REYES, A., REYES, D., REYES, J.; (TEG) REYES, W., RICAFUENTE, RIGOR, ROJO, ROLLOM 5
Figure 21. Early Proliferative Endometrium. Upper left quadrant shows the
different layers of the endometrium on low magnification (C - Stratum
Compactum, S - Stratum Spongiosum, B - Stratum Basalis). Upper right and
lower left quadrants show the straight tubular glands at high magnification Figure 24. Early secretory endometrium (day 16) at high magnification.
(yellow arrows). Lower right quadrant shows the proliferating glandular Note that the glycogen accumulates and forms vacuoles at the basal aspect of
epithelium at higher magnification (yellow arrow). the cell (yellow arrow). This is what you call basal vacuolization and it appears
Source: Recorded lecture on day 16 of the cycle. This is the characteristic feature of the early secretory
endometrium.
● Late Proliferative Phase Source: Recorded lecture
○ Endometrium has doubled in thickness
○ Stroma is edematous
○ Tubular glands are now becoming more coiled and closely packed
○ Little change in stratum basalis
○ Since there is continuous change, precise dating of the menstrual cycle is
inaccurate during the proliferative phase

Figure 25. Late Secretory Endometrium. This phase is characterized by a

“saw tooth” appearance of the glands (upper left yellow arrow) containing
copious glycogen and protein-rich secretions. The stroma is now at its most
vascular. Fluid begins to accumulate in between the stromal cells (i.e., stroma
is edematous) (lower right yellow arrow).
Source: Recorded lecture
Figure 22. Late Proliferative Endometrium. Tubular glands are now more
coiled and closely packed (yellow arrow) ● Endometrial stromal granulocytes and large granular lymphocytes are often
Source: Recorded lecture found in the stroma of the secretory stage
○ Changes in the secretory endometrium make more precise dating
● Secretory Phase possible on histological specimens as compared to the proliferative phase
○ Start of the phase is marked by ovulation ● Premenstrual Phase
○ On low magnification, the coiled appearance of the glands is more ○ In the absence of implantation of the fertilized ovum, degeneration of the
pronounced corpus luteum results in cessation of estrogen and progesterone
○ Endometrium reaches its maximum thickness under the influence of secretion
progesterone ■ This initiates spasmodic constriction of the spiral arterioles of the
○ Glandular epithelium is stimulated to synthesize glycogen endometrium in the stratum functionalis
○ This results in ischemia, which is manifested by the degradation of the
superficial layer of the endometrium and leakage of blood into the stroma

Figure 23. Secretory endometrium Figure 26. Premenstrual endometrium

Coiled appearance of the glands are seen at low magnification. Picture on the right shows degradation of the superficial layer of the
Source: Recorded lecture endometrium due to ischemia.
Source: Recorded lecture
(TWG) REQUIERME, REQUIZO, REYES, A., REYES, D., REYES, J.; (TEG) REYES, W., RICAFUENTE, RIGOR, ROJO, ROLLOM 6
 D. MYOMETRIUM PATHOLOGIES
● Myometrium
○ Composed of smooth muscle bundles and is seen below the endometrial
layer

Figure 27. Menstrual endometrium. Further ischemia leads to degradation of

the whole functional layer which is progressively shed off as menstruation.
Note that there is blood within the stroma.
Source: Recorded lecture

Summary of the cyclic changes which occurs in the endometrium

● Proliferative Phase Figure 30. Myometrium.
○ Short endometrial glands Source: Recorded lecture
● Secretory Phase ● Uterine Fibroids
○ Occurs after ovulation ○ This is also known as uterine leiomyomas
○ Early Secretory Phase: characterized by subnuclear vacuolization ○ Benign tumors on the myometrium
■ Vacuolizations are filled with glycogen
■ Starts 36 hours after ovulation, alongside corpus luteum
○ Late Secretory Phase: endometrium reaches maximum thickness
● Menstrual Phase
○ If pregnancy does not ensue, the endometrium is shed off as
menstruation.

Figure 31. Uterine fibroids.

Source: Recorded lecture

Figure 28. Summary of Cyclic Changes

Source: Recorded lecture

C. ENDOMETRIAL CHANGES AFTER MENOPAUSE

● After menopause, cyclic production of estrogen and progesterone from the
ovaries ceases
○ Entire genital tract undergoes atrophy
● The endometrium is now thin and consists only of stratum basalis
● Glands are sparse and inactive

Figure 32. Laparoscopic view of the uterus with multiple myomas. Yellow
arrow - uterus. Green arrows - myomas.
Source: Recorded lecture

IV. CERVIX
● Opens to expel the fetus into the vagina
● Cervix protrudes into the vagina
● Functions:
○ Admits spermatozoa to the genital tract
Figure 29. Atrophic endometrium. Upper left shows an atrophic ○ During pregnancy - it protects the uterus and the upper tract from
endometrium consisting only of stratum basalis (arrow). Upper right shows bacterial invasion
inactive glands (arrow). In some women, the glands become dilated, as seen ○ During parturition - it dilates to allow the passage of the fetus
in the lower left (arrow), and form cystic spaces. At higher magnification, these
glandular epithelial cells are cuboidal or low columnar with no mitotic figures.
Source: Recorded lecture
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Figure 33. Cervix viewed during a speculum examination. Note the Ectocervix Figure 36. Squamo-columnar Junction (yellow arrow), the transition point of
and Endocervix. the endocervix and the ectocervix. The stratified epithelium transitions into
Source: Recorded lecture columnar epithelium. The underlying layers of the cervix (blue arrow) are
composed primarily of collagenous and elastic connective tissue rather than
● Cervix shows 2 types of epithelium: smooth muscle fibers.
○ Thick interlacing muscular coat of smooth muscle arranged in 3 ill-defined Source: Recorded lecture
layers.
○ Simple columnar (endocervix)
A. PAPANICOLAOU METHOD (PAP SMEAR)
■ Endocervical canal is lined by a single layer of tall columnar mucous
secreting epithelial cells where the cervix is exposed to a more hostile ● The transformation zone may be studied by scraping cells from the surface
environment of the vagina. using a spatula or brush and smearing it on a slide
● Screening tool for cervical malignancy

Figure 34. Endocervix

Source: Recorded lecture
Figure 37. Papanicolaou Method
○ Stratified squamous non-keratinizing (ectocervix) Recorded Lecture
■ Ectocervical canal is lined by a thick stratified squamous epithelium as
seen in the vulva and vagina.
■ Cells of the ectocervix have clear cytoplasm due to the high content of
glycogen.

Figure 35. Ectocervix

Recorded lecture

○ Squamo-columnar Junction
■ Also known as Transitional Zone
■ It is a transition point between these two epithelia. Figure 38. Cells that can be seen when pap smear is performed.
■ The junction between the ectocervix and the endocervix is quite abrupt. Source: Recorded Lecture

IMPORTANT: The squamo-columnar junction or the transformation zone is ● Superficial cells or surface cells - contains small contracted nuclei and
that it may undergo malignant change causing cancer of the cervix. This is pink cytoplasm
considered as the center of attention during the Pap smear. ● Intermediate cells - contains plump nuclei and cytoplasm stains blue

(TWG) REQUIERME, REQUIZO, REYES, A., REYES, D., REYES, J.; (TEG) REYES, W., RICAFUENTE, RIGOR, ROJO, ROLLOM 8
 Figure 39. Human Papillomavirus
Source: Recorded Lecture

IMPORTANT: Cervical cancer is caused mainly by HPV 16 and HPV 18. Pap
Smear is a screening modality for early signs of cervical cancer.

V. PLACENTA
Figure 42. Decidua Cells under higher magnification (yellow arrow) as they
● Performs a remarkable range of functions until fetal organs become present as large polygonal cells that store glycogen and lipids.
functional such as: Source: Recorded Lecture
○ Gas exchange
○ Excretion ● During the process of implantation, secretion of hCG (human chorionic
○ Maintenance of homeostasis gonadotropin) from the syncytiotrophoblast interrupts the ovarian cycle.
○ Metabolic functions ○ This results in the growth and proliferation of stromal cells of the
○ Hemopoiesis endometrial stratum functionalis at the implantation site into large
○ Hormonal secretions polyhedral decidual cells (yellow arrow), a change that has already begun
● Placenta is very important in utero as the fetus is dependent on the placenta in the late secretory phase.
● Ultimately, expansion of the embryo and its enveloping fluid-filled membrane
system results in fusion of the capsular and parietal layers of the decidua,
with complete obliteration of the uterine cavity.

Figure 40. Placenta

Source: Recorded Lecture

A. DECIDUA
● Endometrium of pregnancy

Figure 43. Chorionic Villi. Schematic diagram of a chorionic villi (Left)

Clusters of intermediate trophoblast cells (Right). These can be found in the
fallopian tubes and ovary (pathologic), and placenta (physiologic).
Source: Recorded Lecture

Figure 41. Decidua
Source: Recorded Lecture
● Decidua basalis - the decidua beneath the developing embryo
○ Decidua basalis together with the trophoblast will form the future
placenta
● Decidua capsularis - the decidua that overlies the embryo
● Decidua parietalis - the decidua lining the rest of the uterus
● In the first trimester, chorionic villi of the placenta are large and covered by
two layers of cells.
○ Outer syncytiotrophoblast (yellow arrow) with abundanact pink cytoplasm
and the Inner cytotrophoblast (red arrow).
● Placenta invades into the endometrium to establish a maternal fetal
circulation that would be supporting the growing fetus.
● The underlying decidual plate forms the limit of the placental invasion
IMPORTANT: Syncytial knots and numerous blood vessels dictate
maturity. The knots start to form by the second trimester but not uniformly.

B. FIRST TRIMESTER PLACENTA

● Main feature of the first trimester placenta are the large number of villi (V)
projecting into the lacuna (L), in vivo would be filled with maternal blood
○ Some villi show evidence of branching.

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 ■ Solid cores of cytotrophoblast and intermediate trophoblast can be
seen extending away from the villi to form new branches
○ With further magnification, the villi seem to have a core of primitive
mesenchyme
○ The villi are invested by trophoblast, comprising inner cytotrophoblast
cells and outer syncytiotrophoblast cells.

Figure 46. Stratified squamous non-keratinizing epithelium

Source: Recorded Lecture

A. MUCOSAL LAYER OF THE VAGINAL WALL

Figure 44. First Trimester Placenta

Source: Recorded Lecture

C. THIRD TRIMESTER PLACENTA

● The branching nature of the villi is a feature of the term placenta
■ Compared with early placenta, the villous pattern is much more highly
developed and the average villous diameter is much smaller, reflecting
the extensive branching growth of the villi as the placenta enlarges.
● Characteristics of third trimester placenta are syncytial knots
● Syncytial knots
○ Formed when syncytiotrophoblast nuclei aggregate together in clusters Figure 47. Mucosal layer of the Vaginal Wall
leaving zones of thin cytoplasm devoid of nuclei in between Source: Recorded Lecture

● Walls of the vagina consist of 4 mucosal layers

○ Stratified squamous non-keratinizing epithelium
○ Lamina propria contains many elastin fibers and has a rich plexus of
small veins and is devoid of glands.
○ Smooth muscle bundles are arranged in ill-defined inner circular and
outer longitudinal layers.
○ Outer adventitial layer merges with the adventitial layers of the bladder
anteriorly and the rectum posteriorly.
● The combination of a muscular layer and a highly elastic lamina propria
and outer adventitia permits the gross distension that occurs during
parturition.
● After coitus, involuntary contraction of the smooth muscle layer ensures
that a pool of semen remains in the cervical region.

VII. FALLOPIAN TUBE

Figure 45. Third Trimester Placenta. At low magnification, huge numerous
villi are seen (Left). Syncytial knots (yellow arrows) (Right) ● Also known as “oviduct”
● Site of fertilization
Source: Recorded Lecture ● Conveys the zygote to the uterine cavity
● Segments:
[WHEATER’S] ABNORMALITIES OF THE PLACENTA (page 374) ○ Interstitium
○ Isthmus
The normal placenta invades into the uterine wall in order to establish ○ Ampulla
circulation with a supply of oxygen and nutrients for the developing fetus. In ○ Infundibulum
some cases, the placenta becomes abnormally adherent and invades too ○ Fimbriae/fimbriated end
deeply into the uterus, preventing the normal process of separation which
occurs after parturition. This can lead to serious maternal blood loss. The
least severe form of this is known as placenta accreta, where the placenta
does not invade significantly into the myometrium. Placenta increta describes
deeper attachment which extends further into the myometrium. In its most
severe form, placenta percreta, the placenta may penetrate through to the
serosal surface of the uterus and can even attach to other pelvic organs.

VI. VAGINAL BIRTH CANAL

● Organ for copulation
● Presence of 3 coats - mucosa, muscular, fibrous
● Lining epithelium - stratified squamous non-keratinizing epithelium rich
in glycogen granules
● Tunica propria is areolar connective tissue with abundant blood sinuses Figure 48. Segments of the Fallopian Tube
● Absence of glands Source: North Carolina Center for Reproductive Medicine
(TWG) REQUIERME, REQUIZO, REYES, A., REYES, D., REYES, J.; (TEG) REYES, W., RICAFUENTE, RIGOR, ROJO, ROLLOM 10
 A. GENERAL CHARACTERISTICS D. EPITHELIUM OF FALLOPIAN TUBE
● 3 coats
○ Mucosa
○ Muscular
○ Fibroserous
● Lining epithelium: simple columnar with areas of peg cells and some
areas of ciliated cells
○ Columnar cells of the epithelium are of three types: (Wheater’s p. 360)
■ Non-ciliated secretory cells probably has a role in the nutrition and
protection of the ovum
■ Intercalated cells may be a morphological variant of the secretory
cells
■ Ciliated cells are generally shorter than the secretory cells, making
the epithelial surface somewhat irregular in outline.
■ Scattered intraepithelial lymphocytes are also present
● Presence of complicated mucosal folds especially in the ampulla
● Has a very thin muscular layer
● Fibroserous outer coat with abundant blood vessels

B. DURING OVULATION Figure 51. Note the ciliated columnar cells as well as the peg cells with
● The infundibulum moves to overlie the site of rupture of the Graafian follicle bulbous apical projections lining the branching finger-like projections.
● Finger-like projections called fimbriae direct the ovum into the tube Source: Recorded Lecture
● Movement of the ovum along the tube is mediated by gentle peristaltic
action of the longitudinal and circular smooth muscle layers of the
oviduct wall

Figure 49. Movement of ovum during ovulation

Source: Recorded Lecture Figure 52: Ciliated columnar cells and peg cells.
Source: Recorded Lecture
C. CROSS SECTION OF THE FALLOPIAN TUBE
● Mucosal layer
○ Mucosal lining of the fallopian tube is thrown into a labyrinth of branching
longitudinal folds
■ This feature is most prominent in the ampullary area which is the
usual site of fertilization
● Muscular layer/muscularis
○ 2 layers: inner circular, outer longitudinal (ICOL)
● Serosa
○ Vascular supporting tissue can be found here

Figure 53. On closer/HME view, the columnar cells of the epithelium are made
up of ciliated secretory cells making the epithelium look somewhat irregular in
outline (red arrow). Non-ciliated secretory cells, called peg cells (yellow arrow)
produce secretions that propel towards the uterus.
Source: Recorded Lecture

Figure 50. Cross section of fallopian tube, specifically the ampulla
Source: Recorded Lecture
IMPORTANT: Isthmus has little mucosa lining it. Ampulla region is the most
common site of tubal pregnancy.
E. ECTOPIC PREGNANCY
● Happens when the fertilization of the ovum does not implant into the uterus
but instead, persists in the fallopian tube where fertilization occurs
● Tubal pregnancy
○ Fertilization/pregnancy enlarges in the fallopian tube
● Addressed medically or surgically

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 Figure 53. Ectopic pregnancy occurs when an embryo attaches outside the
uterus in the site of the fallopian tube.
Source: Recorded Lecture

VIII. MAMMARY GLAND

A. GENERAL CHARACTERISTICS
● Highly modified apocrine sweat glands
● The breasts of both sexes follow a similar course of development until
puberty
○ After which, the female breasts develop under the influence of pituitary,
ovarian and other hormones
○ Until menopause, the breasts undergo cyclical changes in activity which
are contolled by the hormones of the ovarian cycle
○ After menopause, the breasts, like the other female reproductive tissues
undergo progressive atrophy and involutional change
● Each breast consists of 15-25 independent units called “breast lobes” and
each lobe consists of a compound tubular acinar gland
○ The lobes are embedded in a mass of adipose tissue subdivided by
collagenous septa
● The duct forms a dilatation called, lactiferous acinus before opening into
the surface
● The nipple contains smooth muscles and contraction of the muscles causes
erection of the nipple
Figure 55. Differentiation between the 2 types of mammary glands. Note on
the right (lactating mammary gland) is filled with milk, and on the upper part
are myoepithelial cells.
Source: Recorded Lecture
C. RESTING MAMMARY GLANDS
● Has inactive glandular tissue and lots of dense connective tissue
● Each lobe comprises of compound tubular acinar cells, and the acini
empties into the ducts
● The breast ducts and acini are lined by 2 layers of cells:
○ Inner luminal layer of epithelial cells
○ Basal layer of the myoepithelial cells
● Bigger ducts: Luminal cells are tall columnar
● Smaller ducts: Luminal cells are small cuboidal

Figure 54. Shows the sagittal section of the breast wtih the different parts.
Source: Recorded Lecture

[WHEATER’S] PAGET’S DISEASE OF BREAST (page 378)

Invasive breast cancer or carcinoma in situ may spread through ducts and
along the lactiferous sinus from the underlying breast lobe and may even
spread into the surface epidermis, where it is known as Paget’s disease of
the breast. Clinically, this disease typically presents as a patch of red, scaly,
seemingly inflamed skin around the nipple, closely mimicking eczema, a
common inflammatory skin disease. In this setting, it is important to examine
carefully for any underlying breast lump. Skin biopsy may be performed to
allow definitive diagnosis.

B. TYPES OF MAMMARY GLANDS

● Resting Mammary Gland
○ Rudimentary secretory acini with abundant fibrous stroma and adipose
tissue
● Lactating/Active Mammary Gland
○ Dilated secretory acinar filled with colostrum, a well developed ductal
Figure 56. Micrographs of resting mammary gland.
system and a thin stroma
Source: Recorded Lecture
■ Colostrum is the milk contained in the mammary glands

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 D. LACTATING MAMMARY GLANDS the pathologist determines whether the lesion is indeed a cancer or one of
● Composed mainly of acini filled with colostrum many benign breast lesions that may cause a lump or a mammographic
● Interlobular tissue is reduced into thin septa between the lobules abnormality.
● Milk production proceeds as long as there is sucking
○ Sucking by the newborn is very important as it initiates a neurohormonal E. SUMMARY OF THE FEMALE REPRODUCTIVE SYSTEM
reflex
■ Oxytocin is released from the posterior pituitary lobe which causes ● 3 structural units:
contraction of the myoepithelial cells which embrace the secretory ○ Ovaries
acini and the ducts, propelling milk into the lactiferous sinuses, called ■ Produce female gametes
“milk let-down” ○ Genital tract
● Colostrum ■ Fallopian tubes: provide suitable environment for fertilization
○ Has numerous fats and glycogen ■ Uterus: provides environment for development of the fetus
○ Breast secretion or breast milk available during the first few days of birth ■ Cervix: for expulsion of the fetus
○ Patients are usually advised to breastfeed because colostrum contains ■ Vagina: reception of male gametes
numerous antibodies ■ Vulva
○ Breast/Mammary glands
■ Provide nutrition to the newborn

IX. APA REFERENCES

Roux-Ong, C.J.C. (2021). Female Reproductive System [Pre-recorded file]
Young, B., O’Dowd, G., & Woodford, P. (2014). Wheater's Functional
Histology: A Text and Colour Atlas (6th ed.). Philadelphia, PA:
Elsevier, Inc.

X. REVIEW QUESTIONS

No.
Figure 57. Interlobular connective tissue reduced into thin septa (yellow
arrow). Milk let-down from the contraction of myoepithelial cells (red arrow)
Source: Recorded Lecture
QUESTION
1 Female germ cells may undergo degeneration at any stage of
follicular maturation
2 Under the influence of what hormone does the granulosa cells
increase greatly in size and begin to secrete progesterone
3 What is the epithelial lining of the ectocervical canal?
4 This is formed when syncytiotrophoblast nuclei aggregate
together in clusters leaving zones of thin cytoplasm devoid of
nuclei in between.
5 What do you call the non-ciliated secretory cells that produce
secretions that give nutrition and for the protection of the ovum?

No. RATIONALIZATION
1 True
2 Luteinizing hormone
3 Stratified squamous non-keratinizing
4 Syncytial knots
5 Peg cells

XII. APPENDIX

Figure 58. Breast with numerous dilated acini filled with “colostrum” and
dilated lactiferous ducts
Source: Recorded Lecture

[WHEATER’S] OTHER EFFECTS OF LACTATION (page 381)

The hormonal changes which occur during lactation may interrupt resumption
of the normal menstrual cycle following pregnancy and childbirth. As a result,
a substantial proportion of women have lactational amenorrhoea whilst breast
feeding. High levels of prolactin act to suppress production of LH and so
effectively inhibit ovulation. This is an important means of birth control in
some cultures.

[WHEATER’S] BREAST CARCINOMA (page 382)

Carcinoma of the breast is one of the commonest malignant tumours of
women, leading to many premature deaths and great morbidity. In many
countries, breast cancer screening programmes are in operation in the hope
that early detection of cancer or even precancerous lesions will cure the
disease. Women in the age groups at risk are subjected to mammography, an
uncomfortable and undignified procedure that is nevertheless better than
dying of breast cancer. Lesions identified at mammography are biopsied, and

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