Histology,

Embryology,
Physiology
Tutor 9
Histology
 01.
Male
Testis
● The testis are ovoid
organs responsible
for sperm production
● Tunica Albuginea -
kapsul jaringan ikat
tebal.
● Leydig/Interstitial
Cells - ditemukan di
jaringan ikat (atau
interstitium) antara
tubulus seminiferus.
Interstitial Tissue
● Jaringan interstisial
testis terdiri dari
jaringan ikat tipis yang
mengandung
fibroblasts, lymphatics,
dan pembuluh darah.
● Sekresi testosteron
dipicu oleh
gonadotropin hipofisis
yang juga disebut
interstitial cell-
stimulating hormone
(ICSH).
 Seminiferous Tubules
● Sperma diproduksi di tubulus seminiferus dengan kecepatan sekitar 2 × 108 per
hari pada dewasa muda.
● Setiap testis memiliki 250 hingga 1000 tubulus seperti itu di lobulusnya, dan
setiap tubulus berukuran diameter 150-250 mikrometer dan panjang 30-70
mikrometer.
● Spermatozoa diproduksi di epitel germinal tubulus seminiferus dan dilepaskan
ke lumina duktus.

There are two distinct types of seminiferous

tubules:
1. Convoluted
2. Straight
 Spermatogenesis
● Spermatogenesis adalah proses pembentukan sperma yang terjadi di dalam
tubulus seminiferus
Clonal Nature
of Spermato-
genesis
 Spermiogenesis
Proses dimana spermatid berdiferensiasi menjadi
spermatozoa

● Pembentukan acrosome
● Kondensasi dan elongasi nukleus
● Pembentukan flagellum
● Kehilangan banyak sitoplasma

Hasil: mature spermatozoon → dilepaskan dari

permukaan sel Sertoli ke lumen tubulus
 Sertoli Cells
● Karakteristik:
○ Tall columnar or pyramidal epithelial cells → membentuk basal lamina dari
seminiferous tubules
○ Melekat pada basal lamina, ujung apikalnya meluas ke lumen
○ Mengandung SER yang melimpah, beberapa ER kasar, Golgi complexes,
banyak mitochondria, dan lysosomes
○ Nukleus→ ovoid or triangular, euchromatic, memiliki nukleolus yang menonjol
● Blood-testis barrier → tight occluding junctions diantara basolateral membranes
→ mencegah serangan autoimun terhadap sel spermatogenik
● Fungsi:
○ Support, proteksi, and nutrisi sel spermatogenik yang sedang berkembang
○ Sekresi eksokrin dan endokrin
○ Fagositosis
 Intratesticular Ducts
Membawa spermatozoa dan liquid dari seminiferous
tubules ke duct of the epididymis
 Rete Testis
Dilapisi cuboidal
epithelium dan didukung
oleh jaringan ikat dari
Straight Tubules mediastinum Efferent Ductules
Dilapisi sel Sertoli Dilapisi unusual epithelium
(nonciliated cuboidal cells
& taller ciliated cells) →
memiliki gambaran khas
bergelombang
 Excretory Genital
Ducts
Mengantarkan sperma dari skrotum ke penis
selama ejakulasi
 Epididymis
● Duktus berkelok panjang, dikelilingi jaringan ikat
● Terletak di dalam skrotum sepanjang sisi superior
dan posterior masing-masing testis
● Panjang 4-5 m
● Bagian
○ Head : daerah masuknya efferent ductules
○ Body : tempat sel sperma mengalami modifikasi
halus lebih lanjut
○ Tail : tempat sperma disimpan sampai ejakulasi
● Perjalanan sperma di duktus epididimis: 2-4 minggu.
 Epididymis
● Dilapisi
pseudostratified
Pematangan sperma pada epididimis
columnar epithelium
terdiri dari columnar 1. Perkembangan motilitas
principal cells, dengan untuk bergerak secara
stereocilia panjang & independen
small basal stem cells 2. Maturasi akrosom
● Dikelilingi oleh thin, 3. Perubahan biokimia dengan
circular layer of penambahan kolesterol dan
smooth muscle cells faktor dekapasitas lain.
 Vas Deferens

● Tubulus lurus panjang berdinding otot tebal,

dinding otot dan lumen yang relatif kecil, berlanjut
ke prostatic urethra
● Lamina propria mengandung banyak serat elastis,
dan lapisan epithelial berlapis dengan beberapa
sel memiliki stereosilia jarang
● Muskularis sangat tebal terdiri dari lapisan sirkular
dalam dan lapisan longitudinal luar.
● Selama ejakulasi otot-otot menghasilkan kontraksi
peristaltik kuat, yang secara cepat menggerakkan
sperma di sepanjang duktus ini dari epididimis
 Accessory Glands

Memproduksi sekret yang bercampur dengan

sperma selama ejakulasi untuk menghasilkan semen
 Seminal Vesicles
● Karakteristik: 2 tabung yang sangat berkelok, panjang
sekitar 15 cm, ditutupi kapsul jaringan ikat.
● Terdapat sejumlah besar lipatan tipis dan kompleks
yang dilapisi dengan simple/pseudostratified columnar
epithelial cells yang kaya secretory granules
● Lamina propria mengandung serat elastis & dikelilingi
otot polos yang berfungsi untuk mengosongkan kelenjar
selama ejakulasi.
● Kelenjar eksokrin → mensekresi sebagian besar cairan
semen, termasuk nutrien sperma.
● Komponen cairan: Fruktosa (sumber energi),
Prostaglandin (stimulasi aktivitas di sistem reproduksi
wanita), dan Fibrinogen (untuk koagulasi semen setelah
ejakulasi
 02.
The Female
Reproductive System
01.
Ovaries
P ; 3 cm
L ; 1,5 cm
Th ; 1 cm

Ditutupi ; epitel selapis kuboid (epitel germinativum) → berlanjut

mesotel
Menutupi selapis simpai jaringan ikat padat (tunica albuginea)

Isi ovarium
- Korteks ( regio yang terisi stroma jaringan ikat yang
banyak mengandung sel dan banyak folikel ovarium dengan
ukuran bervariasi pada vagina orang dewasa)
- Medula (bag. Terdalam ovarium) – mengandung jaringan
ikat longgar dan pembuluh darah yang memasuki organ
melalui hilum dari mesenterium yang menahan ovarium
- Tidak ada batas tegas antara daerah korteks dan medulla
ovarium
Early Development of the Ovary
- Bulan 1 = populasi sel benih primordial migrasi ke kantong kuning (yolk sac) ke primordia gonad. Gonad
(Sel-sel membelah dan berdiferensiasi – oogonia) .
- Bulan 5 = saat embrio berusia 2 bulan, terdapat 600.000 oogonia yang menghasilkan > 7 juta sel
- Bulan 3 = oogonia masuk profase dari pembelahan meiosis pertama, terhenti di tahap meiosis berikutnya
karena sudah menyelesaikan sinapsis dan rekombinasi
- Sel yang terhenti = oosit primer
- Sel-sel folikel = tempatnya di folikel ovarium, sel penyangga pipih yang mengelilingi oosit primer
- Menjelang bulan 7 = kebanyakan oogonia telah bertransformasi menjadi oosit primer di dalam folikel
- Atresia = proses degeneratif perlahan di folikel yang melenyapkan oosit primer
- Pubertas = ovarium mengandung 300.000 oosit
- Reproduksi = 30-40 thn , sekitar 450 oosit yg dibebaskan dari ovarium melalui ovulasi
Ovarian Follicles
Follicular Growth & Development

Sel folikel
 Follicular Atresia

Atresia → apoptosis → awal, makrofag

menginvasi folikel yang berdegenerasi dan
memfagositosis debris → membentuk suatu
jaringan parut kolagen → berlangsung di
beberapa kejadian ( EX: sesaat setelah lahir
atau selama pubertas dan kehamilan)
Corpus Luteum

● Corpus luteum = sel-sel granulosa dan theca interna folikel ovarium yang menyusun diri membentuk suatu kelenjar endokrin
● Sel lutein granulosa = ukuran sel granulosa yang bertambah (20-35 um), tanpa membelah dan akhirnya menempati 80% parenkim corpus
luteum
● Sel lutein theca = bekas theca interna yang menjadi peran komponen lain corpus luteum
● Corpus luteum menstruasi = corpus luteum yang bertahan sebagian dari siklus mens
● Corpus albicans = fibroblast yang memasuki daerah corpus dan membentuk parut jaringan ikat padat
● Corpus luteum kehamilan = yang bertahan dari siklus kehamilan
● HCG (human chorionic gonadotropin) = mencegah penurun kadar progesteron , sel-sel trofoblast embrio yang berimplantasi
menghasilkan suatu hormon glikoprotein
Ovulation & Its
Hormonal
Regulation
02.
Uterine Tube
Deretan regio sepanjang tuba uterina

⁕ Infundibulum, bukaan berbentuk corong yang

dibatasi dengan ekstensi seperti jari yang disebut
fimbriae (L., pinggiran) di sebelah ovarium;
⁕ Ampulla, wilayah terpanjang dan diperluas di
mana pembuahan biasanya terjadi;
⁕ isthmus, bagian yang lebih sempit lebih dekat
dengan rahim; dan
⁕ Uterine atau intramural, yang melewati dinding
rahim dan terbuka ke bagian dalam ini organ.
The epithelium contains two interspersed, functionally
important cell types:

● Ciliated cells in which ciliary movements

sweep fluid toward the uterus.
● Secretory peg cells, nonciliated and often
darker staining, often with an apical bulge into
the lumen, which secrete glycoproteins of a
nutritive mucus film that covers the epithelium
03.

Major Events of
Fertilization
 Fertilization
⇒ union of female and male gametes.
Occurs in the ampulla of a uterine tube.

Major steps:
● Capacitation of sperm
● Acrosomal reaction
● Sperm penetration to the corona radiata
● Cortical reaction
● Secondary oocyte nucleus completes meiosis II,
single penetrating sperm nucleus undergoes
decondensation
● Fusion -> zygote

https://www.researchgate.net/figure/Main-events-produced-during-the-fertilization-in-the-different-anatomical-regions-
of-the_fig2_44806575
04.

Uterus
 Uterus
Major regions of the uterus:
● Body
● Fundus
● Isthmus
● Cervix

https://www.ndvsu.org/images/StudyMaterials/Anatomy/histology-of-female-
reproductive-system.pdf

Major layers of the uterine wall:

● Perimetrium ▸ serosa layer covered by
mesothelium
● Myometrium ▸ thick vascularized smooth muscle
● Endometrium ▸ inner mucosal layer lined by simple
columnar epithelium

Junqueira Basic Histology, 12th Ed.

 myometrium

● Thickest layer, shows bindles of smooth

muscle fibers with lots of plexuses and
lymphatics.
● During pregnancy, goes through a period of
extensive growth involving hyperplasia and
hypertrophy, contract forcefully during
parturition.
● After pregnancy, smooth muscles shrink and
may undergo apoptosis, back to it’s
prepregnancy size.
Junqueira Basic Histology, 12th Ed.
 endometrium

→ primarily nonbundled type II collagen fibers.

Has 2 concentric zones:
● Basal layer
○ Underlying portion
○ Regenerates the functional layer
● Functional layer
→ simple columnar epithelium, consists of
ciliated and nonciliated cells
○ Surface portion, shed during menstruation
○ Uterine glands
Junqueira Basic Histology, 12th Ed.
 endometrium - blood supply

● Arcuate artery
○ Branches of the uterine arteries
● Radial arteries
○ Branch of accurate arteries
○ Extend to the endometrium
● Straight arteries
○ Supply basal layer
● Spiral (coiled) arteries
○ Supply functional layer

Junqueira Basic Histology, 12th Ed.

 Menstrual Cycle

Junqueira Basic Histology, 12th Ed.

Junqueira Basic Histology, 12th Ed.
05.
EMBRYONIC
IMPLANTATION,
DECIDUA, & THE
PLACENTA
EMBRYONIC IMPLANTATION,
DECIDUA, & THE PLACENTA

⁕ Blastomer→ Zigot yang mengalami mitosis

⁕ Morula→ Zigot yang telah membelah
⁕ Ketika zigot sampai di uterine cavity →
blastomer akan membentuk central cavity dan
memulai tahan pertumbuhan blastocyst
⁕ Blastomer menjadi lapisan perifer yang disebut
trophoblast di sekitar rongga, beberapa sel
hanya di dalam lapisan ini membentuk
embryoblast.
⁕ Implantasi→ perlekatan blastocyst ke
permukaan epitel endometrium dan penetrasi
proteolitiknya
EMBRYONIC IMPLANTATION,
DECIDUA, & THE PLACENTA

⁕ Trophoblast→ Mendorong terjadinya implantasi

⁕ Embryoblast→ mengatur pembentukan rongga
amnion dan yolk sac
⁕ Trophoblast berdiferensiasi menjadi:
○ Cytotrophoblast→ lapisan sel yang aktif
secara mitosis segera di sekitar amnion dan
kantung kuning telur
○ Syncytiotrophoblast→ massa non-mitosis
dari sitoplasma berinti banyak yang
menginvasi stroma sekitarnya
EMBRYONIC IMPLANTATION,
DECIDUA, & THE PLACENTA

⁕ The endometrial stroma berubah secara

histologis setelah implantasi
⁕ Fibroblas menjadi membesar, poligonal, lebih
aktif dalam sintesis protein, dan sekarang disebut
sel decidua→ endometrium disebut decidua
⁕ Desidua dibagi menjadi 3 area:
○ Decidua basalis→ area antara implan
embrio dan miometrium
○ Decidua capsularis→ area antara embrio
dan uterine lumen (menipis ketika embrio
tumbuh)
○ Decidua parietalis→ Sisi uterus
EMBRYONIC IMPLANTATION,
DECIDUA, & THE PLACENTA

⁕ Placenta→ Tempat pertukaran nutrisi dan limah

janin
⁕ Daerah ini berasal dari:
○ Embryo→ chorion
○ Maternal→decidua basalis
⁕ Chorionic villi of the developing placenta go through
three stages:
○ Primary Villi→ cytotrophoblast berproliferasi
ditutupi oleh syncytiotrophoblast meluas ke
dalam lakuna yang mengandung darah ibu
○ Secondary Villi→ Berkembang saat primary
villi diserang mesenkim ekstraembrionik
○ Tertiary Villi→ Setelah secondary villi
berdiferensiasi membentuk lengkung kapiler
06.

CERVIX
Cervix

⁕ Cervix secara histologis berbeda dengan bagian

rahim lainnya
⁕ Mukosa endoserviks merupakan lapisan epitel
kolumnar sederhana pada lamina propria yang tebal,
bercabang, mensekresikan kelenjar serviks.
⁕ Mukosa cervical canal merupakan lanjutan dari
endometrium
⁕ Endocervical mucosa terdapat branched cervical
mucous glands
⁕ Pada bagian dalam dindingnya berupa fibromuscular
tissue
07.

VAGINA
vagina

⁕ Lapisan vagina terdiri dari mucosa, muscular

layer, dan adventitia
⁕ Epitel mukosa vagina→ Stratified squamous
dengan ketebalan 150-200 μm.
⁕ Mucosa mengandung lymphocyte and
neutrophils
⁕ Bakteri memetabolisme glikogen menjadi asam
laktat→ pH rendah untuk menjaga dari
pathogenic microorganisms
⁕ Muscular layer→ smooth muscle
⁕ Adventitia→ Jaringan ikat pada organ sekitarnya
08.

External
Genitalia
 External Genitalia / Vulva
→ stratified squamous epithelium

● Vestibule, includes tubuloacinar vestibular

gland
● Labia minora, numerous sebaceous glands
● Labia majora, homologous, similar to the skin of
the scrotum
● Clitoris, erectile structure homologous

Vulvar Pathology (pp.3-17)

Physiology
 01.
Female Physiology Before
Pregnancy and Female
Hormones
PHYSIOLOGIC ANATOMY OF THE FEMALE SEXUAL ORGANS

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PHYSIOLOGIC ANATOMY OF THE FEMALE SEXUAL ORGANS

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OOGENESIS AND FOLLICULAR DEVELOPMENT IN THE OVARIES

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OOGENESIS AND FOLLICULAR DEVELOPMENT IN THE OVARIES

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 FEMALE HORMONAL SYSTEM

● The female hormonal system three hierarchies of hormones:

○ The hypothalamic releasing hormone, called gonadotropin-releasing
hormone (GnRH)
○ The anterior pituitary sex hormones, follicle- stimulating hormone
(FSH) and luteinizing hormone (LH)
○ The ovarian hormones, estrogen and progesterone

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FEMALE HORMONAL SYSTEM

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 MONTHLY OVARIAN CYCLE AND FUNCTION OF GONADOTROPIC
HORMONES

● Also known as female monthly secual cycle or menstrual cycle

● The female sexual cycle has two significant results
○ First, only a single ovum is normally released from the ovaries each month
○ Second, the uterine endometrium is prepared in advance for implantation
of the fertilized ovum

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GONADOTROPIC HORMONES AND THEIR EFFECTS ON THE OVARIES

● In the absence of FSH and LH, the ovaries remain inactive

● At age 9 to 12 years, the pituitary begins to secrete progressively more FSH and
LH which leads to the onset of normal monthly sexual cycles beginning
between the ages of 11 and 15 years

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GONADOTROPIC HORMONES AND THEIR EFFECTS ON THE OVARIES

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 OVARIAN FOLLICLE GROWTH—THE FOLLICULAR PHASE OF THE
OVARIAN CYCLE

● When a female child is born, each ovum is surrounded by a single layer of

granulosa cells; the ovum, with this granulosa cell sheath, is called a primordial
follicle
● Then, after puberty, when FSH and LH from the anterior pituitary gland begin
to be secreted in significant quantities, the ovaries begin to grow.
● The first stage of follicular growth is moderate enlargement of the ovum, which
increases in diameter 2-fold to 3-fold
● That stage is followed by growth of additional layers of granulosa cells in some
of the follicles. These follicles are known as primary follicles.

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 Development of Antral and Vesicular Follicles.

● During the first few days of each monthly female sexual cycle, the
concentrations of FSH and LH secreted by the anterior pituitary gland increase
slightly to moderately
● These hormones, especially FSH, cause accelerated growth of 6 to 12 primary
follicles each month
● The initial effect is rapid proliferation of the granulosa cells, giving rise to many
more layers of these cells.
● In addition, spindle cells derived from the ovary interstitium collect in several
layers outside the granulosa cells, giving rise to a second mass of cells called
the theca.

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 Development of Antral and Vesicular Follicles.

● The theca is divided into two layers

○ The theca interna, the cells take on epithelioid characteristics similar to
those of the granulosa cells and develop the ability to secrete additional
steroid sex hormones
○ The theca externa, develops into a highly vascular connective tissue
capsule that becomes the capsule of the developing follicle.
● After the early proliferative phase of growth, the mass of granulosa cells
secretes a follicular fluid that contains a high concentration of estrogen
● Accumulation of this fluid causes an antrum to appear within the mass of
granulosa cells

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 Development of Antral and Vesicular Follicles.

● The early growth of the primary follicle up to the antral stage is stimulated
mainly by FSH alone.
● Greatly accelerated growth then occurs, leading to still larger follicles called
vesicular follicles.
● This accelerated growth is caused by the following mechanisms:
○ Estrogen is secreted into the follicle and causes the granulosa cells to
form increasing numbers of FSH receptors
○ The pituitary FSH and the estrogens combine to promote LH receptors on
the original granulosa cells
○ The increasing estrogens from the follicle plus the increasing LH from the
anterior pituitary gland act together to cause proliferation of the follicular
thecal cells and increase their secretion
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 Only One Follicle Fully Matures Each Month, and the Remainder Undergo
Atresia
● After a week or more of growth—but before ovulation occurs—one of the
follicles begins to outgrow all the others, and the remaining 5 to 11 developing
follicles involute (a process called atresia)
● Prevents more than one child from developing with each pregnancy

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 OVULATION

● Ovulation in a woman who has a normal 28-day female sexual cycle occurs 14
days after the onset of menstruation
● Shortly before ovulation, the protruding outer wall of the follicle swells rapidly,
and a small area in the center of the follicular capsule, called the stigma
● In another 30 minutes or so, fluid begins to ooze from the follicle through the
stigma, and about 2 minutes later, the stigma ruptures widely, allowing a
more viscous fluid
● This viscous fluid carries with it the ovum surrounded by a mass of several
thousand small granulosa cells, called the corona radiata.

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 A Surge of Luteinizing Hormone Is Necessary for Ovulation

● About 2 days before ovulation, the rate of secretion of LH by the anterior

pituitary gland increases markedly, rising 6- to 10-fold
● The LH also has a specific effect on the granulosa and theca cells, converting
them mainly to progesterone-secreting cells.
● It is in this environment of
○ Rapid growth of the follicle,
○ Diminishing estrogen secretion
○ Initiation of secretion of progesterone that ovulation occurs

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Initiation of Ovulation

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CORPUS LUTEUM—THE LUTEAL PHASE OF THE OVARIAN CYCLE

● During the first few hours after expulsion of the ovum from the follicle, the
remaining granulosa and theca interna cells change rapidly into lutein cells
● They enlarge in diameter two or more times and become filled with lipid
inclusions that give them a yellowish appearance.
● This process is called luteinization, and the total mass of cells together is called
the corpus luteum
● The granulosa cells in the corpus luteum develop extensive intracellular
smooth endoplasmic reticula that form large amounts of the female sex
hormones progesterone and estrogen
● The theca cells form mainly the androgens androstenedione and testosterone

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 Secretion by the Corpus Luteum: An Additional Function of Luteinizing
Hormone.
● The corpus luteum is a highly secretory organ, secreting large amounts of
progesterone and estrogen.
● the newly formed lutein cells go through a sequence of
○ (1) proliferation
○ (2) enlargement
○ (3) secretion
○ (4) degeneration

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 Involution of the Corpus Luteum and Onset of the Next Ovarian Cycle.

● Estrogen in particular and progesterone have strong feedback effects on the

anterior pituitary gland to maintain low secretory rates of FSH and LH.
● The lutein cells secrete small amounts of the hormone inhibin
● This hormone inhibits FSH secretion
● Low blood concentrations of FSH and LH result, and loss of these hormones
finally causes the corpus luteum to degenerate completely, a process called
involution

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 Involution of the Corpus Luteum and Onset of the Next Ovarian Cycle.

● Final involution normally occurs at the end of almost exactly 12 days of corpus
luteum life, which is around the 26th day of the normal female sexual cycle, 2
days before menstruation begins
● At this time, the sudden cessation of estrogen, progesterone, and inhibin
secretion by the corpus luteum removes the feedback inhibition of the anterior
pituitary gland, allowing it to begin secreting increasing amounts of FSH and
LH again
● FSH and LH initiate the growth of new follicles, beginning a new ovarian cycle
● The paucity of progesterone and estrogen secretion at this time also leads to
menstruation by the uterus

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 Involution of the Corpus Luteum and Onset of the Next Ovarian Cycle.

● About every 28 days, gonadotropic hormones from the anterior pituitary gland
cause 8 to 12 new follicles to begin to grow in the ovaries
● One of these follicles finally becomes “mature” and ovulates on the 14th day of
the cycle.
● During growth of the follicles, estrogen is mainly secreted.
● After ovulation, the secretory cells of the ovulating follicle develop into a
corpus luteum that secretes large quantities of progesterone and estrogen.
● After another 2 weeks, the corpus luteum degenerates, whereupon the ovarian
hormones estrogen and progesterone decrease greatly, and menstruation
begins.

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 FUNCTIONS OF OVARIAN HORMONES— ESTRADIOL (ESTROGEN)
AND PROGESTERONE

● The estrogens mainly promote proliferation and growth of specific cells in the
body that are responsible for development of most secondary sexual
characteristics of females.
● The progestins function mainly to prepare the uterus for pregnancy and the
breasts for lactation.

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 CHEMISTRY OF THE SEX HORMONES

Estrogen
● In the normal nonpregnant female, estrogens are secreted in significant
quantities only by the ovaries,
● During pregnancy, large quantities of estrogens are also secreted by the
placenta
● The principal estrogen secreted by the ovaries is β-estradiol.

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 CHEMISTRY OF THE SEX HORMONES

Progestin
● By far the most important of the progestins is progesterone
● In nonpregnant females, progesterone is usually secreted in significant
amounts only during the latter half of each ovarian cycle, when it is secreted
by the corpus luteum.
● Large amounts of progesterone are also secreted by the placenta during
pregnancy, especially after the fourth month of gestation.

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CHEMISTRY OF THE SEX HORMONES

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 CHEMISTRY OF THE SEX HORMONES

● They are all steroids

● They are synthesized in the ovaries mainly from cholesterol derived from the
blood but also to a slight extent from acetyl coenzyme A
● Estrogens and Progesterone Are Transported in the Blood Bound to Plasma
Proteins
● The liver conjugated estrogens to form glucuronides and sulfates, and about
one-fifth of these conjugated products is excreted in the bile; most of the
remainder is excreted in the urine.
● Diminished liver function actually increases the activity of estrogens in the
body, sometimes causing hyperestrinism.
● Within a few minutes after se- cretion, almost all the progesterone is degraded
to other steroids that have no progestational effec

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FUNCTIONS OF THE ESTROGENS—THEIR EFFECTS ON THE PRIMARY AND SECONDARY
FEMALE SEX CHARACTERISTICS

● A primary function of the estrogens is to cause cellular proliferation and

growth of the tissues of the sex organs
● At puberty, the quantity secreted increases 20-fold or more. At this time, the
female sex organs change from those of a child to those of an adult.
● Estrogens cause marked proliferation of the endometrial stroma and greatly
increased development of the endometrial glands in uterine endometrium
● They cause the glandular tissues of fallopian tube to proliferate, and they
cause the number of ciliated epithelial cells that line the fallopian tubes to
increase

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 Effect of Estrogens on the Breasts

● Estrogens cause
○ (1) Development of the stromal tissues of the breasts
○ (2) Growth of an extensive ductal system
○ (3) Deposition of fat in the breasts
● The estrogens initiate growth of the breasts and of the milk-producing
apparatus
● They are also responsible for the characteristic growth and external
appearance of the mature female breast

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 Effect of Estrogens on the Bones

● Estrogens inhibit osteoclastic activity in the bones and therefore stimulate

bone growth
● Estrogens also cause uniting of the epiphyses with the shafts of the long
bones.
● Osteoporosis of the Bones Caused by Estrogen Deficiency in Old Age
○ (1) increased osteoclastic activity in the bones
○ (2) decreased bone matrix
○ (3) decreased deposition of bone calcium and phosphate

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 Effect of Estrogens on Protein, Fat, Hair, Skin, and Electrolyte Balance

● Estrogens cause a slight increase in total body protein

● Estrogens increase the whole-body metabolic rate slightly
● Estrogens do not greatly affect hair distribution
● Estrogens cause the skin to develop a texture that is soft and usually smooth
● Estrogens cause sodium and water retention by the kidney tubules

Guyton 14th
 Functions of Progesterone
● Decreases the frequency and intensity of uterine contractions, thereby helping
to prevent expulsion of the implanted ovum.
● Promotes increased secretion by the mucosal lining of the fallopian tubes for
nutrition.
● Promotes development of the lobules and alveoli of the breasts, causing the
alveolar cells to proliferate, enlarge, and become secretory. But secreted only
stimulated by prolactin

Guyton 14th
 Proliferative phase
❏ The endometrial surface is re-epithelialized
within 4 to 7 days after.
❏ At ovulation, endometrium is 3 to 5 mm.
❏ Te endometrial glands, especially those of
the cervical region, secrete mucus align
themselves along the length of the cervical
canal, forming channels that help guide
sperm in the proper direction from the
vagina into the uterus
Secretory phase
❏ progesterone and estrogen together are
secreted in large quantities for development
of the endometrium
❏ about 1 week after ovulation, the
endometrium has a thickness of 5 to 6 mm
❏ once the ovum implants in the endometrium,
the trophoblastic cells digest the
endometrium and absorb the endometrial
stored substances

Menstrual phase
❏ If the ovum is not fertilized, about 2 days before the end of the monthly cycle, the
corpus luteum in the ovary involutes (endometrium to about 65 percent) and the
ovarian hormones (estrogens and progesterone) decrease to low levels
❏ The vasospasm, the decrease in nutrients to the endometrium, and the loss of
hormonal stimulation initiate necrosis in the endometrium, especially of the blood
vessels
❏ During normal menstruation, approximately 40 milliliters of blood and an
additional 35 milliliters of serous fluid are los
❏ Normallry nonclotting because of fibrinolysin, if blood is excessive maybe theres
clot but it is clinical evidence of uterine disease
Guyton 14th
Guyton 14th
 FEEDBACK OSCILLATION OF THE
HYPOTHALAMIC-PITUITARY-OVARIAN
SYSTEM
❏ Postovulatory secretion of the ovarian hormones and
depression of the pituitary gonadotropins.
Between ovulation and the beginning of menstruation,
the corpus luteum secretes large quantities of
progesterone and estrogen, as well as inhibin causing
suppression of FSH and LH
❏ Follicular growth phase.
At about the time that menstruation begins, pituitary
secretion of FSH begins to increase again, as much as
twofold; then, several days after menstruation begins,
LH secretion increases slightly as well.
❏ The preovulatory surge of LH and FSH causes ovulation.
The high level of estrogens at this time is believed to
cause a positive feedback stimulatory effect, which leads
to a large surge in the secretion of LH and, to a lesser
extent, FSH. Guyton 14th
 Puberty Menarche Menopause
Puberty means the onset means the beginning of The period during which
of adult sexual life. The the cycle of the cycle ceases and the
period of puberty is menstruation. female sex hormones
caused by a gradual diminish to almost none
increase in gonadotropic is called menopause
hormone secretion by
At about age 45 years,
the pituitary, beginning
only a few primordial
in about the eighth year
follicles remain to be
of life.
stimulated by FSH and
LH, the production of
estrogens by the ovaries
decreases as the number
of primordial follicles
approaches zero.

Guyton 14th
 Hormonal Suppression
It is not fully understood why administration of estrogen or progesterone prevents
the preovulatory surge of LH secretion. However, experimental work has suggested
that immediately before the surge occurs, a sudden depression of estrogen
secretion by the ovarian follicles probably occurs, which might be the necessary
signal that causes the subsequent feedback effect on the anterior pituitary that
leads to the LH surge. The administration of sex hormones (estrogens or
progesterone) could prevent the initial ovarian hormonal depression that might be
the initiating signal for ovulation.

Guyton 14th
 02.
Pregnancy
 Pregnancy

MATURATION AND FERTILIZATION OF THE OVUM

EARLY NUTRITION OF THE EMBRYO
PLACENTA
HORMONAL FACTORS IN PREGNANCY
PARTURITION

Guyton and Hall Textbook of Medical Physiology

 MATURATION AND FERTILIZATION OF THE OVUM

Ovarium

Primary oocyte before is released

from the ovarian divides by
meiosis and a first polar body is
expelled from the nucleus.
The primary oocyte then becomes
the secondary oocyte, leaves 23
unpaired chromosomes
 MATURATION AND FERTILIZATION OF THE OVUM
Fallopian Tube (Uterine Tube)

When ovulation occurs, the ovum, along with a hundred

or more attached granulosa cells that constitute the
corona radiata, is expelled directly into the peritoneal
cavity and must then enter one of the fallopian tubes
(also called uterine tubes) to reach the cavity of the
uterus
 MATURATION AND FERTILIZATION OF THE OVUM
Fallopian Tube (Uterine Tube)

Fertilization of the Ovum

● After the male ejaculates semen into the vagina during intercourse, a
few sperm are transported within 5 to 10 minutes upward from the
vagina and through the uterus and fallopian tubes to the ampullae
● In the ampulla, before a sperm can enter the ovum, however, it must
first penetrate the multiple layers of granulosa cells attached to the
outside of the ovum (the corona radiata) and then bind to and
penetrate the zona pellucida surrounding the ovum. → On entering
the ovum, its head swells to form a male pronucleus,
● Once a sperm has entered the ovum → oocyte divides again to form
the mature ovum (mature ovum still carries 23 unpaired
chromosomes, One of these known as the X chromosome.)
● 23 unpaired chromosomes of the male pronucleus and the 23
unpaired chromosomes of the female pronucleus → a complete
complement of 46 chromosomes the fertilized ovum or zygote
WHAT DETERMINES THE SEX OF THE FETUS THAT IS CREATED?
 MATURATION AND FERTILIZATION OF THE OVUM
Fallopian Tube (Uterine Tube) → Uterus

TRANSPORT OF THE FERTILIZED OVUM IN THE FALLOPIAN TUBE

● After fertilization has occurred, an additional

3 to 5 days is normally required for transport
of zygot through the remainder of the
fallopian tube into the cavity of the uterus.
● This delayed transport of the fertilized ovum
through the fallopian tube allows several
stages of cell (blastocyst) and enters the
uterus. During this time, the fallopian tube
secretory cells produce large quantities of
secretions used for nutrition of the
developing blastocyst.
 MATURATION AND FERTILIZATION OF THE OVUM
Uterus

IMPLANTATION OF THE BLASTOCYST IN THE

UTERUS
● Developing blastocyst usually remains in the uterine
cavity an additional 1 to 3 days before it implants in the
endometrium
● Implantation ordinarily occurs on about the 5-7 day after
ovulation.
● Implantation results from the action of trophoblast cells
that develop over the surface of the blastocyst. These
cells secrete proteolytic enzymes that digest and liquefy
the adjacent cells of the uterine endometrium.
 EARLY NUTRITION OF THE EMBRYO
● Progesterone effect on the uterine endometrium,
endometrial stromal cells into large swollen cells
containing extra quantities of glycogen, proteins,
lipids, and even some minerals necessary for
development of the conceptus
● Continued secretion of progesterone causes the
endometrial cells to swell further and to store even
more nutrients → These cells are now called
decidual cells, and the total mass of cells is called
the decidua.
● Trophoblast cells invade the decidua, digesting and
imbibing it, the stored nutrients in the decidua are
used by the embryo for growth and development
 PLACENTA

● While the trophoblastic cords from the

blastocyst are attaching to the uterus, blood
capillaries grow into the cords from the
vascular system of the newly forming
embryo.
● About 21 days after fertilization, blood also
begins to be pumped by the heart of the
human embryo.
● Simultaneously, blood sinuses supplied with
blood from the mother develop around the
outsides of the trophoblastic cords.
● The trophoblast cells send out more and
more projections, which become placental
villi into which fetal capillaries grow.
 Placenta

Fetus
Blood of the fetus flows through two umbilical
arteries, then into the capillaries of the villi,
and finally back through a single umbilical vein
into the fetus
Mother
mother’s blood flows from her uterine arteries
into large maternal sinuses that surround the
villi and then back into the uterine veins of the
mother
 Placenta
Diffusion of Oxygen Through the Placental
Membrane
The dissolved oxygen in the blood of the
large maternal sinuses passes into the fetal
blood by simple diffusion, driven by an
oxygen pressure gradient from the
mother’s blood to the fetus’s blood.
(Po2) of the mother’s blood in the placental
sinuses is about 50 mm Hg, and Po2 in the
fetal blood 30 mm Hg.
Diffusion of Foodstuffs Through the
Placental Membrane
Glucose, fatty acids, potassium,
sodium, and chloride ions
Diffusion of Carbon Dioxide Through the
Placental Membrane
The partial pressure of carbon dioxide
(Pco2) of the fetal blood is 2 to 3 mm Hg
higher than that of the maternal blood →
allow adequate diffusion of carbon
dioxide
Excretion of Waste Products Through the
Placental Membrane.
urea, uric acid, and creatinine.
Higher concentrations of the excretory
products in the fetal blood than in the maternal
blood, there is continual diffusion of these
substances from the fetal blood to the maternal
blood.
 HORMONAL FACTOR IN PREGNANCY
Human chorionic gonadotropin Estrogen Progesterone

Secreted by the syncytial Secreted by the ● Progesterone causes decidual

trophoblast cells syncytial trophoblast cells to develop in the uterine
Function cells of the placenta. endometrium.
● Prevent involution of the ● Enlargement of the ● Progesterone decreases
corpus luteum at the end mother’s uterus, contractility of the pregnant
of the monthly female ● Enlargement of the uterus,
sexual cycle. mother’s breasts ● Progesterone contributes to
● Causes the corpus and growth of the development of the conceptus
luteum to secrete even breast ductal even before implantation
larger quantities of its structure, ● The progesterone secreted
sex hormones for the ● Enlargement of the during pregnancy helps
next few months. mother’s female estrogen prepare the mother’s
● Stimulates the Male Fetal external genitalia breasts for lactation,
Testes to Produce
Testosterone.
Human chorionic somatomammotropin
HORMONAL FACTOR IN PREGNANCY
 PARTURITION

Parturition means birth of the baby

Toward the end of pregnancy, the uterus becomes progressively
develops such strong rhythmic contractions that the baby is expelled.
1. Progressive hormonal changes that cause increased
excitability of the uterine musculature
2. Progressive mechanical changes
 Parturition
Hormonal Factors That Increase Uterine Mechanical Factors That Increase Uterine
Contractility Contractility

● Increased Ratio of Estrogens ● Stretch of the Uterine

to Progesterone Musculature
● Oxytocin Causes Contraction ● Stretch or Irritation of the
of the Uterus. Cervix.
● Effect of Fetal Hormones on
the Uterus
 ONSET OF LABOR
Positive feedback theory
● During pregnancy, the uterus undergoes periodic
episodes of weak and slow rhythmic contractions
called Braxton Hicks contractions
● These contractions are usually not felt until the
second or third trimester and become
progressively stronger toward the end of
pregnancy; then they change suddenly, within
hours, to become exceptionally strong
contractions that start stretching the cervix and
later force the baby through the birth canal.

2 types of positive feedback increase uterine contractions

1. stretching of the cervix → the entire body of the uterus
contract, → stretches the cervix even more because of
the downward thrust of the baby’s head,
2. cervical stretching → the pituitary gland to secrete
oxytocin → increasing uterine contractility.
ABDOMINAL MUSCLE CONTRACTIONS DURING LABOR

Once uterine contractions become strong during labor → pain signals

originate both from the uterus and from the birth canal → causing
suffering, and occurs neurogenic reflexes in the spinal cord to the
abdominal muscles, → causing intense contractions of these muscles.
The abdominal contractions add greatly to the force that causes expulsion
of the baby
 Mechanics of Parturition
The uterine contractions during labor begin mainly at the top of the uterine fundus and spread
downward over the body of the uterus, force the baby downward toward the cervix.

Early part of labor, the contractions might occur only once every 30 minutes. As labor progresses, the
contractions finally appear as often as once every 1 to 3 minutes and the intensity of contraction
increases greatly, with only a short period of relaxation between contractions

The head acts as a wedge to open the structures of the birth canal as the fetus is forced downward.
The first major obstruction to expulsion of the fetus is the uterine cervix.
first stage of labor is a period of progressive cervical dilation, lasting until the cervical opening is as
large as the head of the fetus.

Once the cervix has dilated fully, the fetal membranes usually rupture and the amniotic fluid is lost
suddenly through the vagina. Then the head of the fetus moves rapidly into the birth canal, until
delivery occurs. This is called the second stage of labor.
 Separation and Delivery of the Placenta

For 10 to 45 minutes after birth of the baby, the uterus continues to contract to a smaller and
smaller size, which causes a shearing effect between the walls of the uterus and the placenta,
thus separating the placenta from its implantation site. Separation of the placenta opens the
placental sinuses and causes bleeding.

Labor Pains
During the second stage of labor, when the fetus is being expelled through the birth canal, much
more severe pain is caused by cervical stretching, perineal stretching, and stretching or tearing
of structures in the vaginal canal. This pain is conducted to the mother’s spinal cord and brain by
somatic nerves.

Involution of the Uterus After Parturition

During the first 4 to 5 weeks after parturition, the uterus involutes.During early involution of the
uterus, the placental site on the endometrial surface autolyzes, causing a vaginal discharge known
as lochia, which is first bloody and then serous in nature and continues for a total of about 10 days
Embryology
 THE CHROMOSOME THEORY OF
INHERITANCE

Mitosis
Mitosis is the process whereby one cell divides,
giving rise to two daughter cells that are
genetically identical to the parent cell

Langman’s Medical Embryology

 THE CHROMOSOME THEORY OF
INHERITANCE
Meiosis
Meiosis is the cell division that takes
place in the germ cells to generate male
and female gametes, sperm and egg cells,
respectively. Meiosis requires two cell
divisions, meiosis I and meiosis II, to
reduce the number of chromosomes to
the haploid number of 23

Langman’s Medical Embryology

 MORPHOLOGICAL CHANGES DURING MATURATION
OF THE GAMETES
Maturation of Oocytes Begins Before Birth
 Maturation of Oocytes Continues at Puberty

● Menjelang Kelahiran → Oosit Primer → memulai tahap Profase Meiosis I ⇒ Tahap Diploten →
tahapan istirahat selama proses profase yang ditandai dengan adanya Lacy network of chromatin
○ Tahap Meiosis I tidak berlanjut → Oocyte maturation inhibitor (OMI) → Peptide yang
berukuran kecil yang disekresi oleh sel folikular
■ Pada masa kanak-kanak,beberapa oosit → Atresia
■ Pada awal pubertas → jumlahnya sekitar 40.000
■ Pada saat proses ovulasi jumlahnya sekitar 500
❖ Antrum → suatu rongga untuk folikel menyimpan cairan & akan masuk ke
tahap antral/vesicular
❖ Folikel vesikular matur (Graff) → proses cairan terus
berakumulasi,sehingga sesaat sebelum ovulasi → folikel cukup membesar
➢ Folikel vesikular matur (Graff) → berdiameter 25mm/lebih →
dikelilingi juga oleh teka interna, yang terdiri dari sel-sel yang dapat
mensekresi steroid,kaya pembuluh darah,dan teka eksterna →
bersatu dengan jaringan ikat ovarium
➢ Tahap antral → tahap terlama
➢ Tahap vesikular matur (folikel graff) → berlangsung hanya sekitar
37 jam sebelum ovulasi

● Pada saat folikel primordial mulai berkembang, sel-sel folikular sekitarnya

akan berubah bentuk yang pada awalnya gepeng → kuboid,kemudian
berproliferasi menghasilkan sel granulosa berlapis → folikel primer
○ Teka folikuli → sel granulosa yang letaknya pada membran basalis
→ batasan dari jaringan ikat ovarium (sel stroma) disekelilingnya
○ Zona pelusida → terbentuk dari sel-sel granulosa dan oosit yang
mensekresi lapisan glikoprotein pada permukaan oosit
○ Pada proses pertumbuhan folikel,sel-sel teka folikuli tersusun dan
akan membentuk lapisan bagian dalam sel-sel sekretorik → teka
interna
○ Kapsul fibrosa yang terletak dibagian luar → teka eksterna
○ Kumulus ooforus
 Spermatogenesis
Maturation of Sperm Begins at Puberty
★ Pada saat seseorang memasuki fase pubertas → Proses Spermatogenesis dimulai, Spermatogonia →
spermatozoa
★ Saat seseorang bayi laki-laki lahir → sel germinativum terdapat didalam korda seks testis → sel-sel pucat
besar dikelilingi oleh sel penunjang → berasal dari epitel permukaan testis,prosesnya sama dengan sel folikular
→ Sel sustentakular/Sel Sertoli
➢ Sebelum masuk ke fase pubertas → korda seks akan membentuk lumen → tubulus seminiferus
➢ Pada interval yang signifikan → sel-sel mulai muncul dari populasi sel punca → Spermatogonia tipe A →
yang menjadi tanda proses Spermatogenesis
○ Pembelahan sel yang terakhir akan membentuk Spermatogonia tipe B → Spermatosit primer
■ Memasuki tahap profase (22 hari), yang kemudian diikuti oleh proses Meiosis I dengan cepat
dan akan membentuk → Spermatosit sekunder
■ Pada tahap Meiosis II → mulai membentuk Spermatid haploid
➢ Proses spermatogenesis diatur oleh produksi hormon LH
oleh kelenjar hipofisis → berikatan dengan Sel-sel Sertoli →
untuk proses Spermatogenesis
➢ FSH (Follicle-stimulating hormone) → juga berperan karena
berikatan dengan Sel-sel sertoli yang dapat merangsang
produksi cairan testis dan sintesis protein reseptor androgen
intraselular
 Spermiogenesis
➔ Suatu proses yang berperan dalam proses pembentukan Spermatid → Spermatozoa
❖ Proses yang terjadi pada Spermiogenesis :
1. Pembentukan akrosom → menutupi sebagian permukaan nukleus & mengandung enzim-enzim untuk
penetrasi pada telur & lapisan-lapisan yang melapisi selama proses fertilisasi
2. Kondensasi nukleus
3. Pembentukan leher bagian tengah & ekor
4. Perataan sebagian besar Sitoplasma → badan residu difagositosis oleh Sel-sel Sertoli
★ Membutuhkan waktu → sekitar 74 hari → Spermatogonium → Spermatozoa matur
★ Setiap hari → kurang lebih 300 juta sperma yang diproduksi
★ Setelah terbentuk sempurna → Spermatozoa akan masuk ke lumen tubulus seminiferus → akan masuk ke
epididimis oleh elemen kontraktil yang terdapat pada dinding seminiferus
○ Spermatozoa mendapatkan motilitasnya di dalam epididimis
THANKS
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