The female reproductive system III:

Fertilization, the placenta and mammary glands

Dr. Louis Toth – Fall 2006ljtoth@bu.edu

With Kind Regards

This Article has been uploaded for the benefit of the students.

We have Reproduced it in its original form with out any change.

We are highly thankful to the original author and extend our kind Regards

Prof.M.C. Bansal Prof Veena Acharya

Fertilization requires …

…penetration of cervical mucus

…capacitation

…penetration of corona radiata (for which capacitation is necessary)

… dissolution of zona pellucida-Sperm receptor-Acrosomal reaction

… penetrating the egg’s plasma membrane- sperm-egg adhesion

Age and fertility

Infertility is a normal consequence of aging

Completion of meiosis

Sperm entry triggers completion of metaphase II

Second polar body is producedMale and female pronuclei form

Pronuclei fuse, 2n is restored

(first polar body – may or may not still be with the oocyte)

second polar body

Ovum (proper)

Zygote (proper)

Secondary oocyte

Definitions

Oogonium (“egg seed”) – precursor of the female gamete, in the fetal ovary

Oocyte (“egg cell”) – female gamete while undergoing meiosis

Ovum (“egg”) – properly, the mature, post-meiotic female gamete, but more generally the female gamete at any stage of maturation.

Zygote (“yoked”) – properly, the fertilized ovum after male and female pronuclei have fused, but more generally, the fertilized oocyte.

Morula (“mulberry”) - mass of blastomeres resulting from first few divisions of the zygote

Blastula (“little bud”) – blastomeres arranged as a hollow sphere

Fertilized ovum ( = “zygote”)

polar bodies

diploid (2n) nucleus

zona pellucida

Embryogenesis: Cleavage stages

Early cleavage: 2 cell stage

blastomeres

Day 1 PF

Total volume remains constant

Day 2 PF

Early cleavage: 4 cell stage

Day 3 PF

Early cleavage: 8 cell stage

Last stage at which the cells are totipotent: each is capable of making an entire embryo

Morula stage: 12-16 cells

Day 4 PF

At this stage, one cell can be removed for PCR and genetic testing

A way around the US government ban on stem-cell research?

Nature 442, 24 August 2006

Blastocyst stage

Day 6 PF

trophoblast

inner cell mass

Day 6 PF

Blastocyst stage

morula

ovary

blastocyst

uterus

Transport to uterus

|||||||||||||___________________________________________________________________|<--menstrual-->|<--------- proliferative ------->|<-----------|----- secretory -----|------->|1 5 15 20 25 28

|-ovul.-| |<--implantation-->|

day:

The implantation window

Day

5 P

F

Day

9 P

F

Fer

tiliz

atio

n

Implantation – day 6/7 PF

DAY 7 PF

• The part of the trophoblast which overlies the ICM contacts the endometrium

Implantation – day 8/9 PF

• the trophoblast differentiates into two layers:

• cytotrophoblast: a mitotically active cellular layer which gives rise to the…

• syncytiotrophoblast: a syncytium which grows as cells fuse into it and actively invades the endometrium

• The trophoblast rapidly begins to invade the endometriium

• By day 11 PF, the conceptus is completely embedded in the endometrium

The inner cell mass differentiates into ectoderm, mesoderm and endoderm which give rise to all tissues of the embryo

Implantation – day 10/11 PF

Ectodermepidermis, brain, nervous system

MesodermNotochordSomites

muscle, serosa, excretory system, gonadsMesenchyme

dermis, bones, cartilage, circulatory system

Endodermgut, digestive tract, respiratory tractliver, pancreas, glands

Yolkgerm cells

Embryonic origin of tissues

• Blood from the spiral arteries empties into lacunae in the syncytiotrophoblast

• The syncytiotrophoblast secretes:• human chorionic gonadotrophin (hCG)• hum. chor. somatomammotropin (hCS)• estrogens• progesterone• enzymes• prostaglandins• growth factors

Spiral arteries

Uterine glands

Implantation – day 14 PF

• The chorion, an extra-embryonic membrane surrounding the embryo, begins to send out villi into the lacunae

hCG in placenta

www-medlib.med.utah.edu

Relation of placenta

and embryo

www-medlib.med.utah.edu

Rat embryo: Comparative Placentation, K. Benirschke, UCSD

PlacentaAmnionic side

decidual platecotyledonsanchoring villi

umbilical cordamnionic sacchorionic plate

Chorionic side

20 weekembryo

Cotyledonsvisualized byinjection casting

• EMBRYONIC TISSUE IS DERIVED FROM THE TROPHOBLAST

AMNION AND CHORIONVILLIDECIDUAL PLATEEXTRACHORIONIC

TROPHOBLAST

• MATERNAL TISSUE IS DERIVED FROM THE ENDOMETRIUM

decidual cellsspiral arteries

Placenta and decidua deciduabasalis

deciduaparietalis

deciduacapsularis

Terms:gravid = pregnantdecidua = gravid endometrium

Functions of the placenta:• Exchange oxygen from the mother for carbon dioxide from the fetus

• Exchange nutrients from the mother for wastes from the fetus

• Exchange hormones between the fetus and the mother

• Carry antibodies from the mother to the fetus

• Promote the maternal blood supply by enlarging the diameter of the spiral arteries

Twins and twin placentas(IDENTICAL) (FRATERNAL)

Changes in the decidua

Two types of cells target spiral arteries

Decidual cells……derive from mother…respond to progesterone…have myofibroblast properties…prevent trophoblastic invasion

-Extrachorionic trophoblast cells……derive from placenta…fuse with spiral arteries…expand the blood supply

Placental growth

basal plate

chorionic plate22 days

31 days

60 days

Bloom & Fawcett 1986

• stem villus - grows directly from the chorionic plate

• branch villus – grows as an offshoot of a stem villus

• anchoring villus - grows across the lacuna and contact the decidua basalis

• free villus - ends in the lacunae

Describing villi

basal plate

chorionic plate

Pre-eclampsia…… is diagnosed by maternal high

blood pressure and proteinuria.

… correlates with the failure of spiral arteries to enlarge upon contact with placenta.

… might have an immunological component (fetal material in the maternal circulation?).

… has lack of free placental villi as a postpartum finding.

… Can only be treated by delivery of the fetus, but Viagra is in Phase II trials.

Normal 40wk placental villi

Pre-eclampsia 37wk placental villi

Picture credits: Benirshke, Kaufman Pathology of the Human Placenta 2nd ed.

Primary villus: core of cytotrophoblast cells surrounded by a syncytiotrophoblast shell

Secondary villus: core of mesenchyme grows into the center

Tertiary villus: capillaries grow into the mesenchyme

Chorionic plate

Decidual plate

Gray’s Anat. (Fetus)

(Mom)

Temporal development of villi

Chorionic villi in an early placenta

Secondary villi

Mature (tertiary) Chorionic villi• prevents direct contact between maternal and fetal blood

•CO2, O2, fatty acids, electrolytes, etc. cross by diffusion

• amino acids, antibodies, etc. are actively transported

Syncitial knots

Cells:Syncitiotrophoblast layerCytotrophoblast cellsHofbauer cells (macrophages)Endothelial cells

The blood-placental barrier

• prevents direct contact between maternal and fetal blood

•CO2, O2, fatty acids, electrolytes, etc. cross by diffusion

• amino acids, antibodies, etc. are actively transported

• Rh factor incompatibility

+ = , ,Ab Ab

Rh- mom Rh+ dad

AbAb

Blood doesn’t cross placenta Ab crosses placenta

1st child 2nd child

Fetal Alcohol Syndrome

www.fetalalcohol.com

Diagnosis is based on:Characteristic featuresGrowth retardationCNS abnormalities

Timing of maternal alcohol consumption plays a role.

Alcohol stays longer and achieves higher concentration in fetal circulation, compared to mother.

Mammary glands

Modified sweat glandsProduce milk after

childbirth

Adipose tissueSecretory acini

lobes & lobulesLactiferous ducts

lactiferous sinus intralobular duct interlobular duct

Alveoli

Intra-lobula

r duct

Production of Milk

prolactin

oxytocin

Suckling reflexnipple → hypothalamuscan be conditioned (e.g. to crying)+prolactin: causes production of milk+oxytocin: causes ejection of milk, ‘letdown’inhibition of GnRH inhibits ovulation

Ambrogio Lorenzetti, Siena

Mammary Gland

Inactive Pregnant Lactating

Colostrum

• produced during pregnancy and immediately after birth

• high in protein; lower in lipid than milk

• contains antibodies for passive protection of the newborn

• contains growth factors (PDGF, EGF, IGF-1)

• continuously changes in composition

•changes to milk within a few days of initiation breastfeeding

www.westerndairyscience.com

Colostrum

Lipids Proteins Carbohydrates Antibodies

Milk

• produced during pregnancy and immediately after birth

• high in protein; lower in lipid than milk

• contains antibodies for passive protection of the newborn

• contains growth factors (PDGF, EGF, IGF-1)

• continuously changes in composition

•changes to milk within a few days of initiation breastfeeding

• Vitamins• Hormones• Salts

proteinscarbs

lipids

Secreted Components of Milk

• Proteins and carbohydrates are synthesized by alveolar cells and secreted by merocrine secretion into the lumen

• Lipids are synthesized by the alveolar cells and secreted by apocrine secretion into the lumen

• vitamins, salts and hormones migrate from interstitial blood vessels through alveolar cells into the lumen

Transported Components of Milk

IgA

Transcytosed Components of Milk

IgA

IgA

IgA

IgA

• Antibodies (IgA) are synthesized by plasma cells in the interstitium and transcytosed across the alveolar cells into the lumen

Breast Cancers

Second most frequent cause of cancer deaths in US

Affects 1:8 women Ductal (80%) Lobular (10%) Infiltrating carcinoma breaches

basement membrane, metastasizes to lymphatic nodes

Tamoxifen (anti-estrogen) is drug of choice

BRCA1 & BRCA2 tumor suppressor genes are involved in familial breast and ovarian cancers

25 30 50 80

1:20000 1:2500 1:50 1:10

age

incidence

Mammography

McGill Univ. Molson Medical Informatics ProjectInteractive Mammograpgy Analysis Web TutorialJames Nguyen ’02 , David Fleiszer, MDhttp://sprojects.mmi.mcgill.ca/dir/mammography.html

http://medstat.med.utah.edu/WebPath/

fin.