Patofyziologie reprodukce – Ústav patologické fyziologie LF MU1
Pathophysiology of reproduction
Julie Dobrovolná
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Revision
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Pathophysiology of pregnancy
Fetoplacental unit
Fetoplacental unit:
- consists of placenta, fetal adrenal gland and fetal liver. In this unit, the fetal adrenal gland is
the primary source of dehydroepiandrosterone. It is further metabolized by the fetal liver and
placenta to a wide range of estrogens.
There are several diseases that can affect the fetal and maternal adrenal glands during pregnancy.
Most often, it is steroid 21-hydroxylase deficiency, which leads to abnormalities in sexual
development and may even endanger the life of the newborn.
Pregnancy is marked by accretions in several endocrine systems, particularly the reninangiotensin-aldosterone
system and the hypothalamus-pituitary-adrenal system.
Maternal abnormalities are associated with a significant risk of maternal morbidity and mortality.
Fortunately, they are rare.
https://embryology.med.unsw.edu.au/embryology/index.php/
https://embryology.med.unsw.edu.au/embryology/index.php/
Implantation
5-12 days after conception
Trophoblast grows and spreads
Maternal blood freely circulating in lacunes
Gastrulation
Embryonic target consists of:
Endoderm
Mesoderm
Ektoderm
https://embryology.med.unsw.edu.au/embryology/index.php/
Internal cellular mass and gastrulation
https://embryology.med.unsw.edu.au/embryology/index.php/
Extraembryonic membranes
https://embryology.med.unsw.edu.au/embryology/index.php/
Placental development
https://embryology.med.unsw.edu.au/embryology/index.php/
Embryo anatomy
Yolk sac
Where blood cells are produced
Amnion
Encompasses the fluid around embryo
Allantois
Bladder
Chorion
https://embryology.med.unsw.edu.au/embryology/index.php/
Characteristic features of feto-placental circulation
• Parallel arrangement of two arterial systems and corresponding
chambers
• Mixed venous return and preferential blood flow.
• High resistance and low real circulation in lung circuit
• Low resistance and high-flow circulation in placenta.
• Shunt presence (3 shunts
- Ductus venosus
- Foramen ovale
- Ductus arteriosus
https://embryology.med.unsw.edu.au/embryology/index.php/
Source: http://www.colorado.edu/intphys/Class/IPHY3430-200/image/18-12.jpg
https://embryology.med.unsw.edu.au/embryology/index.php/
Fetal blood flow I
When oxygenated blood from the mother
enters the right side of the heart it flows
into the upper chamber (the right atrium).
Most of the blood flows across to the left
atrium through a shunt called the
foramen ovale.
From the left atrium, blood moves down
into the lower chamber of the heart (the
left ventricle). It's then pumped into the
first part of the large artery coming from
the heart (the ascending aorta).
From the aorta, the oxygen-rich blood is
sent to the brain and to the heart muscle
itself. Blood is also sent to the lower
body.
https://embryology.med.unsw.edu.au/embryology/index.php/
Fetal blood flow II
Blood returning to the heart from the fetal body
contains carbon dioxide and waste products as
it enters the right atrium. It flows down into the
right ventricle, where it normally would be sent
to the lungs to be oxygenated. Instead, it
bypasses the lungs and flows through the
ductus arteriosus into the descending aorta,
which connects to the umbilical arteries. From
there, blood flows back into the placenta. There
the carbon dioxide and waste products are
released into the mother's circulatory system.
Oxygen and nutrients from the mother's blood
are transferred across the placenta. Then the
cycle starts again.
https://embryology.med.unsw.edu.au/embryology/index.php/
Fetal blood flow III
At birth, major changes take
place. The umbilical cord is
clamped and the baby no
longer receives oxygen and
nutrients from the mother. With
the first breaths of air, the
lungs start to expand, and the
ductus arteriosus and the
foramen ovale both close. The
baby's circulation and blood
flow through the heart now
function like an adult's.
https://embryology.med.unsw.edu.au/embryology/index.php/
Uzávěr shuntů
Pathophysiology of preterm birth
26
Pathophysiology of premature birth II
27
Waking up too early – the consequences of preterm birth on sleep development
Laura Bennet David W. Walker Rosemary S. C. Horne First published: 24 April 2018
https://doi.org/10.1113/JP274950
Pathophysiology of premature birth III
28
Low Birth Weight and Adverse Perinatal Outcomes
•November 2019 DOI: 10.5772/intechopen.89049
Pathophysiology of pre-eclampsia
29
Elizabeth Phipps, Devika Prasanna,
Wunnie Brima and Belinda Jim
CJASN June 2016, 11 (6) 1102-1113; DOI:
https://doi.org/10.2215/CJN.12081115
Pathophysiology of pre-eclampsia - II
Lina Bergman, Cerebral biomarkers in women with
preeclampsia
October 2017 DOI: 10.13140/RG.2.2.30083.81445
30
Aspirin in the prevention of preeclampsia: the conundrum of how, who and when.
Shanmugalingam R, Hennessy A, Makris A.
J Hum Hypertens. 2019 Jan;33(1):1-9. doi: 10.1038/s41371-018-0113-7.
Patophysiology of subfertility – female
factors
31
Pathophysiology of subfertility – male
factors
32
The role of adipose tissue in reproduction
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34
HEART
KIDNEY
VASA SKELETAL MUSCLE
PANKREAS
LIVER
INFLAMMATION
HYPERTROP
HY OF
ADIPOSE
TISSUE
CARDIOVASCULAR
SYSTEM – BLOOD
CLOTTING,
FIBRINOLYSIS,
ANTICOAGULATION
INSULIN SENSITIVITY
LEPTIN
APN
APELIN
TNF-α
PAI-1
AGT
APN
APELIN
LEPTIN
APN
APELIN RBP-4?
IL-6?
TNF-α
VISFATIN
APN
Adipokines
̶ Terminology overlap with cytokines, also referred to as „adipocytokines“:
̶ sensu stricto definition: „cytokines produced in WAT“
̶ sensu lato: „various substances, including cytokines and hormones, produced in WAT“
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White adipose tissue (WAT)
Adipokines in development of trophoblast
Tersigni C. Obstet Gynecol Survey 2011
Ramsay, J. E et al. BMJ 2006
Adipokines, obesity and female fertility
Serum levels of leptin as function of % body fat
Considine RV. N Engl J Med 1996
Hammoud A. Fertil Steril 2008
Adipokines in male fertility
What else? Sugar?
Fetal programming?
Fetal programming
Fetal metabolic programming and epigenetic modifications: a systems
biology approach Silvia Sookoian, Tomas Fernández Gianotti, Adriana L. Burgueño &
Carlos J. Pirola Pediatric Research volume 73, pages531–542(2013)
Developmental plasticity
Ancient origins of human developmental plasticity.
Crespi EJ, Denver RJ.
Am J Hum Biol. 2005 Jan-Feb;17(1):44-54.
Braam B et al. (2007) Technology Insight: innovative options for end-stage renal disease—from kidney refurbishment to
artificial kidney Nat Clin Pract Nephrol 3: 564–572 doi:10.1038/ncpneph0600
Developmental plasticity in time
Developmental plasticity?
Reprogramming normal
human epithelial
tissues to a common,
lethal neuroendocrine
cancer lineage
1.Jung Wook Park1,
2.John K. Lee2,
3.Katherine M. Sheu3,
4.Liang Wang1,
5.Nikolas G. Balanis3,
6.Kim Nguyen4,
7.Bryan A. Smith1,
8.Chen Cheng5,
9.Brandon L. Tsai1,
10.Donghui Cheng1,
11.Jiaoti Huang6,
12.Siavash K.
Kurdistani5,7,8,9,
13.Thomas G.
Graeber3,7,8,9,10,*,
14.Owen N. Witte1,3,7,8,9,*
See all authors and
affiliations
Science 05 Oct 2018:
Hochberg Z et al. Endocrine Reviews 2011;32:159-224
©2011 by Endocrine Society
Environmental factors Programming
Health Outcomes later in life
➢ Ischemic heart disease
➢ Diabetes mellitus
➢ Obesit
➢ Hypertension
➢ Cancer
➢ Mental health problems
Conflict with
postnatal
environment
Epigenomic changes Permanent changes
in gene expression
Influence on phenotype later
in life
Ac
CH3
CH3
Ac
CH3
CH3
CH3
CH3
CH3
Ac Ac
Ac
CH3
Nutrition Maternal
health
Stress
Lifestyle
Placenta
DOHAD – Developmental Origins of Health and Disease
Thank you for attention,
Vasku.julie@seznam.cz