Fetal to Neonatal Transition extrauterine

Fetal-to-Neonatal-Transition.ppt

1. Fetal to Neonatal Transition
Adjusting to Extra-Uterine Life

2. Cardiovascular Function
•Ductus Arteriosis –Duct between Pulmonary
Artery and Aorta that allows most blood to be
shunted past the Pulmonary Artery and into
Aorta. With increase in pO2 at birth, the Ductus
Arteriosis closes and blood is forced to go to
the lungs for oxygenation.
•Foramen Ovale –Valve (flap-type) that closes
when pressure in left side of heart increases
upon closure of the Ductus Arteriosis.

3. ADULT
RIGHT HEART ►LUNGS ►LEFT HEART
↑ ↓ AORTA
↑
LIVER← ← ← BODY
FETUS
RIGHT HEART ►FORAMEN OVALE ►LEFT HEART
↑
↑ AORTA
DUCTUS ARTERIOSIS
PLACENTA BODY OF FETUS
Lung
Liver
Ductus
Venosus

4. Gut
•Filled with Amniotic Fluid drunk at 500 ml/day
•Contains meconium –fecal material
•Absorbs amino acids, sugars and electrolytes
•Digestion of proteins, aborption of amino acids and
incorporation into fetal tissues
•Colostrum –fluid phase pinocytosis and gut closure
regarding absorption of immunoglobulins
–Passive Immunity –required for piglets and beneficial for
offspring of all species
–Gut maturation
•IGF-I and EGF in colostrum stimulate gut maturation

5. Renal System
•Normal fetus –450 ml urine/day into
amniotic sac with turnover of 300 to 600
ml/h of amnionic fluid
•Proteinuria in fetal life to closure of kidney
tubules in neonate
•Absence or malfunction of kidneys leads
to death or retarded development

7. Respiratory System
•Fetal breathing occurs in utero
•Allows development of intercostal muscles of
chest and diaphragm associated with breathing

8. Endocrine System
•Decapitated fetal pigs and lambs grow
normally in utero due to fetal (IGF-I and IGF-II
from all tissues) and placental hormones and
growth factors
•Maternal hormones not transported across the
placenta except for some steroids
•Fetal-Placental Hormones Do Affect Maternal
System

9. Endocrine System
•Fetal-Placental Hormones Do Affect Maternal
System
–Quieting effect on nervous system
•Progesterone
•Opiods –endorphins, enkephalins, dynorphins
–Increase in cardiac output
–Peripheral vasodilation
–Increase renal clearance
–Altered glucose, fat, protein and mineral
metabolism to accommodate needs of fetal-
placental tissue growth

10. MATERNAL METABOLISM
–Nutritional Priorities of Fetus and Mother
•Maternal
–Nervous System
–Bone
–Muscle
–Fat
Fetal Demands
Nervous System
Bone
Muscle
Fat

11. Complete Inanition in Sows
•Water only: Days 0-40, 30 to 70 or 70 to 110
–No effect on fetal weight at birth
–Rapid realimentation of sows caused abortion
–Model for nutrient partitioning
–Animal welfare concerns
–Study done by Lloyd Anderson, Iowa State University 9 Am
J Physiol. 1979 Sep;237(3):E273-8.
–PMID: 474753 [PubMed -indexed for MEDLINE]
–4: Anderson LL, Hard DL, Kertiles LP. Related Articles,
Links
–Progesterone secretion and fetal development during
prolonged starvation in the pig. Am J Physiol. 1979
237(3):E273-8; Am J Physiol. 1979 236(4):E335-41; Am J
Physiol. 1978 234(2):E190-6.

12. Thyroid Function
•Thyroxin (T4) and triiodothyronine (T3)
required for normal development of brain,
bones, hair/wool

13. Pancrease
•Insulin regulates glucose metabolism by
fetus
•Diabetic mother –leads to more glucose
transport to fetal-placental tissue and
increased (insulin dependent) storage of
energy as glycogen and/or fat

14. Fetal Adrenal Glands
•Norepinephrine
–Release of surfactant from epithelial cells of lung lobulo-
alveolar structures
–Absorption of liquid from lungs
•Glucocorticoids (Cortisol and Corticosterone)
–Lung maturation
–Lactogenesis
–Thyroxin to Triiodothyronine
–Glucose storage as glycogen
–Insulin secretion in response to glucose
–Transition from fetal hemoglobin to adult hemoglobin
–Closure of Ductus Arteriosis
–Parturition

15. Lung Maturation
•Synthesis and secretion of surfactantby lung
alveolar epithelium
–Glucocorticoids –Synthesis (Transcription and
Translation) of surfactant and storage in cells
–Norepinephrine –Secretion of surfactant
•Surfactant essential for lung alveoli to
maintain integrity and not collapse by
providing high surface tension when stretched.
•Fetuses deficient in surfactant develop Hyalin
Membrane Disease and often die
•Now Pediatricians have artificial surfactant to
decrease risk of Hyalin Membrane Disease

16. Respiration
•Umbilical Circulation
–pO2
•Artery –15
•Vein-25
–pCO2
•Artery –55
•Vein –40
•Maternal Uterine Circulation
–pO2
•Artery –95
•Vein –35
–pCO2
•Artery –35
•Vein -45

18. Factors Affecting Reproductive
Efficiency
OVULATION RATE
FERTILIZATION RATE
EMBRYONIC SURVIVAL
UTERINE CAPACITY

19. OVULATION RATE
FERTILIZATION RATE
EMBRYONIC DEATHS
UTERINE CAPACITY
FACTORS AFFECTING REPRODUCTIVE
PERFORMANCE

20. OVULATION RATE
•HORMONAL REGULATION
–eCG
–FSH
•NUTRITION
–Ad Libitum Feeding
•Swine –14 days prior to estrus increases ovulation rate
about 30%
•Sheep –Improved pasture or feed prior to onset of
breeding season

21. OVULATION RATE (continued)
•GENETIC SELECTION
–Boorola Merino
•Single gene mutation to decrease inhibin
•Ovulation rates –3 to 5 or more
•Finish Landrace and Romanov –4 or more ovulations
•Assaf ewes by introgression the FecB (Booroola) gene
(Gootwine et al., 2001).
•NUTRITION
–Ad Libitum Feeding
•Swine –14 days prior to estrus increases ovulation rate
about 30%
•Sheep –Improved pasture or feed prior to onset of
breeding season

22. OVULATION RATE (continued)
•GENETIC SELECTION
–Nebraska Swine Herd
•Ovulation rates increased by 5 in eight generations and 7
ovulations in 10 generations
–France –Hyperprolific Large White –23 ovulations
vs 17 for control line
•NUTRITION
–Ad Libitum Feeding
•Swine –14 days prior to estrus increases ovulation rate
about 30%
•Sheep –Improved pasture or feed prior to onset of
breeding season

23. Fertilization Rate
•Swine –95% -Breed at 12 and 24 h after onset
of estrus
•Sheep –85-95% -Breed at 12 and 24 h after
onset of estrus
•Cattle –80-90% -Breed 12 h after onset of
estrus
•Mare –70 to 95% -Breed every other day with
expectation of ovulation 48h before end of
estrus or palpate to predict time of ovulation
and breed accordingly

24. Breeding Soundness for Males
•Quality of Semen
–Color –White to Cream colored –no blood etc
–Sperm Motility –Greater than 50% minimum
•Circular Movement
•Forward Motility Desirable
–Abnormal sperm
•Broken Tails
•Cytoplasmic Droplets
•Crooked Tails
•Abnormal Acrosome
–Sperm concentration
–Total sperm
•Summer Sterility

25. Minimum Age for Males for
Breeding
•Bulls –9 months
•Stallion –18 months
•Rams –8 months
•Boars –8 months
Breeding Soundness Evaluation Very
Important

26. Embryonic Death Losses
•Uterine Environment –Why don’t all embryos
die?
•Early Embryonic Deaths Predominate
–Oocyte
•Meiotic Maturity
•chromosome Abnormalities
–Nutrition –Overnutrition increases embryo deaths
–Environment
•Heat Stress
•Toxicant
–Endocrine Deficiencies

27. Embryonic Death Losses
•Oocyte Quality (Nebraska Study, Koenig)
•Meiotic Maturity
•Chromosomal Abnormalities
•Higher Ovulation Rates and greater frequencies of
abnormal oocytes
•Pubertal vs Mature Females
•Embryonic Lethals
–Women (Boue 1975) –10,000 women in France
•90% of women abort before 14 days of pregnancy
•1500 spontaneous abortions
•62% abnormal karyotype
–15% monosomy
–72% triploidy
–6% tetraploidy
–7% -Other?

28. Nebraska Study -Swine
High Ovulation
Rate
Control Superovulated
18.4 CL 15.0 CL 20.2 CL
68 % Ova
Recovered
81% Ova
Recovered
68% Ova
Recovered
14% Meiotically
Immature (MI)
9% MI 16% MI
27%
Chromosomally
Abnormal
(CA)(41.5% total
abnormal)
24% CA (32.5%
total abnormal)
27% CA (43%
total abnormal

29. Western U.S. A. Ewes
•USDA Idaho
1CL –90 lambs / 100 ewes
2 CL –175 lambs / 100 ewes
3 CL –190 lambs / 100 ewes

30. High Environmental Temperature
•Increase Ovarian and Uterine
Temperature
•Decrease Uterine Blood Flow
•Increase in Heat Shock Proteins
•Direct vs Indirect Effects
–Effect from onset of estrus to ovulation
–Oocyte maturation?
–Transriptional or translational events?

31. Abnormal Uterine Environment
•Environmental Estrogens
–Aflotoxins from moldy corn –swine become
pseudopregnant due to loss of embryonic
deaths around Day 15 of pregnancy –loss of
extracellular matrix of uterus
•Postpartum Period
–Inadequate uterine involution

32. French Large White, French Hyperprolific Large White
and Chinese Meishan Reproductive Performance
Breed Ovulation
Rate
Litter SizeEmbryo
Mortality
French,LW
Control
18 12 26 +7
FLW
Hyper-
prolific
23 13 41 +7
Meishan 17 16 16 +9

33. Time of Embryonic Loss
•Pig –Days 9 to 12 (70%); 12 –18 (25%)
and 18 to term (5%)
•Sheep –Days 8-14 (70%)
•Cows –By Day 17 (85%)
•Mare –By Day 14-15 (85 to 90%)

34. Porcine Placentation

35. Peri-Implantation Events

36. Days after mating
Embryo
migration
Fimbria
Oviduct Utero-tubal
junction
Implantation
Progesterone
Estradiol
150µ 170µ 205µ 340µ
190 mm30
mm
425µ
840
5
10
1612 20
3
6
Conceptus
position
Conceptus
Development
Estradiol
(pg/ml)
Progesterone
(
ng
/ml)
oIFNproduction
by trophoblast
Shedding of
zona pellucida
Peri-Implantation Events

37. Uterine Capacity
•Biochemical and Physiological Limitations to
Establishment and Maintenance of Fetal-Placental
Development to Term
–Endometrial Surface Area
–Uterine Secretory Activity
–Uterine Vasculature
•Low Resistance
•High Flow
•Capillary Bed Density
•Placentomes
•General Considerations
–Size
–Function
–Accommodation

38. Pig Placental Areolae
Day 70
•Number areolae correlated with
fetal growth and birthweight
-Knight et al.
(J. Anim. Sci. 1977; 44:620)
-van Rens & van der Lende.
(Theriogenology 2002;
57:1651)

40. Western Range Ewes in USA
CL Lambs/100
Ewes
Advantage
(%)
1 97
2 170 +73%
3 192 +18%

41. Age and Frequency of Twins in
Holstein and Beef Cows
•Heifers –1.3%
•4 years of age –4.4%
•10 yeaers of age –7.1%
•Beef Cows –0.2 to 0.6%

42. Pregnancy Following Ipsilateral vs Bilateral
Embryo Transfer in Beef Cows
Day of
Pregnancy
Ipsilateral
Transfer: 2
Blastocysts
Contralater
al Transfer:
2
Blastocysts
Bilateral
Transfer: 2
blastocysts
30 11/15 5/15 10/15
110 10/15 2/15 4/15

43. Intrauterine Migration of
Blastocysts
•Sheep –Yes, when there are multiple
ovulations
•Cattle –Rare, less than 10% regardless of site
of ovulation
–Sreenan and Beehan (1976) indicated 75% to 81%
embryo survival in 52 dairy heifers following
bilateral embryo transfer

44. Problems with Multiple Offspring in
Cattle
•Freemartins
•Abortions at about 150 to 180 days
•Small calves with high mortality
•Cows abandon one calf
•Retained placenta from 6 –11% for cows with
single calf to 66% to 100% in cows giving birth
to multiple calves

45. Characteristics of Prolific Breeds of
Sheep and Pigs
•Moderate increase or no increase in ovulation
rate
•Increased embryonic survival
•Smaller, but uniform placentae
•Smaller, but uniform birth weights of offspring
•Increase in mammary development –milk
production or increase in number of glands
•Increase in uterine vascularity
•Models for functional genomic inquiries

46. COW