Lecture 22 Flashcards
When does pregnancy begin and how long does it last according to textbooks and legal rulings?
When the fertilized egg has implanted in the wall of the uterus; about 38 weeks/266 days
When does pregnancy begin and how long does it last according to clinical practice?
Day of the last menstrual period; about 40 weeks or 280 days
When is the conceptus called a preimplantation embryo (pre-embryo?)
Until about 7 days after fertilization
What is the term for the conceptus from weeks 3 to 8?
Embryo
At what point in time is the conceptus called a fetus?
After week 8
What are positive signs of pregnancy?
- Detection of a fetal heartbeat
- Feeling the fetus moving
- Visualization of the fetus by ultrasound
- Positive hCG preganncy test
What are presumptive signs of pregnancy?
- Missed menstrual period associated with coitus during the previous month
- Nausea after awakening (morning sickness caused by change in stomach function at this time)
- Increase in size and tenderness of the breasts and darkening of the areola
What are probable signs of pregnancy?
- Indicators that in all likelihood, a woman is pregnant
- Increase in size of the abdomen and increased frequency of urination (because uterus presses on urinary bladder)
- Uterine cervix becomes softer by the sixth week of pregnancy (Hegar’s sign)
What is “The Rabbit Died”?
A euphemism for positive pregnancy tests due to the fact that pregnant women’s urine would kill rabbits
Other than determining positive pregnancy, what other time is hCG noticeable in blood?
With certain hCG secreting cancers called choriocarcinomas.
What was the first pregnancy test called?
e.p.t, “early pregnancy test” and later called “error proof test”
When is hCG produced in pregnancy?
It is produced by the placenta shortly after pregnancy was established.
How is pregnancy tested now?
The current method uses a monoclonal antiobody for hCG (anti-hCG) in an at-home ELISA/lateral flow detection test.
When can hCG be detected in blood?
About 11 days after conception
When can hCG be detected in urine?
About 12-14 days after conception
When can pregnancy tests first detect pregnancy?
About 12-14 days after conception, when the hCG is detectable in urine.
How often do hCG levels double?
Every 72 hours
When are the peak levels of hCG?
First 8-11 weeks of pregnancy
What concentration of hCG proves nonpregnant vs. pregnant?
< 5 mlU/ml vs > 25 mlU/ml
How is hCG a part of maternal recognition of pregnancy?
- Pregnancy tests
- Sends signal to brain
How does hCG behave?
As an agonist of LH, stimulating progesterone secretion by the corpus luteum to maintain structure and function. Also has a role in the quiescence (inactivity/dormancy) of the myometrium and local immune tolerance.
What are the subunits of hCG?
- Alpha subuinit (identical to pituitary gonadotropin hormones) contains two N-glycosylation sites and is encoded by a single gene (CGA0
- Beta subunits are distinct in hCG and varies in its glycosylation state with the stage of pregnancy, its source of production and in the pathology
What is hCG mainly secreted by?
Syncytiotrophoblast
What are the structures that produce hyperglycosylated hCG-H?
- Invasive extravillous trophoblast
- Choriocarcinomas
- Pituitary gland
What are the autocrine and paracrine roles of hCG?
- Formation of the syncytiotrophoblast and angiogenesis thorugh LHCG receptor
- hCG-H stimulates trophoblast invasion and angiogenesis by interacting with the TGF beta receptor 2
What broader influence on fetal and maternal pathways for the purpose of allowing proper implantation and placentatin does hCG hold?
- Fusion of cytotrophoblast cells into multinuclear structure of the syncytiotrophoblast
- Formation of the umbilical circulation in villous tissue
- Formation of the umbilical cord
- Growth of fetal organs
- Angiogenesis by through development and growth of uterine spiral arteries uSA
- Suppression of myometrial contractions
What molecules does hCG target?
- Prolactin
- Insulin-like growth factor binding protein-1
- Macrophage colony stimulting factor
- Leukemia inhibitory factor (LIF)
- Vascular endothelial growth factor (VEGF)
- Matrix metalloproteinase (MMP)-9
- Tissue inhibitors of MMPs (TIMPs)
- Galectin-3
- Glycodelin
What do all of hCG’s target molecules have in common?
They are all involved in decidualization, implantation, vascularization and tissue remodeling
What is luteolysis?
In mares, PGF is metabolized a lot less than in other species, and they are more sensitive to it,which is why there is less uterine-ovarian vascular connection in mares
What cells have PGF2a receptors?
Large luteal cells
Do small luteal cells have PGF2a receptors?
No, as theca does not contribute significantly to SLC and is instead derived from other cell types following ovulation.
What is an embryo capsule?
- A casule that protects the conceptus during its extensive migration until Day 16 in mares
- Keeps the embryo spherical
- Stores and exchanges conceptus proteins
- Protects the conceptus from the maternal immune system
What is the timeline of an equine embryo capsule?
- Day 5 (after ovulation): acellular glycoprotein membrane forms between zona pellucida and trophectoderm after the entry of the embryo into the uterus
- Day 7.5: blastocyst hatches, composed of mucin-like glycoproteins that are produced by the trophoblast and modified by the uterine environment to produce mechanical strength and resistance to chemical or enzymatic solubilization
- Day 21: equine capsule no longer persists and the physical barrier between the trophoblast and uterine epithelium is gone
What is the point of embryonic migration in mares?
The conceptus spends 5 to 20 minutes at each location to distribute pregnancy factors over a wide surface of the endometrium
What is the process to create embryonic mobility?
- Embryo stimulates uterine contractions for mobility
- Mobile embryo blocks uterine-induced luteolysis
- Mobile embryo distributes substances to increase uterine tone and decrease uterine diameter
- By the time blockage of luteolysis is completed, uterine diameter has decreased and embryo has increased so that fixation occurs at the flxure in a caudal horn
How is eCG released?
By endometrial cups
What is the purpose of eCG?
Induction of the secondary corpus luteum, which is after maternal recognition of pregnancy
When does the eCG first appear?
Day 40, which is the last day the secondary corpus luteum can be formed
How many CL are formed at 70 and 140 days?
2.4 and 10.2 on average
What happens between day 40 and 70?
Ovulatory CL persists
What happens after 70 days?
Anovulatory follicles are luteinized
What make up endometrial cups?
Allantochorionic girdle cells that are localized distinct from diffuse microcotyledonary placental attachment
What activity does eCG produce in mares and how does that differ in other animals?
- Mares: only LH activity
- Everything else: LH and FSH activity
How is pregnancy established in a sow?
- Embryos migrate between horns from day 8 to 12 and there must be
a minimum of 2 embryos in both horns before day 12.
What happens to the conceptuses throughout the uterin horns?
They elongate.
What is the role of IL1B2 in elogation of porcine conceptuses and how was it discovered?
Elongation occured on day 14 in wild type (IL1B2 +/+) conceptuses, but not in null conceptuses, which was found via CRISPR/Cas9.
What other cytokine could be involved with recognition of pregnancy in swine?
IFNG
What role do estrogens perform in swine?
They are luteotrophic and not responsible for maternal recognition
What tissue in swine is responsive to estrogens?
The endometrium.
When is estrogen necessary in pregnancy in swine?
Beyond 24 days, it is not essential before that
What enzyme was used to reveal the lack of need of estrogen for early maintenance?
CP19A1 (aromatase)
How is luteolysis controlled in ruminants?
- Progesterone fails to inhibit production of uterine PGF2a
- Endometrial PGF2a enters uterine vein
- PGF2a moves into ovarian artery through counter-current exchange
- PGF2a delivered to ovary and regresses CL
- Pregnancy must block luteolysis (action of PGF) on corpus luteum
What is the process of functional luteolysis?
- P4 blocks synthesis of estrogen receptor (ESR) and oxytocin receptor (OXTR)
- Prolonged exposure to P4 results in a loss of ability of P4 to inhibit ESR and OXTR
- Low amounts of estradiol bind ERS and induce OXTR
- Low amounts of oxytocin from ovary bind OXTR and induce prostaglandin F2-alpha (PGF)
- PGF induces an increase in oxytocin (positive feedback loop)
- PGF causes functional and structural regression of the corpus luteum (luteolysis).
How does maternal recognition work in ruminants?
- No conceptus: PGF pulses cause regression of CL
- Conceptus Present: PGF pulses are attenuated and CL is rescued, pattern of PGF pulses changes
When does MRP occur in cattle?
By day 14
How did scientists discover when MRP ocurs?
- Embryo transfer prior to day 14: surviving conceptuses
- Embryo transfer after day 14: embryos died and cattle cycled again
What was confirmed to signal maternal recognition of pregnancy?
IFNT
How does the hatching from zona pellucida in bovine work?
It is facilitated by plasmin which is produced from plasminogen.
What happens to the embryo of cattle on day 9-11 in terms of shape?
Spherical to tubular shape
What are the endocrine actions of pregnancy/IFNT?
- Induce genes in endometrium, blood cells and CL
- ISGs in the CL temporally follow induction in the endometrium and release of IFNT from the conceptus
- Uterine vein blood from pregnant ewes has antivral activity
- Pre-adsorption (particles sticking to a surface) with anti-IFNT antibody blocks antiviral activity in uterine vein blood from pregnant ewes
- IFNT is detected in uterine vein blood from pregnant ewes using RIA and MS
- 0.3-3 pg/ml IFNT induces ISGs in cultured large, small and mixed luteal cells
- Systemic infusion with IFNT for 12-24 hours protects the CL from lytic action of injected/exogenous PGF2a in ewes
What are binucleate giant cells?
Cells that migrate from the chorion to the endometrial epithelium in ruminants. These cells are thought to secrete placental lactogen and pregnancy specific protein B
How does MRP work in rodents?
- Not through the action of hormones from other species
- During pseudopregnancy, initiated by mating to a sterile male or by scratching/stimulating the cervix of a receptive female, the cycle is lengthed to 12 days before luteal regression.
- Surges of pituitary prolactin release caused by stimulation of the pelvic nerve and activation of a neural reflex arc during mating causes extension of CL life span
- Prolactin maintains luteal cell LH receptors and may provide luteal resistance against PGF2
- After establishment, several placental lactogens and prolactin-like hormoens produced by the placenta and deciduum replace pituitary prolactin at about mid-gestation
