Reproductive Aging Flashcards
Describe the development of the Medial Basal Hypothalamic LHRH Neurons (Pulse generator) from Fetus to Puberty.
Fetus: Active by 80 days gestation
Early Infancy: Highly functional at 12 days old
Late infancy/Childhood: Pulse generator inhibited by Intrinsic CNS (maximized by 4yo)
Late Prepubertal: Effectiveness of Intrinsic CNS inhibition decreases
Puberty: Further decrease in inhibition of Pulse Generator
Describe the development of the Gonadal Steroid Negative Feedback mechanism
Fetus: Maturation of the negative gonadal steroid feedback mech by 150 days gestation
Late Infancy/Childhood: Negative feedback control of FSH/LH secretion highly sensitive to Gonadal Steroids (low set point)
Late Prepubertal: Hypothalamic-pituitary unit Sensitivity to Gonadal Steroids decreases
Puberty: Further decrease in sensitivity of negative feedback mech to gonadal steroids
Describe the change in LHRH secretion from Fetus to Puberty
Fetus: Unrestrained secretion from 100-150 days gestation; low secretion at term.
Childhood: LHRH Pulse gen. inhibited by Intrinsic CNS; low amp/freq of LHRH discharges
Late prepubertal: Increased Amp & Freq of LHRH pulse (prominent with sleep)
Puberty: Increase in episodic secretion and gradual shift to adult pattern (approx every 90 min)
Describe how FSH & LH secretion changes from Fetus to Puberty
Fetus: Pulsatile secretion of FSH & LH by 80 days gestation
E. Infancy: Prominent FSH & LH episodic discharges until 6 months (male) or 12 months (female) with transient increases in plasma test (males) and estradiol (females)
L. Infancy: Low secretion of FSH & LH
L. Prepubertal: Increased Secretion
Puberty: Pulsatile secretion of LH follows pattern of LHRH pulses
What are the (3) stages of reproductive aging?
How does FSH levels change between them?
Reproduction: Normal/ Elevated FSH
Menopausal Transition: Elevated FSH
Postmenopause: Elevated FSH
What is Premature Ovarian Failure?
POF occurs when a womens ovaries stop working normally prior to 40.
Results in infertility and irregulary Estrogen/Progesterone production.
This differs from Premature Menopause (periods stop prior to 40)
What are potential causes of Premature Ovarian Failure/ Insufficiency?
- Follicle Related;
- Working Follicles run out early
- Follicles are not working properly
- Low number of follicles
- Intrinsic:
- Autoimmune Diseases (Thyroiditis and Addision Disease)
- Metabolic Disorders
- Extrinsic:
- Toxins Cigarete smoke, chemicals, pesticides
- Chemotherapy or radiation therapy
Estrogen decline is associated with what effects?
Of Interest;
Bone mineral Mass Fractures
Coronary Heart disease
Atherosclerosis
Describe the layers of the Endometrium.
What layer lies below the Endometrium?
- Endometrium
- Functional Layer
- Basal Layer
- Myometrium
Describe the effects of the LH Surge on the Ovary/Follicle (5)
- Stimulates completion of the 1stmeiotic division of the oocyte (via 2o messenger from Granulosa)
- Increase in Antrum size & Blood flow to the follicle
- Granulosa Cells: Secrete Progesterone & Decrease Estrogen
- Degradation of Follicular-Ovarian Membrane: Allowing oocyte & granulosa cells to move to the surface of the ovary
- Transform granulosa & theca cells to Corpus Luteum (which produces progesterone & estrogen)
Following Ovulation, how does the elevated Progesterone levels affect body temperature?
Increased Progesterone cause a rise in body temperature
This is modulated by E2 levels. Thus if E2 is low, then lower the effect.
Describe the effects of the LH Surge on the Graafian Follicle (~1.5cm)
LH Surge → COX2 Expression
COX2 induce Granulosa cells to produce Tissue Plasminogen Activator (tPA) into the Follicular Fluid
tPA activates Plasminogen, which subsequently is cleavage and activated to Plasmin
Plasmin activates Metalloproteases (MMP’s)
MMP’s induce perifollicular degradation
What are the cumulus cells that surround the Oocyte?
What do they produce/release?
Corona Radiata: Specialized Granulosa cells that secrete Progesterone
What is the significance of the Progesterone that the Cumulus cells (Corona Radiata) secrete?
Progesterone modulates the activity of CatSper (Sperm specific pH-sensitive Ca2+ channel)
Sperm essentially uses progesterone as a homing signal to swim toward the oocyte.
(Along with pH gradient; slightly alkaline mucus plug of cervix)
Briefly/generally describe the process of Capacitation.
- Non-Capacitated sperm are slow-paced and express certain surface glycoproteins
- They Bind to oviductal epithelium, causing a change in surface glycoproteins and a decrease in intracellular calcium
- decreased calcium causes an increase in intracellular ATP
- Capacitated Sperm become Hyperactive and initiate Tyrosine Phosphorylation
Approximately how long is the journey for a spermatazoa to the Ampulla of the Fallopian Tube?
5-10 Min; ~1.8 cm/min or 0.0007 mph
Describe the Steps of Fertilization
- Sperm maneuvers through the cumulus cells (Corona Radiata; Granulosa cells) and binds to zona pellucida
- Binding triggers an increase in sperm [Ca2+]i which then triggers the Acrosomal Reaction (exocytosis of the acrosome)
- Hydrolytic enzymes degrade the zona pellucida (cumulative action)
- (eventually) the sperm and oocyte membranes fuse, causing a rise in oocyte [Ca2+]i, then triggering the Cortical Reaction
- Exocytosis of Cortical granules cause the Zona Pellucida to harden (preventing Polyspermy)
- Rise in oocyte [Ca2+]i also induces completion of the Second Meiotic Division and formation of the second polar body
- Head of the sperm enlarges & becomes the male pronucleus (N)
- Male & female pronuclei fuse (time=0)
Describe a brief summary of Fertilization events
- Sperm binds to Zona Pellucida, inducing the Acrosomal Reaction
- Sperm enters egg causing rapid depolarization of the egg
- Influx of calcium induces the Cortical reaction; hardening of Zona Pellucida
- Influx of Calcium induces completion of Second Meiotic Division
- Metaphas of First Cleavage division
Describe the events occuring from Fertilization up to Implantation
- Zygote begins to move towards the uterus
- Cleavage; Mitotic divisions resulting in daughter blastomeres without an increase in overall size of zygote (2-cell stage ~30 hours)
- Morula (~72 hours) enters the uterus
- Compaction: differentiation/organization of blastomeres into (2) cell groups (Embryoblast & trophoblast) and a Blastocyst cavity. (Embryo is polarized)
- Hatching: Blastocyst hatches from the Zona Pellucida (by day 5) allowing direct association to the endometrial lining
- Implantation: Embryonic pole associates with the endometrial lining and triggers the Decidual Reaction
What is the most common site of implantation?
What is an abnormal site of implantation?
The Posterior Uterine wall is the most common site of implantation.
Ectopic Pregancies are those in which implantation occurs outside uterus/endometrial lining. (i.e. oviduct)
Describe what Placenta Previa is.
Placenta Previa occurs when the Blastocyst implants too close to the opening of the cervix and results in the placenta partially (or fully) covering the cervix.
Once the trophoblast associates with the endometrial lining, what occurs?
The trophoblast is induced to proliferate and differentiate rapidly and invade the endometrium which further imbeds it into the endometrium. This continues until completely embedded.
This gives rise to a stratified multi-layered mass of (2) cell types;
- Syncytiotrophoblast
- Cytotrophoblast
What is significant about syncytiotrophoblast cells?
Extremely invasive cell line that secretes human Chorionic Gonadotropin (hCG) (which prevents corpus luteum degradation)
How does the Amniotic Cavity develop?
Day 8: (following Bilaminar Germ disc formation)
Forms due to fluid accumulation in the Epiblast
Explain the development of the Chorionic Cavity
Day 12-15:
The Chorionic Cavity (aka ExtraEmbryonic Coelom) forms in the ExtraEmbryonic Mesoderm layer, splitting the layer with the exception of the connecting stalk.
Identify the major structures present on;
A. Day 8
B. Days 12-15
C. Day 20
A. Amniotic Cavity & Embryonic (bilaminar) Disc
B. Chorionic Cavity (forming)
C. Gastrulation (trilaminar germ disc) & Tertiary stem Villi
What does the Endoderm give rise to?
- Lining of the gut
- Gut Derivatives;
- Liver
- Pancreas
- Lungs
What does the Mesoderm give rise to?
- CV system
- Connective tissues
- Blood
- Bone
- Muscle
- *Epithelial layers of the Respiratory System
What does the Ectoderm give rise to?
- Epidermis;
- Hair
- Nails
- CNS
Secretion of what signaling molecule begins on day 8?
What does this signaling molecule cause on day 10?
Day 8: Syncytiotrophoblast secretion of hCG
Day 10: hCG “Rescue” of Corpus Luteum
Identify the (3) prenatal stages from conception to birth.
How long does each approximately last?
- Germinal Period:
- First 2 weeks
- Germinal layer development
- Embryonic Period:
- Week 3 to 8
- Organ system Development
- Fetal Period
- Remaining 30 weeks
- Organ system Growth & maturation
When/how is the beginning of pregnancy determined?
Clinical estimation of pregnancy is counted from the last menstrual period (~2 weeks prior to fertilization)
Identify the Trimester time-frames and estimated delivery date.
1st Trimester:
-(12 Weeks/3 months); Weeks 0-12
2nd Trimester:
-(12 Weeks/3 months); Weeks 13-24
3rd Trimester:
-(12 Weeks/3 months); Weeks 25-36
Estimated delivery date:
- 40 weeks from start of pregnancy
- 38 weeks from fertilization
What is the viability of a birth occuring at week 24 (pregnancy)?
50%*
(Verify this slide)
At the end of which week marks the end of the critical period for MOST of the Organ Systems?
Which organ systems are still developing at this point?
End of Week 10
The Gut, Palate, & External Genitalia are still in critical periods at this point.
Teratogens introduced within the first 10 weeks may result in what type of abnormalities?
Following the first 10 weeks?
First 10: Major morphological abnormalities (potential for miscarriage)
Following: Functional Defects & Minor morphological defects
What is the leading cause of fetal death?
Alcohol
Air pollution during the first (2) weeks can result in
Loss of conceptus (miscarriage)
