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