Fertilisation Flashcards
How does the tail of the epididymis facilitate sperm maturation?
- Fluid absorption leads to a higher concentration of sperm.
- Epididymal cells secrete substances including fructose, proteins, and glycoproteins, facilitating sperm maturation.
- Secretions also contribute to the composition of seminiferous fluid, providing sperm protection.
What are the key changes the sperm undergo in the male tract?
- The acrosome, filled with hydrolytic enzymes, is bound by membranes that will later be involved in the acrosome reaction.
- Sperm plasma membrane becomes more fluid due to protein transfer, which is crucial for future acrosomal binding.
Flagellar changes begin in the epididymis:
- The tail becomes more rigid, allowing stronger and more effective propulsion
- Driven by an increase in cyclic AMP (cAMP) content within the tail.
What features of the female reproductive tract enable sperm capacitation?
Proteolytic enzymes
Cholesterol depletion
Higher ionic strength
*sperm NEED capacitation to be able to fertilise
What are the key changes to the sperm during capacitation?
- Hyperactivation of the flagellum
- Membrane modifications preparing for the acrosome reaction
What are the capacitation mechanisms?
- Enhancing sperm responsiveness to oocyte signals, increasing the likelihood of successful fertilisation.
- Surface glycoprotein modifications occur on the sperm plasma membrane.
- Cholesterol reduction and lipid raft depletion reduce membrane stability, increasing fluidity.
- Facilitates fusion of the sperm plasma membrane with the acrosomal membrane, allowing acrosomal contents to be released. (acrosome reaction)
What is the biological pathway of capacitation?
- Intracellular alkalinisation occurs, raising sperm cytoplasmic pH.
- Elevated pH increases calcium permeability, raising intracellular calcium concentration.
- cAMP levels increase due to enhanced adenylate cyclase activity, activating protein kinase A (PKA).
- PKA activation leads to phosphorylation of key proteins, triggering further downstream signalling events.
- These biochemical changes drive modifications in both the sperm membrane and flagellum.
What is meant by hyperactivated sperm motility?
- Hyperactivated sperm exhibit high-amplitude, asymmetric flagellar beating
- Pathway analysis reveals that hyperactivated sperm move in an erratic, non-linear fashion compared to control
What are the functional benefits of hyperactivated sperm motility?
- Detachment from surfaces where the sperm may become trapped.
- Navigating the oocyte through irregular motility patterns.
- Penetrating the cumulus oophorus and subsequently the zona pellucida.
What is the role of CatSper in hyperactivation?
- CatSper is a sperm-specific, calcium-gated ion channel that is activated by an alkaline pH.
- Essential for hyperactivation and fertility.
- KO of CatSper impairs these processes, leading to infertility.
- Sperm lacking functional CatSper channels exhibit reduced movement amplitude compared to normal sperm.
What is the journey of the sperm to the egg?
- Oocyte released from the ovary and remains in the upper oviduct.
- Sperm must travel through the cervix, uterus, and uterotubal junction to reach the CORRECT oviduct.
- Fertilisation occurs in the upper oviduct, but can also take place lower in the tract if the oocyte begins its descent.
What is sperm migration guided by?
- Oocyte-released chemoattractants.
- Ciliary beating in the oviduct aiding movement.
- Some sperm are trapped and degraded by ciliated epithelial cells via phagocytosis.
Give some challenges the sperm have to face reaching the egg
- Cervical mucus and folds blocks most sperm, except during ovulation when mucus thins.
- Immune cells attack sperm as foreign bodies.
- Uterine contractions can push sperm forward or back.
- Fluid turbulence and currents washes away weaker sperm/help others
-Vaginal acidity (pH ~3.5-4.5) is highly toxic to sperm. - Incorrect oviduct selection leads sperm to the wrong tube.
- Hyperactivation is needed to break free from obstacles.
What % of sperm do not reach the cervix?
99%
How long do the sperm/oocyte last for?
- The oocyte remains viable for 6-24 hours post-ovulation.
- Sperm can survive 24-48 hours in the female reproductive tract.
What happens when the sperm reaches the zona pellucida?
- Hyperactivated sperm burrow through cumulus cells.
- The acrosome reaction releases hydrolytic enzymes.
- Acrosome reacts with the perivitelline space.
What happens when the sperm and egg plasma membranes fuse?
- Sperm nucleus enters the oocyte.
- Midpiece and tail remain outside.
What are the four glycoproteins of the zona pellucida?
ZP1 – Structural protein, crosslinks others.
ZP2 – Important for secondary sperm binding and polyspermy block.
ZP3 – Facilitates primary sperm binding.
ZP4 – Complexes with ZP3 for species-specific binding.
How are zona pellucida glycoproteins named?
Named in order of discovery, not in functional order.
What triggers the acrosome reaction?
- Sperm binding to ZP3/ZP4 on the zona pellucida.
- Considered the terminal phase of capacitation.
What happens during the acrosome reaction?
- Acrosome swells and fuses with sperm plasma membrane.
- Exocytosis releases acrosin (on the inner sperm membrane) and hyaluronidase to digest the zona pellucida.
What are the key steps of gamete binding?
- Primary Binding – Sperm binds ZP3/ZP4 via a species-specific receptor.
- Acrosome Reaction – Acrosin is exposed for deeper penetration.
- Secondary Binding – Inner acrosomal membrane binds ZP2.
- Equatorial Region Adhesion – Sperm binds oocyte plasma membrane.
- Sperm Entry – Sperm head enters oocyte, releasing the nucleus.
What enzyme triggers oocyte activation?
Sperm-derived PLCζ.
How does PLCζ activate the oocyte?
- Triggers second messenger cascades.
- PIP2 is cleaved into DAG and IP3, activating PKC.
- Ca²⁺-induced Ca²⁺ release causes calcium oscillations.
- Resumes final meiotic division which had previously been arrested
What is the cortical reaction?
- Cortical granules release ovastacin into the perivitelline space.
- Important for the block to polyspermy.
How does the zona pellucida prevent polyspermy?
- Zona pellucida hardens at the sperm entry point.
- Ovastacin cleaves ZP2, preventing further sperm binding.
What happens after sperm binding to the oocyte?
- Male and female pronuclei form.
- Female pronucleus forms via extrusion of the second polar body
- They migrate to the center of the zygote.
- Syngamy occurs – nuclear membranes break down, chromosomes align.
What happens in early embryo development?
- First cleavage produces two identical cells.
- Divisions remain symmetrical, forming a morula.
- Blastocyst forms inside the zona pellucida.
What happens when the blastocyst hatches?
It exits the zona pellucida and implants in the uterus within one week.
What hormones maintain pregnancy?
- Corpus luteum produces progesterone.
- Placenta takes over hormone production later.
- Oestrogen and progesterone suppress ovulation.
- hCG (human chorionic gonadotropin) is secreted by the placenta and detected in pregnancy tests.
