fertilisation and contraception Flashcards
(18 cards)
sperm maturation starts in the epididymis - what does this involve?
This is stimulated by androgens (leydig - testosterone, sertoli convert this etc…)
Fluid used to wash sperm through tubules is absorbed even more to make the semen 100x more concentrated
Cells in the epididymis secrete fructose, proteins and glycoproteins that help drive maturation and contribute to the protective seminal fluid
what ‘maturation changes do sperm undergo in the male tract?
Membrane changes - to both the plasma membrane and just below that the acrosomal membrane, increase fluidity of PM, and transfer proteins that are essential for future acrosomal reaction.
Nuclear condensation: Disulfide cross-linking stabilizes DNA.
Capacitation suppression: Factors like CRISP-1 maintain sperm in a non-reactive state until ejaculation
Flagellum changes - structural protein alterations such as more cross links between outer dense fibres make the tail more rigid so it can beat stronger
what triggers capacitation in the female tract?
what are the two main changes?
proteolytic enzymes, cholesterol sinks and greater ionic concentrations of the female tract
1) hyperactivated motility
2) changes in membrane properties that will allow the acrosome reaction to happen
more specifically, what sort of cascade i suppose, occurs in capacitation starting with a rise in pH and what does it achieve?
Sperm cytoplasm becomes more alkaline
This higher pH increases calcium permeability (by activating Cation channel of sperm, CatSper) and so intracellular calcium concentration rises
As a result → inc adenylate cyclase activity and cAMP production
Activation of spermatozoal protein kinase A (PKA)
Leads to downstream phosphorylation of e.g. flagellum proteins; also triggers other signalling pathways contributing to membrane remodelling and priming for acrosome reaction
what exactly is hypermotility?
Basically is when you’ve got fast, high amplitude, asymmetric beating of the flagellum, to help sperm meet target and penetrate through cumulus cells and zona pellucida.
Have even observed “star spin” like behaviour, thought to be useful in navigating cilia that can trap sperm
give an overview of fertilisation process
Sperm in vaginal tract.
>99% of sperm do not pass through the cervix — highlighting the need for high sperm count.
A small fraction of sperm enter the cervix and move through the uterus toward the oviducts (fallopian tubes).
Movement is aided by:
Flagellar motility of sperm
Cilia lining the female tract
Uterine and oviductal contractions
sperm distributed approximately equally between both oviducts.
Only sperm in the oviduct containing the ovulated oocyte (usually the ampulla) have a chance at fertilisation.
The oocyte and surrounding cumulus cells release chemoattractants, these guide sperm toward the oocyte via chemotaxis.
Reaching the Oocyte
The oocyte is surrounded by a layer of cumulus cells embedded in a hyaluronic acid matrix.
Sperm surface hyaluronidase helps digest the extracellular matrix, enabling sperm to reach the zona pellucida (a glycoprotein shell around the egg)
overview of sperm-egg interaction?
Hyperactivated sperm need to burrow through cumulus cells surrounding zona pellucida
After, acrosome reaction with the zona pellucida occurs but only if capacitation has previously taken place. Further binding reactions
Perivitelline space = between zona pellucida and egg plasma membrane.
Fusion of egg plasma membrane with sperm plasma membrane
Sperm nucleus taken up into oocyte (midpiece and tail remain outside)
Cortical granules present inside the egg are exocytosed, preventing multiple sperm binding by e.g. cleaving ZP2
explain the acrosome reaction + how sperm interact with zona pellucida (including the functions of its ZPs)
Zona pellucida has four key glycoproteins important in sperm-binding
ZP1 = structural protein that cross-links the other ZPs
ZP3 is complexed with ZP4 and is what the sperm binds to first (primary binding). Note that the binding partner on the sperm here is species-specific, and that removal of certain proteins can allow for cross species fertilisation
The Z-proteins are responsible for inducing the acrosome reaction…
upon binding to ZP3/ZP4 complex, Sperm acrosome swells; the acrosome membrane fuses with the sperm plasma membrane. Acrosomal vesicle undergoes exocytosis, Acrosin and hyaluronidase digest zona pellucida, entering perivitelline space
ZP2 is responsible for the secondary binding - where the sperm INNER acrosomal membrane binds to ZP2 via its own ‘acrosin’ protein (can’t anchor or penetrate properly without ZP2)
Adhesion of sperm equatorial region to the oocyte membrane
Penetration of sperm head into oocyte
what protein is important for penetration of oocyte membrane?
Izumo1 on sperm (relocated after acrosome reaction to equatorial region) binds Juno on oocyte membrane, facilitating penetration
oocyte activation - upon sperm head entering the oocyte, what happens to trigger a what spike?
these spikes result in three key things?
PLC-zeta is released into oocyte cytoplasm… PIP2 cleaved at membrane to DAG and IP3, IP3 triggers Ca2+ release from intracellular calcium stores - causing a series of calcium SPIKES (up down up down)
- cause egg activation and resumption of MII (previously arrested at metaphase 2)
- Also triggers the release of cortical granules, including ovastacin, which along with Zn2+ cofactor, cleaves ZP2 to prevent further sperm binding and polyspermy. Also hardens the zona pellucida
- Calcium spikes also lead to activation of PKC, which phosphorylates other proteins essential for initiating development of the conceptus
what nuclear changes occur from oocyte activation leading to fusion of the genomes?
Sperm nuclear envelope breaks down, and chromatin decondenses, protamines replaced back with histones → forms the male pronucleus
Meanwhile, oocyte completes meiosis II (due to Ca2+ spikes ^)
Produces the second polar body, and forms the female pronucleus
Both pronuclei (male and female) migrate towards each other within the cytoplasm, guided by microtubules and sperm-derived centrosome, replicating their DNA as they approach one another
Syngamy (fusion of genomes) as nuclear envelopes break down and replicated chromosomes align on a shared mitotic spindle ready for first cleavage division
briefly explain the next part - early embryo development
After fertilization, the zygote undergoes a series of rapid, symmetrical mitotic divisions called cleavage
- Progresses through 1 → 2 → 4 → 8 cells, with daughter cells (blastomeres) of equal size
- No cell growth between divisions → cells get progressively smaller. Divisions initially occur in synchrony
Around the 8-cell stage, cleavage becomes asynchronous and blastomeres begin to show differences in position and potential
Morula stage (~16–32 cells):
Solid ball of smaller blastomeres
Begins compaction — outer cells flatten and form tight junctions, inner cells form the inner cell mass (ICM)
Formation of blastocyst:
Fluid begins to fill the center, forming the blastocoel (blastocyst cavity)
Inner cell mass → will form the embryo
Trophoblast (outer layer) → will form the placenta
All of this occurs within the intact zona pellucida, which, Holds the embryo together and prevents premature implantation
Zona hatching:
Blastocyst must ‘hatch’ out of the zona pellucida before implantation in the uterus can occur
in pregnancy and detection, how is HPG axis supressed?
when is the 40 week estimate taken from?
Increased oestrogen and progesterone override monthly cycle and suppress HPG axis. Human chorionic gonadotropin hormone (HCG) produced by placenta
taken from first day of last period (2 weeks) and then 38 weeks of actual development
how does the pill work?
involve a progestogen with or without an oestrogen; this mimics the natural negative feedback on pituitary in second half of cycle (luteal) to keep FSH and LH low and prevent recruitment of follicles
when was female hormonal birth control introduced?
give two stats saying women aren’t happy with options
Female birth control pill first available in 1960s
257 million Women who want to avoid pregnancy are not using safe, modern contraceptives
91% of surveyed women stated that no current contraceptive had all the features they thought were extremely important
using two statistics, convey that the need for new contraception isn’t taken seriously
just 2% of the revenue from contraceptive sales is reinvested into research and development
between 2015 and 2024, the public health grant received by councils has been reduced in real terms by £880mn. This has resulted in a reduction in councils’ ability to spend on STI testing, contraception and treatment
Women continue to endure harmful side effects from hormonal contraception because it works — and companies exploit this, investing little in safer alternatives. As long as women keep paying, their health remains a low priority
what is an IUD?
hormonal IUDs (a small device that is placed in the uterus, where it releases hormones)
how does the copper IUD work/why is it not good?
Copper IUD bad - causes thickening and chemical alterations to cervical mucus due to cytotoxic inflammatory response - limit sperm motility/survival.
inflammatory response in uterine wall cells = prostaglandin release = toxic environment for sperm and eggs
relying on an Inflammatory response is not good - in uterine wall and causes cell distress and damage - severe cramping/pain, heavy bleeding
