Fertilisation and luteal phase Flashcards
Why is ejaculated semen coagulated?
- Prevents loss
- later liquifies so that sperm can swim out of the seminal fluid through cervical mucus into the uterus.
What parts of the semen does the cervical mucus remove?
Seminal fluid, abnormal sperm and cellular debris
What happens when sperm passes through the cervix?
- cervical mucus is less viscous in the absence of progesterone allowing sperm to pass
- sperm inhabits cervical crypts which may form a reservoir
- some evidence of thermotaxis
- survive in female for around 24-48 hrs
How do sperm make their way to the egg?
- currents set up by uterine and tubal cilia
- chemo-attractants released from oocyte cumulus complex - thermotaxis
- sperm become hyperativated. Forceful tail beats with increased frequency and amplitude mediated by Ca2+ influx via CatSper channels
What is sperm capacitation?
- Biochemical rearrangement of the surface glycoprotein and changes in membrane composition
- partly achieved by removing the sperm from the seminal fluid
- uterine and tubal fluid may contain factors promoting it
- has to occur to allow acrosome reaction
What is the acrosome reaction?
- occurs in contact with the cells surrounding the egg
- acrosomal membrane on the sperm head fuses releasing enzymes
- these cut through the outer layers of cumulus surrounding the egg
- acrosin bound to the inner acrosomal membrane binds and digests the zona pellucida so that the sperm can enter
How does ovulation get triggered?
- Consistently high levels of oestrogen flips the negative feedback on the pituitary into positive feedback
- causes the LH surge - a huge release of LH
- This triggers and inflammation reaction, producing cytokines, VEGF etc
- Follicular fluid is exuded with the oocyte inside
- Basement membrane breaks and so blood pours into the middle
- oocyte cumulus complex is extruded out and caught by the fimbrae of uterine tube
- theca and granulosa become mixed
What happens in meiosis I of the oocyte?
- Ovulated eggs are released in meiosis I
- Converts the primary oocyte into a secondary oocyte plus the first polar body
- undergoes uneven cell division so that the oocyte keeps all of the cytoplasm and cellular machinery
What does the progesterone produced by the corpus luteum do?
- differentiation of the endometrium - glands start to secrete glucose, growth factors, adherence molecules, which all make the endometrium more receptive, easily implanted into and highly vascularised with a large blood supply
- as progesterone rises later in the luteal phase, it suppresses the cilia in uterine tubes, as the fertilised oocyte will have already passed
- makes the cervical mucous viscous again (criss-crossing glycoproteins) to prevent further sperm penetration
What does oestradiol do in the luteal phase vs follicular phase?
L = Helps to maintain the endometrium F = causes proliferation
What happens if there is no fertilisation?
- After 14 days, the CL dies and becomes a corpus albicans
- Progesterone levels drop, and without it, the endometrum cannot survive. The endometrium starts to produce PGs that constrict the blood vessels, causing the tissue to become hypoxic and necrotic
- The fall in CL-derived steroids causes an inter-cycle rise in FSH, causing break down and bleeding.
What happens if there is fertilisation?
- Human chorionic gonadotrophin (hCG) is released by the embryo
hCG binds to FSH receptor in CL, keeping it alive and producing progeterone, maintaining the endometrium - It inhibits FSH and LH and stops the menstrual cycle, allowing pregnancy
Name 5 things the menstrual cycle achieves
- selection of a single follicle and oocyte
- regular spontaneous ovulation - one good egg a month
- correct haploid number of chromosomes in the oocyte
- cyclical changes in the cervix and uterine tubes to enable egg transport and sperm access
- preparation of the endometrium of the uterus to receive the fertilised egg
- support of the implanting embryo and enometrium by the CL progesterone
- initiating a new cycle if fertilisation does not occur
What does the oocyte look like at ovulation?
- can see the first polar body but no second (undergone meiosis I)
- remnants of the granulosa cells that were surrounding the oocyte in the follicle
- on the inside of the granulosa cells there is the zona pellucida, a glycoprotein layer secreted by the egg around projections. Binds sperm at ZP3 receptors. At LH surge, projections are withdrawn
- Cumulus cells - protect the egg, secrete mucus, matrix projections into the plasma membrane
- corona radiata is the innermost layer
- inside of the oocyte membrane there are cortical granules which will release contents at the point of fertilisation, preventing polyspermy
How does the sperm bind to and penetrate the egg?
- identifies a sensory molecule, likely mediated by CatSper channels
- Ca rushes into the sperm hyper-activating them, increasing the frequency and amplitude of the tail beating
- move the granulosa cells out of the way
- receptor molecules on the head of the sperm bind to proteins on the ZP, such as ZP3
- when binding occurs, the acrosome reaction occurs and enzymes flood out, cutting through the ZP, and the sperm fuses with the plasma membrane
- it is taken up by phagocytosis and the tail and mitochondria are left behind or destroyed
- Phospholipase Z in the sperm membrane causes Ca release inside the egg when it meets it
- Wave of Ca2+ sweeps around the egg, causin a cortical granule reaction, releasing proteases, peroxides and hyaluronic acid hardening the oocyte coat, preventing polysermy
What does the cortical granule reaction achieve?
- PL Z in the sperm membrane causes a release of Ca in the egg when they meet.
- This causes a wave of Ca sweeping around the egg, causing the cortical granule reaction
- proteases sever anchors between ZP and the egg, getting rid of any other proteins that another sperm can bind to such as ZP3
- peroxides cross-link and make it harden and prevent polyspermy
- hyaluronic acid released into perivitelline space. Has a lot of sulphate groups that absorb water, causing it to swell up and move away from the ZP
What is syngamy?
The fusion of two gametes in reproduction
What are the steps in syngamy?
- oocyte has undergone meiosis I, so has 23 chromosomes, but 2 copies of eah arranged as sister chromatids
- the sperm binds to the ZP before penetrating it and dusing with the oocyte membrane - causes an increasing in Ca2+, triggering the completion of meiosis II, expelling the second polar body
- sperm’s nuclear membrane breaks down, the chromatin decondenses and chromosomes separate
- 4-7 hours later, the two sets of haploid chromosomes beome surrounded by distinct membrane forming pronuclei
- inside the pronuclei, both sets of haploid chromosomes get duplicated
- pronuclear membranes break down and the mitotic metaphase spindles forms with the chromosomes assuming their position at its equator
- mitosis is completed and the one cell zygote becomes a two cell embryo
Fertilisation summary
- Sperm enters oocyte causing Ca2+ waves
This causes:
- Cortical granules to fuse with ZP to block polyspermy
- nucleus of sperm to transform to male pronucleus
- completion of Meiosis II and expulsion of 2nd polar body –> formation of female pronucleus
- the 2 pronuclei come together, the membranes break down and there is alignment of chromosomes on the spindle = mitosis
How long after fertilisation does implantation occur?
- fertilisation occurs very close to the ampulla
- day 2 = 2 cells
- day 3 = 4 cells
- day 4 = morula
- inner cell mass is visible inside blastocyst
- spends around 4/ days in the uterine tube and then implants into the endometrium around day 7