4 Meiosis

Eggs often have too many or too few chromosomes = aneuploidy

The defects usually result in a failed implantation of the Fetus.

Cell division

• sperarion of chromosome arms by the spindle

• 1 Diploid cell -> 2 identical diploid cells

In males, meiosis I and meiosis II lead to the formation of four haploid gametes (sperm)

• continuous production

• 1 dipoid cell -> 4 haploid cells (gametes)

Female meiosis starts in the fetal embryo and only ends in the adult female

• the oocytes are already stored in the ovarian reserve in the fetal ovary

• In puberty, Follicle stimulating hormone and Luteinizing hormone lead to maturation of the oocytes in the adult ovary

• a sheath of follicular cells forms around the egg to feed it (primordial follicles -> Primary follicles -> secondary follicles) -> ripe oocyte

• A drastically increase in the Luteneizing hormone causes meiosis to continue

• In the Ovulation the follicle pushes out the egg. Meanwhile the egg gets rid of one copy of the chromosomes

• Egg is ready for fertilisation

• In female meiosis, the oocyte produces only one haploid germ cell (the egg)

• The extra chromosomes are discharged in two small cells termed polar bodies

• The polar bodies are degraded soon after their extrusion

• Oocytes often eliminate too few or too many chromosomes into the polar bodies

Homologous chromosomes are paired in the female embryo through meiotic recombination

• Chiasma are formed during meiotic recombination

• They provide a physical ink between homologous chromosomes

• This link is essential for accurate chromosome segregation during the first meiotic division, when the homologous chromosomes instead of sister chromatids are segregated

• Chiasmata increase the genetic diversity: mixture of chromosomes

• Leptotene: Protein SPO11 induces doublestrand breaks (DSB)

• Usually 1-2 crossovers

• Zygotene: After break, chromosomes can find each other based on DNA sequence

  • A synaptonemal complex can be formed. Like a sipper which is closed.

• Pachytene: the chromosomes are sipped together and the Synapsis is complete. Now the crossing over can occur

• Diplotene: the synaptonemal complex disappears to make the chiasma visible

• Diakinesis: Bivalents are ready for the metaphase

• the synaptonemal complex is formed by cohesin, axial cores and filaments

• Homologous chromosomes are separated during meiosis I, and sister chromatids during meiosis II

• the cohesine complex functions like glue to hold the homologous chromosomes together while meiotic recombination/crossover happens

Mitotic cohesine

• contain a heterodimer of Smc1 and Smc3

• Contain non-SMC subunit sister chromatid cohesin3 (Scc3)

• Contain an Alpha-kleisin subunit (Scc1)

Meiotic cohesine

• Alpha-kleisin Rec8 instead of Scc1

• Rec8 has meiosis specific functions

  • establishing the synaptonemal complex

• Shugoshin–PP2A (Sgo) complex protects pericentromeric cohesin during meiosis I

• Chromatids segregate (trennen) prematurely in Shugoshin mutants during meiosis II

• Sgo recruits and forms a complex with protein phosphatase 2A (PP2A) at centromeres

• The mis-segregation of homologous chromosomes

• The Premature separation of sister chromaids

• The reverse segregation: sister chromatids of homologous chromosomes separate as in mitosis

Age independent

• Spindles in mammalian oocytes lack centrosomes

• oocytes use different mechanisms for nucleating microtubules and focusing the spindle poles

• Low levels of the spindle stabilizing factor KIFC1 lead to spindle instability in human oocytes

Age independent

• In mitosis, the spindle assembly checkpoint (SAC) delays progression into anaphase until all chromosomes are attached to microtubules and aligned on the metaphase plate

• But oocytes frequently progress into Anaphase, even if chromosomes are misaligned => spindle assembly checkpoint might be leaky

• The spindle assembly checkpoint monitors bivalent and sister chromatid bi-orientation

age independent

• causes chromosome segregation errors -> promotes aneuploidy

• Because of the low cortical tension, the myosin 2 is very active and hinders the microtubules sterically

Age independent

• high fat diet/ obesity cause chromosome segregation errors and changes in transcription in oocytes

• Caloric restriction protects oocytes

• Environmental toxins like phthalates or bisphenol A (BPA) harms oocytes

  • Occurs in plastic products

  • May disrupt endocrine pathways and impair folliculogenesis and ovulation

  • Cause chromosome segregation errors in oocytes

• From the age of 32, the aneuploidy increases dramatically

• Then also ivf is insufficient

• Women are born with all oocytes -> chromosomes are very old

• With age there comes a loss of cohesine which binds the chromosomes

• The premature separation of sister chromatids (PSSC) is a leading cause of age-related female aneuploidy

• architecture of MI chromosomes (bivalents) changes with age -> sister kinetochores become unpaired

• changes in chromosomes architecture cause incorrect kinetochore-microtubule attachments

  • Meiosis 1: Unpaired sister kinetochores promote rotation of bivalents on spindle and moerotelic attachements

  • Meiosis 2: Sister kinetochore fragmentation promotes merotelic attachments