EAST 501 Lecture Notes - Lecture 7: Granulosa Cell, Abvd, Assisted Reproductive Technology
21 Jun 2018
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Jan 24th – Lec 7 Bernard
Female Infertility: Ovarian Aging & Aneuploidy
-fertility decline happens in several phases
omenopause usually occurs ~50yo occurs because
oocytes in the cortex of the ovaries run out and
there is too little E2 to drive the reproductive
cycles leads to total sterility in effect
-female fertility declines long before menopause
oin late 30s becomes statistically more difficult to
get pregnant this phase of the reproductive
decline that we are talking about; still having a
period, but less fertile
OOCYTRES ARE STORED IN OVARIAN FOLLICLES
-oocyte: the female gamete = “pre-egg” at any stages in development
-the term “egg” you can only use to describe a certain point in the gamete development at metaphase II
-an egg is a type of oocyte, but not all oocytes are eggs
-in the cortex of the ovaries there are primordial oocytes that are waiting to be ovulated would need to grow
before, during follicle recruitment (physical increase in size of the oocyte and a proliferation of the granulosa
cells)
-one layer of granulosa cells of the oocyte = primary follicle
-secondary follicle = multiple layers of granulosa cells
-ultimately the follicles form a fluid filled antrum = graphian follicle/antral follicle (in other species)
THE MENOPAUSE: LOSS OF FOLLICLES FROM THE OVARY
-there is a linear decline until ~37yo, then there is a drop off around the late 30s there is a more rapid decline in
the number of follicles
-median age of onset of menopause ~50yo
OOCYTE NEOGENESIS? QUESTIONAING A CENTRAL DOGMA OF REPRODUCTIVE BIOLOGY
-“Germline stem cells and follicular renewal in the postnatal mammalian ovary”
-this is no longer a cut and dry question
IS IT POSSIBLE THAT A PHARMACOLOGICAL AGENT MIGHT INCREASE OOCYTE NUMBER? DELAY MENOPUASE?
-Group in Scotland: “Non-growing follicle density is increased following adriamycin, bleocymin, vinblastine and
decarbazine (ABVD) chemotherapy in the adult human ovary
othey opposed that stem cells in the ovaries that make more oocytes originally, now they kind there may
be stem cells
othey took pieces of ovaries that were biopsied from patients that were given different
chemotherapeutic agents
with a certain combination of therapeutics, the number of oocytes that are found after the
therapy is far greater than what was expected
suggested that a certain cocktail of chemotherapeutics can actually increase the number of
oocytes/germ cells
the number of oocytes in the cortex at the time of birth is all that you will ever had is not as set
in stone anymore
othe patients who received ABVD had much greater mean non-growing follicle density than the model-
predicted values from ages 10 through 50
find more resources at oneclass.com
find more resources at oneclass.com
Jan 24th – Lec 7 Bernard
Female Infertility: Ovarian Aging & Aneuploidy
EVIDENCE THAT OOCYTE QUALITY DECREASES WITH AGE
-as your fertility decrease the likelihood of having a spontaneous abortion increases almost exactly inversely
othis data was collected in a community where females are pressed to have many children
oif instead if you measure all conceptuses (all that make it to term and those who miscarry) if you
compare the number of chromosomes in the cell to the maternal age, if it more likely that the
chromosome number will be higher in the older moms embryos far more likely to be aneuploid if the
mom is older and most aneuploid embryos are not compatible with life
-the rate of fertility and rate of spontaneous abortion is hard to measure because many pregnancies that are
aneuploid may be miscarried before the mom even knew that she was pregnant = occucled pregnancies
-the reduction is infertility is related to the embryo having the wrong number of chromosomes
PRECENTAGES OF TRANSFERS THAT RESULTED IN LIVE BIRTHS FOR
ART CYCLES USING FRESH EMBRYOS FROM OWN AND DONOR EGGS
-the above data is an amalgamation of data or women who are going for fertility treatment women going for
routine fertility treatment
-the likelihood of success decreases markedly in the mid-30s years
-similar women are going for the treatment, but instead of using their own eggs they are using donor eggs from
young healthier women think that the egg is the root of the age related decline in fertility
othe age related difference is now completely lost
find more resources at oneclass.com
find more resources at oneclass.com
Jan 24th – Lec 7 Bernard
Female Infertility: Ovarian Aging & Aneuploidy
OOCYTE GENETIC INTEGRITY DECREASES WITH MATERNAL AGE
-there is an increased risk of trisomy
-oocyte maturation (MEIOSIS I) occurs over the course of
~10 hours (mice) – the division of the egg and polar body
oin younger women this process is quite faithful
the likelihood that the chromosomes are being
segregated properly and that the cells will be euploidy is
high
-meiosis I = oocyte maturation
-successful pregnancy becomes difficult in the 30’s and 40’s because the
probability of the egg having the wrong number of chromosomes
increases
SO, WHAT GOES WRONG IN THE OOCYTE SPECIFICALLY THAT CAUSES IT TO BE MORE LIKELY TO BE ANUEPLOID IN
OLDER FEMALES?
-during the 36 hour maturation (humans) there is an LH surge which triggers ovulation (meiosis I)
THE CAUSE OF THE PROBLEM – CHROMOSOME SEGREGATION IN THE OOCYTE
-the part of the cell that is controlling the chromosome segregation = spindles
ochromosome segregated into the polar body and the oocyte
omicrotubules make up the spindles make sure that the chromosomes go to the right daughter cells
CHROMOSOME SEGREGATION (VERY) SIMPLIFIED
-there is a signaling network that involves a complicated array of proteins ensures that anaphase can take place
-the spindles can pull the chromosomes into the two daughter cells
-the chromosomes are shown in blue
-kinetochores: complex big protein structures assemble on the centromeres of the chromosomes
-cohesins: keep the 2 chromosomes together
obefore anaphase takes place hold the two chromatids together
-the chromosome segregation usually goes right and cells usually manage to inherit the right number of
chromosomes because of the signaling network, the spindle assembly network (complicated array of proteins
that need to make sure that at metaphase the chromosomes are lined up correctly)
oif the chromosomes are not lines up correctly, make sure that anaphase cannot take place
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
The menopause: loss of follicles from the ovary there is a linear decline until ~37yo, then there is a drop off around the late 30s there is a more rapid decline in the number of follicles. Median age of onset of menopause ~50yo. Germline stem cells and follicular renewal in the postnatal mammalian ovary this is no longer a cut and dry question. Precentages of transfers that resulted in live births for. Oocyte genetic integrity decreases with maternal age there is an increased risk of trisomy oocyte maturation (meiosis i) occurs over the course of. Meiosis i = oocyte maturation successful pregnancy becomes difficult in the 30"s and 40"s because the probability of the egg having the wrong number of chromosomes increases. So, what goes wrong in the oocyte specifically that causes it to be more likely to be anueploid in. Older females? during the 36 hour maturation (humans) there is an lh surge which triggers ovulation (meiosis i)
