Atresia Flashcards
Oogonia that do not form primordial follicles will
degenerate by the process of atresia.
As a result, only approximately ________ primordial follicles with primary oocytes will be present at birth.
Two million
From birth to puberty the primary oocytes remain in
the resting state (meiosis I).
However, a proportion of the follicles either do not become arrested, do not stay arrested, or initiate growth during prenatal or pre-pubertal life when they are destined to become atretic due to
the immaturity of the hypothalamo-pituitary.
The loss of primordial follicles is initiated by
the death of the oocyte and this process of random atresia continues during childhood and into the pre-adolescence years.
By the time puberty is reached, the total number of oocytes within the ovary
has dropped to 300,000-400,000.
The process of oocyte atresia is not well understood although there is evidence to suggest that
programmed cell death (apoptosis) is involved in follicular atresia in the human ovary.
Apoptosis has been shown to occur in human fetal ovaries from
gestational week 13 onwards.
However, unlike the apoptotic death of embryonic germ cells and pre-meiotic oogonia
the demise of primordial follicles
Follicle atresia is a continuous process that starts
around the 20th week of gestation and continues throughout the life of the woman.
99.99% of primordial follicles never mature, they
degenerate and are reabsorbed by the body.
The process continues until all of the oocytes are depleted at
45 to 55 years of age and is the cause of menopause.
Ovarian aging is closely tied to the decline in
ovarian follicular reserve and oocyte quality.
Ovarian age cannot be assumed to correlate with
chronological age.
The bulk of oocytes laid down in the fetal ovary are lost before
birth and most of the rest before puberty.
However, oocyte selection for degradation does not
appear to be based on quality.
Many mature human oocytes carry anomalies that may impair their ultimate developmental potential and
the incidence of abnormal oocytes increases with maternal age.
Several hypotheses have been proposed to explain the origin of this maternal age affect based on the timing of meiotic entry of the oocyte during
fetal development (oocytes entering meiosis later may be more likely to succumb to DNA damage), oxidative damage, telomere and mitochondria function, ovarian mosaicism, aging of the ovarian environment within which the oocytes mature.
The analysis of human oocyte integrity appears to be further complicated by the impact of
genetic background on aspects of oogenesis.
Other evidence suggests that the internal environment of the mother during pregnancy at key stages of fetal ovary development may influence the extent of
oocyte selection and apoptosis directly affecting the fertility of her daughter by controlling the size of the ovarian reserve and the quality of the oocyte that will become her future grandchild.
Regulation of primordial follicle survival, loss and activation is
poorly understood and an area of active investigation.
The dormancy of primordial follicles is, unsurprisingly,
maintained by many factors.
Studies investigating the identity of the molecules with a role in the regulation of these
processes indicate two main pathways are involved.
These two pathways are:
> the phosphatase and tensin homolog (PTEN) I phosphatidylinositol-3 kinase (PI3K) / 3-phosphoinositide-dependent protein kinase-1 (PDPKI) I v-akt murine thymoma viral oncogene homolog 1 (AKT-1) that is activated by various hormones growth factors
> the bone morphogenic protein (BMP) I antimüllerian hormone (AMH) / SMAD signaling pathways
These data are mostly derived from animal models and as such may or may not be descriptive of
regulatory mechanisms in the human.
Under- or over-activation of these pathways may lead to
pathological conditions in the ovary including premature ovarian failure (POF) and infertility.
Insulin, insulin-like growth factors (IGF) and KITL (Kit ligand) are known to be key regulating factors of the survival and differentiation of germ and somatic ovarian cells. KITL along with basic fibroblast growth factor (bFGF) and keratinocyte growth factor (KGF) are known stimulators of the primordial to primary follicle transition whose actions are
inhibited by AMH.
The regulation of folliculogenesis has also been shown to involve many factors identified as
regulators of fetal ovarian development and maintenance of the pool of primordial follicles for example WNT4 and growth and differentiation factor 9 (GDF-9).
