ABNORMAL PAP SMEAR

The menstrual cycle refers to the regular changes in the activity of

the ovaries and the endometrium that make reproduction possible.
The 2 significance: a) Single ovum is normally release from ovaries each month.

b) Uterine endometrium is prepared in advance for implantation of the fertilized ovum at the required time of the month.

The endometrium is the layer of tissue lining the inside of the uterus.
This lining consists of a functional layer, which is subject to hormonal
changes and is shed during menstruation, and a thin basal layer which feeds the
overlying functional layer.
The menstrual cycle consists of two interconnected and synchronized processes:
1. OVARIAN CYCLE, which centers on the development of the ovarian
follicles and ovulation, and the
2. UTERINE OR ENDOMETRIAL CYCLE, which centers on the way in
which the functional endometrium thickens and sheds in response
to ovarian activity.
Menarche, which refers to the onset of the first menstrual period, usually
occurs during early adolescence as part of puberty.
Following menarche, the menstrual cycle recurs on a monthly basis, pausing
only during pregnancy, until a person reaches menopause, when her ovarian
function declines and she stops having menstrual periods.
The monthly menstrual cycle can vary in duration from 20 to 35 days, with an
average of 28 days. Each menstrual cycle begins on the first day of menstruation,
and this is referred to as day one of the cycle. Ovulation, or the release of the
oocyte from the ovary, usually occurs 14 days before the first day
of menstruation (i.e., 14 days before the next cycle begins). So, for an average
28-day menstrual cycle, this means that there are usually 14 days leading up
to ovulation (i.e., the preovulatory phase) and 14 days following ovulation (i.e.,
the postovulatory phase).
During these two phases, the ovaries and the endometrium each undergo their
own set of changes, which are separate but related. As a result, each phase of
the menstrual cycle has two different names to describe these two different
parallel processes. For the ovary, the two weeks leading up to ovulation is called
the ovarian follicular phase, and this corresponds to the menstrual and
proliferative phases of the endometrium. Similarly, the two weeks
following ovulation is referred to as the ovarian luteal phase, which also
corresponds to the secretory phase of the endometrium.

So, let’s first focus on the preovulatory period, starting with the ovarian follicular
phase. This phase starts on the first day of menstruation and represents weeks one
and two of a four-week cycle.
The whole menstrual cycle is controlled by the hypothalamus and the pituitary
gland, which are like the masterminds of reproduction.
The hypothalamus is a part of the brain that secretes gonadotropin-releasing
hormone, or GnRH, which causes the nearby anterior pituitary gland to release
follicle stimulating hormone, or FSH, and luteinizing hormone, or LH.
Before puberty, the gonadotropin-releasing hormone is released at a steady rate,
but once puberty hits, the gonadotropin-releasing hormone is released in pulses,
sometimes more and sometimes less.
The frequency and magnitude of the gonadotropin-releasing hormone pulses
determine how much follicle stimulating hormone and luteinizing hormone will
be produced by the pituitary.
These pituitary hormones control the maturation of the ovarian follicles, each of
which is initially made up of an immature sex cell, or primary oocyte,
surrounded by layers of theca and granulosa cells, the hormone-secreting cells
of the ovary.
Over the course of the follicular phase, these oocyte-containing groups of cells,
or follicles, grow and compete for a chance at ovulation.
During the first ten days, theca cells develop receptors and bind luteinizing
hormone, and in response secrete large amounts of the hormone
androstenedione, an androgen hormone.
Similarly, granulosa cells develop receptors and bind follicle stimulating
hormone, and in response produce the enzyme aromatase.
Aromatase converts androstenedione from the theca cells into 17β-estradiol,
which is a member of the estrogen family.
During days 10 through 14 of this phase, granulosa cells also begin to develop
luteinizing hormone receptors, in addition to the follicle stimulating hormone
receptors they already have.
As the follicles grow and estrogen is released into the bloodstream,
increased estrogen levels act as a negative feedback signal, telling
the pituitary to secrete less follicle stimulating hormone.
As a result of decreased follicle stimulating hormone production, some of the
developing follicles in the ovary will stop growing, regress and die off.
The follicle that has the most follicle stimulating hormone receptors, however,
will continue to grow, becoming the dominant follicle that will eventually
undergo ovulation.
This dominant follicle continues to secrete estrogen, and the
rising estrogen levels make the pituitary more responsive to the pulsatile action
of gonadotropin-releasing hormone from the hypothalamus.
As blood estrogen levels start to steadily climb higher and higher,
the estrogen from the dominant follicle now becomes a positive feedback signal
– that is, it makes the pituitary secrete a whole lot of follicle stimulating
hormone and luteinizing hormone in response to gonadotropin-releasing
hormone.
This surge of follicle stimulating hormone and luteinizing hormone usually
happens a day or two before ovulation and is responsible for stimulating the
rupture of the ovarian follicle and the release of the oocyte.
You can think of it this way: for most of the follicular phase, the pituitary saves
its energy, then when it senses that the dominant follicle ready for release,
the pituitary uses all its energy to secrete enough follicle stimulating hormone
and luteinizing hormone to induce ovulation.
While the ovary is busy preparing an egg for ovulation, the uterus, meanwhile,
is preparing the endometrium for implantation and maintenance of pregnancy.
This process begins with the menstrual phase, which is when the
old endometrial lining, or functional layer, from the previous cycle is shed and
eliminated through the vagina, producing the bleeding pattern known as
the menstrual period.
The menstrual phase lasts an average of five days and is followed by the
proliferative phase, during which high estrogen levels stimulate thickening of
the endometrium, growth of endometrial glands, and emergence of spiral
arteries, which grow a little under the influence of estrogen, from the basal layer
to feed the growing functional endometrium.
Rising estrogen levels also help change the consistency of the cervical mucus,
making it more hospitable to incoming sperm.
The combined effects of this spike in estrogen on the uterus and cervix help to
optimize the chance of fertilization, which is highest between day 11 and day 15
of an average 28-day cycle.
Following ovulation, the remnant of the ovarian follicle becomes the corpus
luteum, which is made up of luteinized theca and granulosa cells, meaning that
these cells have been exposed to the high luteinizing hormone levels that occur
just before ovulation.
Luteinized theca cells keep secreting androstenedione, and the luteinized
granulosa cells keep converting it to 17β-estradiol, as before.
However, luteinized granulosa cells also respond to the low luteinizing hormone
concentrations that are present after ovulation by increasing the activity
of cholesterol side-chain cleavage enzyme, or P450scc for short.
This enzyme converts more cholesterol to pregnenolone,
a progesterone precursor.
So luteinized granulosa cells secrete more progesterone than estrogen during
the luteal phase.
Progesterone acts as a negative feedback signal on the pituitary, decreasing
release of follicle stimulating hormone and luteinizing hormone.
At the same time, luteinized granulosa cells begin secreting inhibin, which
similarly inhibits the pituitary gland from making follicle stimulating hormone.
Both of these processes result in a decline in estrogen levels, meaning
that progesterone becomes the dominant hormone present during this phase of
the cycle.
Together with the decreased level of estrogen, the rising progesterone level
signals that ovulation has occurred and helps make the endometrium receptive
to the implantation of a fertilized gamete.
Under the influence of progesterone, the uterus enters into the secretory phase
of the endometrial cycle.
During this time spiral arteries grow the most and become coiled, and
the uterine glands begin to secrete more mucus.

After day 15 of the cycle, the optimal window for fertilization begins to close.
The cervical mucus starts to thicken and becomes less hospitable to the sperm.
Over time, the corpus luteum gradually degenerates into the nonfunctional
corpus albicans.
The corpus albicans doesn’t make hormones, so estrogen and
progesterone levels slowly decrease.
When progesterone reaches its lowest level, the spiral arteries collapse, and the
functional layer of the endometrium prepares to shed through menstruation.
This shedding marks the beginning of a new menstrual cycle and another
opportunity for fertilization.
Summary
All right, so as a quick recap - the menstrual cycle begins on the first day
of menstruation.
For an average 28-day menstrual cycle, the changes which occur in
the ovary during the first 14 days are called the follicular phase.
Ovulation usually occurs at day 14, as a result of the estrogen-induced surge in
luteinizing hormone.
The last 14 days of the cycle are the luteal phase, during
which progesterone becomes the dominant hormone.
While the length of the follicular phase can vary, the luteal phase almost always
precedes the onset of menses by 14 days.
The uterus also goes through its own set of changes.
During the first 14 days of the cycle, the endometrium goes through
the menstrual phase and the proliferative phase, and during the last 14 days it
goes through the secretory phase.