Follicular phase
Encyclopedia
The follicular phase is the phase of the estrous cycle
, (or, in humans and great apes, the menstrual cycle
) during which follicles in the ovary
mature. It ends with ovulation
. The main hormone controlling this stage is estradiol
.
(FSH) is secreted by the anterior pituitary
gland
. FSH secretion begins to rise in the last few days of the previous menstrual cycle, and is highest and most important during the first week of the follicular phase. The rise in FSH levels recruits five to seven tertiary-stage ovarian follicle
s (this stage follicle is also known as a Graafian follicle or antral
follicle) for entry into the menstrual cycle. These follicles, that have been growing for the better part of a year in a process known as folliculogenesis
, compete with each other for dominance.
FSH induces the proliferation of granulosa cell
s in the developing follicles, and the expression of luteinizing hormone
(LH) receptors on these granulosa cells. Under the influence of FSH, aromatase
and p450 enzymes are activated, causing the granulosa cells to begin to secrete estrogen
. This increased level of estrogen stimulates production of gonadotropin-releasing hormone
(GnRH), which increases production of LH. LH induces androgen
synthesis by thecal cells, stimulates proliferation, differentiation, and secretion of follicular thecal cells and increases LH receptor expression on granulosa cells.
Throughout the entire follicular phase, rising estrogen levels in the blood stimulates growth of the endometrium
and myometrium
of the uterus
. It also causes endometrial cells to produce receptors for progesterone
, which helps prime the endometrium to respond to rising levels of progesterone during the late proliferative phase and throughout the luteal phase.
These high estrogen levels initiate the formation of a new layer of endometrium
in the uterus, histologically identified as the proliferative endometrium. Crypts in the cervix
are also stimulated to produce fertile cervical mucus. This mucus reduces the acidity of the vagina
, creating a more hospitable environment for sperm
. It also has a characteristic texture that helps guide sperm through the cervix and to the fallopian tube
s, where they wait for ovulation. In addition, basal body temperature
may lower slightly under the influence of high estrogen levels.
division of the oocytes is completed. The surge also initiates luteinization of thecal and granulosa cells. Ovulation normally occurs 30 (± 2) hours after the beginning of the LH surge (when LH is first detectable in urine).
sources may refer to multiple waves of follicular development as a split peak because of the characteristic pattern of cervical mucus changes that is sometimes observed.
Estrous cycle
The estrous cycle comprises the recurring physiologic changes that are induced by reproductive hormones in most mammalian placental females. Estrous cycles start after puberty in sexually mature females and are interrupted by anestrous phases or pregnancies...
, (or, in humans and great apes, the menstrual cycle
Menstrual cycle
The menstrual cycle is the scientific term for the physiological changes that can occur in fertile women for the purpose of sexual reproduction. This article focuses on the human menstrual cycle....
) during which follicles in the ovary
Ovary
The ovary is an ovum-producing reproductive organ, often found in pairs as part of the vertebrate female reproductive system. Ovaries in anatomically female individuals are analogous to testes in anatomically male individuals, in that they are both gonads and endocrine glands.-Human anatomy:Ovaries...
mature. It ends with ovulation
Ovulation
Ovulation is the process in a female's menstrual cycle by which a mature ovarian follicle ruptures and discharges an ovum . Ovulation also occurs in the estrous cycle of other female mammals, which differs in many fundamental ways from the menstrual cycle...
. The main hormone controlling this stage is estradiol
Estradiol
Estradiol is a sex hormone. Estradiol is abbreviated E2 as it has 2 hydroxyl groups in its molecular structure. Estrone has 1 and estriol has 3 . Estradiol is about 10 times as potent as estrone and about 80 times as potent as estriol in its estrogenic effect...
.
Follicle recruitment
Follicle-stimulating hormoneFollicle-stimulating hormone
Follicle-stimulating hormone is a hormone found in humans and other animals. It is synthesized and secreted by gonadotrophs of the anterior pituitary gland. FSH regulates the development, growth, pubertal maturation, and reproductive processes of the body. FSH and Luteinizing hormone act...
(FSH) is secreted by the anterior pituitary
Anterior pituitary
A major organ of the endocrine system, the anterior pituitary, also called the adenohypophysis, is the glandular, anterior lobe of the pituitary gland...
gland
Gland
A gland is an organ in an animal's body that synthesizes a substance for release of substances such as hormones or breast milk, often into the bloodstream or into cavities inside the body or its outer surface .- Types :...
. FSH secretion begins to rise in the last few days of the previous menstrual cycle, and is highest and most important during the first week of the follicular phase. The rise in FSH levels recruits five to seven tertiary-stage ovarian follicle
Ovarian follicle
Ovarian follicles are the basic units of female reproductive biology, each of which is composed of roughly spherical aggregations of cells found in the ovary. They contain a single oocyte . These structures are periodically initiated to grow and develop, culminating in ovulation of usually a single...
s (this stage follicle is also known as a Graafian follicle or antral
Follicular antrum
The follicular antrum is the portion of an ovarian follicle filled with liquor folliculi.-External links: "Graafian Follicle" - "Mammal, canine ovary "*...
follicle) for entry into the menstrual cycle. These follicles, that have been growing for the better part of a year in a process known as folliculogenesis
Folliculogenesis
In biology, folliculogenesis is the maturation of the ovarian follicle, a densely-packed shell of somatic cells that contains an immature oocyte...
, compete with each other for dominance.
FSH induces the proliferation of granulosa cell
Granulosa cell
A granulosa cell or follicular cell is a somatic cell of the sex cord that is closely associated with the developing female gamete in the ovary of mammals.-Anatomy and function:...
s in the developing follicles, and the expression of luteinizing hormone
Luteinizing hormone
Luteinizing hormone is a hormone produced by the anterior pituitary gland. In females, an acute rise of LH called the LH surge triggers ovulation and development of the corpus luteum. In males, where LH had also been called interstitial cell-stimulating hormone , it stimulates Leydig cell...
(LH) receptors on these granulosa cells. Under the influence of FSH, aromatase
Aromatase
Aromatase is an enzyme responsible for a key step in the biosynthesis of estrogens. It is a member of the cytochrome P450 superfamily , which are monooxygenases that catalyze many reactions involved in steroidogenesis. In particular, aromatase is responsible for the aromatization of androgens into...
and p450 enzymes are activated, causing the granulosa cells to begin to secrete estrogen
Estrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
. This increased level of estrogen stimulates production of gonadotropin-releasing hormone
Gonadotropin-releasing hormone
Gonadotropin-releasing hormone , also known as Luteinizing-hormone-releasing hormone and luliberin, is a tropic peptide hormone responsible for the release of follicle-stimulating hormone and luteinizing hormone from the anterior pituitary. GnRH is synthesized and released from neurons within...
(GnRH), which increases production of LH. LH induces androgen
Androgen
Androgen, also called androgenic hormone or testoid, is the generic term for any natural or synthetic compound, usually a steroid hormone, that stimulates or controls the development and maintenance of male characteristics in vertebrates by binding to androgen receptors...
synthesis by thecal cells, stimulates proliferation, differentiation, and secretion of follicular thecal cells and increases LH receptor expression on granulosa cells.
Throughout the entire follicular phase, rising estrogen levels in the blood stimulates growth of the endometrium
Endometrium
-Function:The endometrium is the innermost glandular layer and functions as a lining for the uterus, preventing adhesions between the opposed walls of the myometrium, thereby maintaining the patency of the uterine cavity. During the menstrual cycle or estrous cycle, the endometrium grows to a...
and myometrium
Myometrium
The myometrium is the middle layer of the uterine wall, consisting mainly of uterine smooth muscle cells , but also of supporting stromal and vascular tissue...
of the uterus
Uterus
The uterus or womb is a major female hormone-responsive reproductive sex organ of most mammals including humans. One end, the cervix, opens into the vagina, while the other is connected to one or both fallopian tubes, depending on the species...
. It also causes endometrial cells to produce receptors for progesterone
Progesterone
Progesterone also known as P4 is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy and embryogenesis of humans and other species...
, which helps prime the endometrium to respond to rising levels of progesterone during the late proliferative phase and throughout the luteal phase.
Estrogen surge
Two or three days before LH levels begin to increase, usually by day seven of the cycle, one (or occasionally two) of the recruited follicles has emerged as dominant. Many endocrinologists believe that the estrogen secretion of the dominant follicle has increased to a level that GnRH production is suppressed, which lowers the levels of LH and FSH. This slowdown in LH and FSH production leads to the atresia (death) of most of the recruited follicles, though the dominant follicle continues to mature. Estrogen levels will continue to increase for several days (on average, six days, but this varies widely).These high estrogen levels initiate the formation of a new layer of endometrium
Endometrium
-Function:The endometrium is the innermost glandular layer and functions as a lining for the uterus, preventing adhesions between the opposed walls of the myometrium, thereby maintaining the patency of the uterine cavity. During the menstrual cycle or estrous cycle, the endometrium grows to a...
in the uterus, histologically identified as the proliferative endometrium. Crypts in the cervix
Cervix
The cervix is the lower, narrow portion of the uterus where it joins with the top end of the vagina. It is cylindrical or conical in shape and protrudes through the upper anterior vaginal wall...
are also stimulated to produce fertile cervical mucus. This mucus reduces the acidity of the vagina
Vagina
The vagina is a fibromuscular tubular tract leading from the uterus to the exterior of the body in female placental mammals and marsupials, or to the cloaca in female birds, monotremes, and some reptiles. Female insects and other invertebrates also have a vagina, which is the terminal part of the...
, creating a more hospitable environment for sperm
Spermatozoon
A spermatozoon is a motile sperm cell, or moving form of the haploid cell that is the male gamete. A spermatozoon joins an ovum to form a zygote...
. It also has a characteristic texture that helps guide sperm through the cervix and to the fallopian tube
Fallopian tube
The Fallopian tubes, also known as oviducts, uterine tubes, and salpinges are two very fine tubes lined with ciliated epithelia, leading from the ovaries of female mammals into the uterus, via the utero-tubal junction...
s, where they wait for ovulation. In addition, basal body temperature
Basal body temperature
Basal body temperature is the lowest temperature attained by the body during rest . It is generally measured immediately after awakening and before any physical activity has been undertaken, although the temperature measured at that time is somewhat higher than the true basal body temperature...
may lower slightly under the influence of high estrogen levels.
LH surge and ovulation
Estrogen levels are highest right before the LH surge begins. The short-term drop in steroid hormones between the beginning of the LH surge and the event of ovulation may cause mid-cycle spotting or bleeding. Under the influence of the preovulatory LH surge, the first meioticMeiosis
Meiosis is a special type of cell division necessary for sexual reproduction. The cells produced by meiosis are gametes or spores. The animals' gametes are called sperm and egg cells....
division of the oocytes is completed. The surge also initiates luteinization of thecal and granulosa cells. Ovulation normally occurs 30 (± 2) hours after the beginning of the LH surge (when LH is first detectable in urine).
Follicular waves
The time from recruitment of tertiary stage follicles to ovulation is normally about two weeks, comprising days 1-14 of an idealized 28-day menstrual cycle. However, it is common for the follicular phase to last much longer, as sometimes no dominant follicle is selected. In this case, normally more tertiary stage follicles are recruited and the process begins again. One study of women with regular menstrual cycles found that none of them ovulated after the first wave of follicle development: 68% of cycles showed ovulation after the second wave, while 32% of cycles showed ovulation after the third wave. Fertility awarenessFertility awareness
Fertility awareness refers to a set of practices used to determine the fertile and infertile phases of a woman's menstrual cycle. Fertility awareness methods may be used to avoid pregnancy, to achieve pregnancy, or as a way to monitor gynecological health....
sources may refer to multiple waves of follicular development as a split peak because of the characteristic pattern of cervical mucus changes that is sometimes observed.