The follicular phase, also known as the preovulatory phase or proliferative phase,
[ ] is the phase of the
estrous cycle (or, in primates for example, the
menstrual cycle
The menstrual cycle is a series of natural changes in hormone production and the structures of the uterus and ovaries of the female reproductive system that makes pregnancy possible. The ovarian cycle controls the production and release of eg ...
) during which
follicles in the
ovary
The ovary () is a gonad in the female reproductive system that produces ova; when released, an ovum travels through the fallopian tube/ oviduct into the uterus. There is an ovary on the left and the right side of the body. The ovaries are end ...
mature from primary follicle to a fully mature Graafian follicle. It ends with
ovulation
Ovulation is an important part of the menstrual cycle in female vertebrates where the egg cells are released from the ovaries as part of the ovarian cycle. In female humans ovulation typically occurs near the midpoint in the menstrual cycle and ...
. The main hormones controlling this stage are secretion of
gonadotropin-releasing hormone
Gonadotropin-releasing hormone (GnRH) is a releasing hormone responsible for the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary. GnRH is a tropic peptide hormone synthesized and rele ...
s, which are
follicle-stimulating hormones and
luteinising hormones. They are released by
pulsatile secretion.
[ The duration of the follicular phase can differ depending on the length of the menstrual cycle, while the ]luteal phase
The menstrual cycle is on average 28 days in length. It begins with Menstruation, menses (day 1–7) during the follicular phase (day 1–14), followed by ovulation (day 14) and ending with the luteal phase (day 14–28). While historically, medi ...
is usually stable, does not really change and lasts 14 days.
Hormonal events
Protein secretion
Due to the increase of FSH, the protein inhibin B will be secreted by the granulosa cells. Inhibin B will eventually blunt the secretion of FSH toward the end of the follicular phase. Inhibin B levels will be highest during the LH surge before ovulation and will quickly decrease after.[
]
Follicle recruitment
Follicle-stimulating hormone (FSH) is secreted by the anterior pituitary gland
A gland is a Cell (biology), cell or an Organ (biology), organ in an animal's body that produces and secretes different substances that the organism needs, either into the bloodstream or into a body cavity or outer surface. A gland may also funct ...
(Figure 2). FSH secretion begins to rise in the last few days of the previous menstrual cycle, and is the highest and most important during the first week of the follicular phase (Figure 1). The rise in FSH levels recruits five to seven tertiary-stage ovarian follicle
An ovarian follicle is a roughly spheroid cellular aggregation set found in the ovaries. It secretes hormones that influence stages of the menstrual cycle. In humans, women have approximately 200,000 to 300,000 follicles at the time of puberty, ea ...
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 cells in the developing follicles, and the expression of luteinizing hormone (LH) receptors on these granulosa cells (Figure 1). Under the influence of FSH, aromatase and p450 enzymes are activated, causing the granulosa cells to begin to secrete estrogen
Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...
. This increased level of estrogen stimulates production of gonadotropin-releasing hormone
Gonadotropin-releasing hormone (GnRH) is a releasing hormone responsible for the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary. GnRH is a tropic peptide hormone synthesized and rele ...
(GnRH), which increases production of LH. LH induces androgen
An androgen (from Greek ''andr-'', the stem of the word meaning ) is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This includes ...
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
The endometrium is the inner epithelium, epithelial layer, along with its mucous membrane, of the mammalian uterus. It has a basal layer and a functional layer: the basal layer contains stem cells which regenerate the functional layer. The funct ...
and myometrium of the uterus
The uterus (from Latin ''uterus'', : uteri or uteruses) or womb () is the hollow organ, organ in the reproductive system of most female mammals, including humans, that accommodates the embryonic development, embryonic and prenatal development, f ...
. It also causes endometrial cells to produce receptors for progesterone
Progesterone (; P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the ma ...
, 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
The endometrium is the inner epithelium, epithelial layer, along with its mucous membrane, of the mammalian uterus. It has a basal layer and a functional layer: the basal layer contains stem cells which regenerate the functional layer. The funct ...
in the uterus, histologically identified as the proliferative endometrium. Crypts in the cervix
The cervix (: cervices) or cervix uteri is a dynamic fibromuscular sexual organ of the female reproductive system that connects the vagina with the uterine cavity. The human female cervix has been documented anatomically since at least the time ...
are also stimulated to produce fertile cervical mucus. This mucus reduces the acidity of the vagina
In mammals and other animals, the vagina (: vaginas or vaginae) is the elastic, muscular sex organ, reproductive organ of the female genital tract. In humans, it extends from the vulval vestibule to the cervix (neck of the uterus). The #Vag ...
, creating a more hospitable environment for sperm
Sperm (: sperm or sperms) is the male reproductive Cell (biology), cell, or gamete, in anisogamous forms of sexual reproduction (forms in which there is a larger, female reproductive cell and a smaller, male one). Animals produce motile sperm ...
. It also has a characteristic texture that helps guide sperm through the cervix and to the fallopian tube
The fallopian tubes, also known as uterine tubes, oviducts or salpinges (: salpinx), are paired tubular sex organs in the human female body that stretch from the Ovary, ovaries to the uterus. The fallopian tubes are part of the female reproduct ...
s, where they wait for ovulation. In addition, 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 (Figure 1). 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 meiotic 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
Follicular waves are best described as the phase when follicles have matured sufficiently and rupture, leading to ovulation. Recent findings into the menstrual cycle in mammals has discovered that 2 or more follicles can develop but only one of the follicles fully matures to release the egg. This follicular wave involves multiple surges in the levels of FSH to initiate follicular development. A study has found that 68% of women tended to display two follicular wave developments before ovulation while the remaining had three waves.
References
{{Authority control
Reproductive system
Human female endocrine system