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The follicular phase, also known as the preovulatory phase or proliferative phase, is the phase of the
estrous cycle The estrous cycle (, originally ) is the set of recurring physiological changes that are induced by reproductive hormones in most mammalian therian females. Estrous cycles start after sexual maturity in females and are interrupted by anestro ...
(or, in primates for example, the menstrual cycle) during which follicles in the ovary mature from primary follicle to a fully mature graafian follicle. It ends with
ovulation Ovulation is the release of eggs from the ovaries. In women, this event occurs when the ovarian follicles rupture and release the secondary oocyte ovarian cells. After ovulation, during the luteal phase, the egg will be available to be fertilize ...
. 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 release ...
s, which are follicle-stimulating hormones and luteinising hormones. They are released by
pulsatile secretion Pulsatile secretion is a Biochemistry, biochemical phenomenon observed in a wide variety of Cell (biology), cell and Tissue (biology), tissue types, in which Chemical substance, chemical products are secreted in a regular temporal pattern. The mos ...
. The duration of the follicular phase can differ depending on the length of the menstrual cycle, while the
luteal phase The corpus luteum (Latin for "yellow body"; plural corpora lutea) is a temporary endocrine structure in female ovaries involved in the production of relatively high levels of progesterone, and moderate levels of estradiol, and inhibin A. It is th ...
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 (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. At the time of puberty, women have approximately 200,000 to 300,000 follicles, each with t ...
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 :''Although the process is similar in many animals, this article will deal exclusively with human folliculogenesis.'' In biology, folliculogenesis is the maturation of the ovarian follicle, a densely packed shell of somatic cells that contains a ...
, compete with each other for dominance. FSH induces the proliferation of
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 (called an oocyte or egg) in the ovary of mammals. Structure and function In the primordial ovarian follicle, and la ...
s in the developing follicles, and the expression of
luteinizing hormone Luteinizing hormone (LH, also known as luteinising hormone, lutropin and sometimes lutrophin) is a hormone produced by gonadotropic cells in the anterior pituitary gland. The production of LH is regulated by gonadotropin-releasing hormone (GnRH) ...
(LH) receptors on these granulosa cells (Figure 1). Under the influence of FSH,
aromatase Aromatase (), also called estrogen synthetase or estrogen synthase, is an enzyme responsible for a key step in the biosynthesis of estrogens. It is CYP19A1, a member of the cytochrome P450 superfamily, which are monooxygenases that catalyze many ...
and
p450 Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various compo ...
enzymes are activated, causing the granulosa cells to begin to secrete
estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal ac ...
. 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 release ...
(GnRH), which increases production of LH. LH induces
androgen An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This in ...
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 The myometrium is the middle layer of the uterine wall, consisting mainly of uterine smooth muscle cells (also called uterine myocytes) but also of supporting stromal and vascular tissue. Its main function is to induce uterine contractions. Struc ...
of the
uterus The uterus (from Latin ''uterus'', plural ''uteri'') or womb () is the organ in the reproductive system of most female mammals, including humans that accommodates the embryonic and fetal development of one or more embryos until birth. The ...
. 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.


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 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 In mammals, the vagina is the elastic, muscular part of the female genital tract. In humans, it extends from the vestibule to the cervix. The outer vaginal opening is normally partly covered by a thin layer of mucosal tissue called the hymen ...
, creating a more hospitable environment for sperm. It also has a characteristic texture that helps guide sperm through the cervix and to the fallopian tubes, 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 Luteinizing hormone (LH, also known as luteinising hormone, lutropin and sometimes lutrophin) is a hormone produced by gonadotropic cells in the anterior pituitary gland. The production of LH is regulated by gonadotropin-releasing hormone (GnRH) ...
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 An oocyte (, ), oöcyte, or ovocyte is a female gametocyte or germ cell involved in reproduction. In other words, it is an immature ovum, or egg cell. An oocyte is produced in a female fetus in the ovary during female gametogenesis. The female g ...
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