Follicular phase

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Follicular phase
MenstrualCycle2 en.svg
Figure 1. Menstrual cycle illustrating hormone levels, follicle development and uterine cycle
Biological system Urogenital system(reproductive)

The follicular phase, also known as the preovulatory phase or proliferative phase, [1] is the phase of the estrous cycle (or, in primates [2] 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. The main hormones controlling this stage are secretion of gonadotropin-releasing hormones, which are follicle-stimulating hormones and luteinising hormones. They are released by pulsatile secretion. [1] The duration of the follicular phase can differ depending on the length of the menstrual cycle, while the luteal phase is usually stable, does not really change and lasts 14 days.

Contents

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. [1]

Follicle recruitment

Figure 2. Follicular phase diagram of hormones and their origins Follicular phase diagram - early and late.png
Figure 2. Follicular phase diagram of hormones and their origins

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, [3] and is the highest and most important during the first week of the follicular phase [4] (Figure 1). The rise in FSH levels recruits five to seven tertiary-stage ovarian follicles (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. [5]

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. This increased level of estrogen stimulates production of gonadotropin-releasing hormone (GnRH), which increases production of LH. [4] LH induces androgen synthesis by thecal cells, stimulates proliferation, differentiation, and secretion of follicular thecal cells and increases LH receptor expression on granulosa cells. [4]

Throughout the entire follicular phase, rising estrogen levels in the blood stimulates growth of the endometrium and myometrium of the uterus. [6] It also causes endometrial cells to produce receptors for progesterone, [6] 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, [7] usually by day seven of the cycle, [8] 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). [7]

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. [7] This mucus reduces the acidity of the vagina, creating a more hospitable environment for sperm. [9] It also has a characteristic texture that helps guide sperm through the cervix [10] and to the fallopian tubes, where they wait for ovulation.[ medical citation needed ] In addition, basal body temperature may lower slightly under the influence of high estrogen levels. [11]

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. [12] 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. [4] Ovulation normally occurs 30 (± 2) hours after the beginning of the LH surge (when LH is first detectable in urine). [13]

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. [14] [15] 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. [16]

Related Research Articles

<span class="mw-page-title-main">Menstrual cycle</span> Natural changes in the human female reproductive system

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 eggs and the cyclic release of estrogen and progesterone. The uterine cycle governs the preparation and maintenance of the lining of the uterus (womb) to receive an embryo. These cycles are concurrent and coordinated, normally last between 21 and 35 days, with a median length of 28 days, and continue for about 30–45 years.

<span class="mw-page-title-main">Ovulation</span> Release of egg cells from the ovaries

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 fertilized by sperm. In addition, the uterine lining (endometrium) is thickened to be able to receive a fertilized egg. If no conception occurs, the uterine lining as well as the egg will be shed during menstruation.

Mittelschmerz is a colloquial term for "ovulation pain" or "midcycle pain". About 20% of women experience mittelschmerz, some every cycle, some intermittently.

<span class="mw-page-title-main">Luteinizing hormone</span> Gonadotropin secreted by the adenohypophysis

Luteinizing hormone is a hormone produced by gonadotropic cells in the anterior pituitary gland. The production of LH is regulated by gonadotropin-releasing hormone (GnRH) from the hypothalamus. In females, an acute rise of LH known as an LH surge, triggers ovulation and development of the corpus luteum. In males, where LH had also been called interstitial cell–stimulating hormone (ICSH), it stimulates Leydig cell production of testosterone. It acts synergistically with follicle-stimulating hormone (FSH).

<span class="mw-page-title-main">Follicle-stimulating hormone</span> Gonadotropin that regulates the development of reproductive processes

Follicle-stimulating hormone (FSH) is a gonadotropin, a glycoprotein polypeptide hormone. FSH is synthesized and secreted by the gonadotropic cells of the anterior pituitary gland and regulates the development, growth, pubertal maturation, and reproductive processes of the body. FSH and luteinizing hormone (LH) work together in the reproductive system.

<span class="mw-page-title-main">Corpus luteum</span> Temporary endocrine structure in ovaries

The corpus luteum 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 the remains of the ovarian follicle that has released a mature ovum during a previous ovulation.

<span class="mw-page-title-main">Ovarian follicle</span> Structure containing a single egg cell

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 the potential to release an egg cell (ovum) at ovulation for fertilization. These eggs are developed once every menstrual cycle with around 450–500 being ovulated during a woman's reproductive lifetime.

<span class="mw-page-title-main">Granulosa cell</span>

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.

The estrous cycle is a set of recurring physiological changes induced by reproductive hormones in females of mammalian subclass Theria. Estrous cycles start after sexual maturity in females and are interrupted by anestrous phases, otherwise known as "rest" phases, or by pregnancies. Typically, estrous cycles repeat until death. These cycles are widely variable in duration and frequency depending on the species. Some animals may display bloody vaginal discharge, often mistaken for menstruation. Many mammals used in commercial agriculture, such as cattle and sheep, may have their estrous cycles artificially controlled with hormonal medications for optimum productivity. The male equivalent, seen primarily in ruminants, is called rut.

<span class="mw-page-title-main">Folliculogenesis</span> Process of maturation of primordial follicles

In biology, folliculogenesis is the maturation of the ovarian follicle, a densely packed shell of somatic cells that contains an immature oocyte. Folliculogenesis describes the progression of a number of small primordial follicles into large preovulatory follicles that occurs in part during the menstrual cycle.

<span class="mw-page-title-main">Hypothalamic–pituitary–gonadal axis</span> Concept of regarding the hypothalamus, pituitary gland and gonadal glands as a single entity

The hypothalamic–pituitary–gonadal axis refers to the hypothalamus, pituitary gland, and gonadal glands as if these individual endocrine glands were a single entity. Because these glands often act in concert, physiologists and endocrinologists find it convenient and descriptive to speak of them as a single system.

<span class="mw-page-title-main">Luteal phase</span> The latter part of the menstrual cycle associated with ovulation and an increase in progesterone

The menstrual cycle is on average 28 days in length. It begins with menses during the follicular phase, followed by ovulation and ending with the luteal phase. Unlike the follicular phase which can vary in length among individuals, the luteal phase is typically fixed at approximately 14 days and is characterized by changes to hormone levels, such as an increase in progesterone and estrogen levels, decrease in gonadotropins such as follicle-stimulating hormone (FSH) and luteinizing hormone (LH), changes to the endometrial lining to promote implantation of the fertilized egg, and development of the corpus luteum. In the absence of fertilization by sperm, the corpus luteum atrophies leading to a decrease in progesterone and estrogen, an increase in FSH and LH, and shedding of the endometrial lining (menses) to begin the menstrual cycle again.

<span class="mw-page-title-main">Follicular atresia</span>

Follicular atresia refers to the process in which a follicle fails to develop, thus preventing it from ovulating and releasing an egg. It is a normal, naturally occurring progression that occurs as mammalian ovaries age. Approximately 1% of mammalian follicles in ovaries undergo ovulation and the remaining 99% of follicles go through follicular atresia as they cycle through the growth phases. In summary, follicular atresia is a process that leads to the follicular loss and loss of oocytes, and any disturbance or loss of functionality of this process can lead to many other conditions.

Ovulation induction is the stimulation of ovulation by medication. It is usually used in the sense of stimulation of the development of ovarian follicles to reverse anovulation or oligoovulation.

The theca folliculi comprise a layer of the ovarian follicles. They appear as the follicles become secondary follicles.

Poor ovarian reserve is a condition of low fertility characterized by 1): low numbers of remaining oocytes in the ovaries or 2) possibly impaired preantral oocyte development or recruitment. Recent research suggests that premature ovarian aging and premature ovarian failure may represent a continuum of premature ovarian senescence. It is usually accompanied by high FSH levels.

<span class="mw-page-title-main">Fertility testing</span>

Fertility testing is the process by which fertility is assessed, both generally and also to find the "fertile window" in the menstrual cycle. General health affects fertility, and STI testing is an important related field.

Follicle-stimulating hormone (FSH) insensitivity, or ovarian insensitivity to FSH in females, also referable to as ovarian follicle hypoplasia or granulosa cell hypoplasia in females, is a rare autosomal recessive genetic and endocrine syndrome affecting both females and males, with the former presenting with much greater severity of symptomatology. It is characterized by a resistance or complete insensitivity to the effects of follicle-stimulating hormone (FSH), a gonadotropin which is normally responsible for the stimulation of estrogen production by the ovaries in females and maintenance of fertility in both sexes. The condition manifests itself as hypergonadotropic hypogonadism, reduced or absent puberty, amenorrhea, and infertility in females, whereas males present merely with varying degrees of infertility and associated symptoms.

Gonadotropin surge-attenuating factor (GnSAF) is a nonsteroidal ovarian hormone produced by the granulosa cells of small antral ovarian follicles in females. GnSAF is involved in regulating the secretion of luteinizing hormone (LH) from the anterior pituitary and the ovarian cycle. During the early to mid-follicular phase of the ovarian cycle, GnSAF acts on the anterior pituitary to attenuate LH release, limiting the secretion of LH to only basal levels. At the transition between follicular and luteal phase, GnSAF bioactivity declines sufficiently to permit LH secretion above basal levels, resulting in the mid-cycle LH surge that initiates ovulation. In normally ovulating women, the LH surge only occurs when the oocyte is mature and ready for extrusion. GnSAF bioactivity is responsible for the synchronised, biphasic nature of LH secretion.

Ovarian follicle dominance is the process where one or more follicles are selected per cycle to ovulate.

References

  1. 1 2 3 Carol N. Monis; Maggie Tetrokalashvili. (2019). "Menstrual Cycle Proliferative And Follicular Phase". Treasure Island (FL): StatPearls Publishing. PMID   31194386. Creative Commons by small.svg  This article incorporates text available under the CC BY 4.0 license.
  2. ↑ "Primate | Definition, Biology, & Facts | Britannica". 3 January 2024.
  3. ↑ Reed, Beverly G.; Carr, Bruce R. (2000). "The Normal Menstrual Cycle and the Control of Ovulation". In De Groot, Leslie J.; Chrousos, George; Dungan, Kathleen; Feingold, Kenneth R.; Grossman, Ashley; Hershman, Jerome M.; Koch, Christian; Korbonits, Márta; McLachlan, Robert (eds.). Endotext. South Dartmouth (MA): MDText.com, Inc. PMID   25905282.
  4. 1 2 3 4 Dee Unglaub Silverthorn (2004). Human physiology: an integrated approach (Third ed.). San Francisco: Pearson/Benjamin Cummings. Chapter 26: Reproduction and Development, and Chapter 23 Endocrine control of growth and metabolism. ISBN   0-13-102015-3.
  5. ↑ McGee, E.A., & Hsueh, A.J. (2000). Initial and cyclic recruitment of ovarian follicles. Endocrine Reviews, 200-214, 21(2). doi: 10.1210/edrv.21.2.0394
  6. 1 2 Strang, Eric P. Widmaier, Hershel Raff, Kevin T. (2006). Vander's human physiology the mechanisms of body function (10th ed.). Boston: McGraw-Hill. p. 678. ISBN   0-07-111677-X.{{cite book}}: CS1 maint: multiple names: authors list (link)
  7. 1 2 3 Weschler, Toni (2002). Taking Charge of Your Fertility (Revised ed.). New York: HarperCollins. pp.  359–361. ISBN   0-06-093764-5.
  8. ↑ Stenchever Droegemuller Herbst Mishell (2001). Comprehensive Gynecology (Fourth ed.). St. Louise, Missouri: Mosby. p. 87. ISBN   0-323-01402-X.
  9. ↑ Weschler (2002), p.57
  10. ↑ Weschler (2002), illustrations p.59 and p.3 of color insert
  11. ↑ Weschler (2002), pp.54,306,310
  12. ↑ Weschler (2002), p.65
  13. ↑ Susan B. Bullivant; Sarah A. Sellergren; Kathleen Stern; et al. (February 2004). "Women's sexual experience during the menstrual cycle: identification of the sexual phase by noninvasive measurement of luteinizing hormone". Journal of Sex Research . 41 (1): 82–93. doi:10.1080/00224490409552216. PMID   15216427. S2CID   40401379.
  14. ↑ Evans, A. C.; Duffy, P.; Hynes, N.; Boland, M. P. (February 2000). "Waves of follicle development during the estrous cycle in sheep". Theriogenology. 53 (3): 699–715. doi:10.1016/S0093-691X(99)00268-X. ISSN   0093-691X. PMID   10735037.
  15. ↑ Boer, H. M. T.; Röblitz, S.; Stötzel, C.; Veerkamp, R. F.; Kemp, B.; Woelders, H. (December 2011). "Mechanisms regulating follicle wave patterns in the bovine estrous cycle investigated with a mathematical model". Journal of Dairy Science. 94 (12): 5987–6000. doi: 10.3168/jds.2011-4400 . ISSN   1525-3198. PMID   22118087.
  16. ↑ Baerwald, Angela R.; Adams, Gregg P.; Pierson, Roger A. (2003-09-01). "Characterization of Ovarian Follicular Wave Dynamics in Women1". Biology of Reproduction. 69 (3): 1023–1031. doi: 10.1095/biolreprod.103.017772 . ISSN   0006-3363. PMID   12748128.
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