Physiology, Uterus


Introduction

The uterus, also known as the womb, is a female reproductive organ that is responsible for many functions in the processes of implantation, gestation, menstruation, and labor.

Anatomic Overview

The uterus is a thick-walled muscular structure that lies in the midline of the abdominal pelvic cavity. It contains three layers: the endometrium (innermost layer), myometrium, and the perimetrium (outermost layer). The endometrium’s thickness and structure vary based on hormonal stimulation

The uterus has four parts: the fundus, corpus, isthmus, and cervix. The corpus is the largest segment and connects to the cervix via the isthmus. The cervix connects the uterine body to the vaginal lumen. The uterus sits posterior to the bladder and anterior to the rectum.[1][2]

Uterus Support Structure

The round ligament connects the uterus to the abdominal wall and includes the artery of Sampson. The broad ligament connects the lateral portion of the uterus with the fallopian tube and ovary. The uterine artery, cardinal arteries, and ureter travel within the broad ligament. The ovarian ligament connects the ovary to the lateral surface of the uterus. The infundibulopelvic (IP) ligament connects the ovary to the abdominal wall. Within the IP ligament are the ovarian artery and vein. 

Uterine Vasculature

The uterine artery is the main blood supply to the uterus, with some collateral supply from the ovarian artery.

Uterine Innervation

The uterus is innervated sympathetically and parasympathetically through the hypogastric nerve and pelvic splanchnic nerves, respectively.[3][4][5]

Development

At 5 to 6 weeks gestation, the paramesonephric (Mullerian) ducts arise as coelomic epithelial invaginations that appear on the lateral surface of the paired urogenital ridges, the development of these ducts is due to the absence of anti-Mullerian hormone.[6][7] At eight weeks gestation, the paramesonephric ducts fuse vertically. The fused cranial and horizontal ends will give rise to what will ultimately become the fallopian tubes, while the caudal component will fuse to form the uterus, cervix, and upper third of the vagina. The uterine corpus remains underdeveloped at birth and reaches functional and anatomical maturity at the time of menarche.[8][9][10]

Function

The uterus carries out many functions:

  • Implantation site of the blastocyst
  • Provides protection and support for the fetus to grow
  • Site of menstruation

Mechanism

Reproductive Cycle 

In the female reproductive cycle, there are two concurrent cycles, the ovarian cycle, and the uterine (menstrual) cycle. The ovarian cycle consists of a series of events that occur during and following oocyte maturation. The uterine cycle consists of a series of changes within the endometrium in preparation for the arrival of a fertilized ovum that will develop within the endometrium until birth.

The reproductive cycle can subdivide into the menstrual phase, preovulatory phase, ovulation, and postovulatory phase. The function of the uterus in each of these phases follows:

In the menstrual phase, a decline in estrogen and progesterone levels stimulates the release of prostaglandins, which results in vasoconstriction of arterioles within the uterus. The vasoconstriction eventually leads to hypoperfusion of these cells, which results in cell death. This process initiates the sloughing off of blood, fluid, and epithelial cells from the endometrial walls into the cervix and out through the vagina.

In the preovulatory phase, estrogen is released into the blood, which repairs the endometrium. The endometrium undergoes other changes and doubles in thickness.

During ovulation, the follicle ruptures and releases an oocyte which enters the uterine tube.

In the postovulatory phase, progesterone and estrogen stimulate further growth of endometrial glands and thickening of the endometrium in preparation for the implantation of a fertilized ovum. If fertilization does not occur, progesterone end estrogen levels decline, and the menstruation stage occurs.

If the egg becomes fertilized, the zygote is propelled down the fallopian tubes into the uterus. The zygote cells divide rapidly during this descent. The cells of the zygote continue to divide until it becomes a blastocyst. This blastocyst implants by invading the wall of the endometrium.[11]

Pregnancy 

When the blastocyst successfully implants into the endometrial lining, it develops over many weeks into an embryo and then a fetus. During the development of an embryo into a fetus, changes occur within the endometrium that leads to placental formation. The placenta provides a crossing point between the developing fetus and maternal circulation. In pregnancy, the uterus hypertrophies to accommodate for the growing fetus. It typically reaches the height of the umbilicus at 20 weeks and the xiphoid process at 38 weeks.

Labor

The uterus undergoes many changes during labor due to the release of various hormones. Nearing the seventh month of pregnancy, progesterone levels begin to decline while estrogen levels steadily rise. The increasing ratio of estrogen to progesterone causes the myometrium to become more sensitive to stimuli that promote contractions. Additionally, fetal cortisol rises in the eighth month of pregnancy, which further reduces progesterone’s effects.[12][13]

As true labor approaches, oxytocin and prostaglandins both play a role in further stimulating myometrial contractions and increasing contractile strength. The fetus causes the myometrium and cervix to stretch, which also stimulates uterine contractions.[14]

During true labor, the release of oxytocin and prostaglandins stimulate a positive feedback loop which continues to increase uterine contractile strength. These uterine contractions dilate and efface the cervix. Again a positive feedback loop begins where the effacement and dilation of the cervix further promote uterine contractions. Contractions become more frequent and longer in duration as labor progresses. The next stage of labor begins when the fetal head enters the birth canal and completes when the infant is born. The myometrium continues to contract after birth, causing the placenta to shear from the back of the uterine wall for delivery through the birth canal.[15]

Pathophysiology

Within uterine development, Mullerian duct abnormalities can be present. These can include incomplete fusion of the Mullerian ducts during embryogenesis, leading to abnormal uterine development. There are also a host of acquired uterine conditions that can occur in any of the three uterine layers but most commonly target the endometrium and myometrium. In acquired or congenital uterine abnormalities, patients can either appear symptomatic or have associated complications such as infertility, recurrent miscarriages, and prematurity. Appropriate application of the function and common pathologies of the uterus can directly impact the mortality and morbidity of women everywhere, especially as it relates to pregnancy-related changes. A discussion of the most common pathologies in each of these categories will appear below.

Clinical Significance

Congenital Defects

The septate uterus is the most common structural uterine anomaly.[16] It occurs when the partition between the two fused Mullerian ducts fail to resorb. This remnant results in a fibromuscular septum that can be partial or complete, which would divide the uterine cavity and cervix into two separate components.[17] Uterus didelphys occurs when there is a complete failure of fusion of the paired Mullerian ducts. As such, the uterus presents as a paired organ with two endometrial cavities, each with a cervix.[18] Additionally, a bicornuate uterus is a structural anomaly that can occur. In this condition, there is an incomplete fusion of the paramesonephric ducts, which produces a bicornuate uterus. Similar to uterus didelphys, there are two separate endometrial cavities; however, there is one cervix.[18]

Acquired Conditions

One of the most common diseases of the uterus is uterine fibroids, also known as leiomyomata. This disorder characteristically presents with benign, smooth muscle tumors found in the myometrial layer [18]. Another condition that affects the myometrium is adenomyosis. In this disease, endometrial tissue embeds into the myometrium, which can result in abnormal uterine bleeding and secondary dysmenorrhea.[19]

A common pathology affecting the endometrium is endometriosis. This condition is an estrogen-dependent disorder characterized by glandular tissue and stroma outside the uterine cavity.[20] It can often be accompanied by dyspareunia, bleeding, dysmenorrhea, and infertility.[21] Endometrial polyps are another common pathology that causes benign, local overgrowths of endometrial tissue.[21] Endometritis, an inflammatory disorder of the endometrium, is due to a bacterial infection either from external bacteria such as Chlamydia trachomatis or from the normal bacterial flora found in the vagina.[22] Another condition that can affect the endometrium is endometrial hyperplasia, which is caused by excessive growth of endometrial glands due to increased unopposed exposure to estrogen and can be a predisposing factor for endometrial carcinoma.[23]

Endometrial carcinoma is a common gynecological malignancy and the most common type of uterine cancer. Its characteristics include malignant cells arising in the endometrial layer. It classifies into two major types: Type I and Type II and can present with abnormal uterine bleeding, including post-menopausal bleeding.[24][25]


Article Details

Article Author

Adi Gasner

Article Editor:

Aatsha P A

Updated:

5/9/2021 11:37:30 AM

PubMed Link:

Physiology, Uterus

References

[1]

Roach MK,Andreotti RF, The Normal Female Pelvis. Clinical obstetrics and gynecology. 2017 Mar     [PubMed PMID: 28005593]

[2]

Cooke PS,Spencer TE,Bartol FF,Hayashi K, Uterine glands: development, function and experimental model systems. Molecular human reproduction. 2013 Sep     [PubMed PMID: 23619340]

[3]

Kido A,Togashi K, Uterine anatomy and function on cine magnetic resonance imaging. Reproductive medicine and biology. 2016 Oct     [PubMed PMID: 29259437]

[4]

Ameer MA,Fagan SE,Sosa-Stanley JN,Peterson DC, Anatomy, Abdomen and Pelvis, Uterus StatPearls. 2021 Jan     [PubMed PMID: 29262069]

[5]

Rosner J,Samardzic T,Sarao MS, Physiology, Female Reproduction StatPearls. 2021 Jan     [PubMed PMID: 30725817]

[6]

Moncada-Madrazo M,Rodríguez Valero C, Embryology, Uterus StatPearls. 2021 Jan     [PubMed PMID: 31613528]

[7]

Cunha GR,Kurita T,Cao M,Shen J,Cooke PS,Robboy SJ,Baskin LS, Tissue interactions and estrogenic response during human female fetal reproductive tract development. Differentiation; research in biological diversity. 2018 May - Jun     [PubMed PMID: 29684808]

[8]

Sulak O,Cosar F,Malas MA,Cankara N,Cetin E,Tagil SM, Anatomical development of the fetal uterus. Early human development. 2007 Jun;     [PubMed PMID: 17045762]

[9]

Ye L,Mayberry R,Lo CY,Britt KL,Stanley EG,Elefanty AG,Gargett CE, Generation of human female reproductive tract epithelium from human embryonic stem cells. PloS one. 2011     [PubMed PMID: 21698266]

[10]

Cunha GR,Robboy SJ,Kurita T,Isaacson D,Shen J,Cao M,Baskin LS, Development of the human female reproductive tract. Differentiation; research in biological diversity. 2018 Sep - Oct     [PubMed PMID: 30236463]

[11]

Kapila V,Chaudhry K, Physiology, Placenta StatPearls. 2021 Jan     [PubMed PMID: 30855916]

[12]

Chwalisz K,Garfield RE, Regulation of the uterus and cervix during pregnancy and labor. Role of progesterone and nitric oxide. Annals of the New York Academy of Sciences. 1997 Sep 26;     [PubMed PMID: 9329845]

[13]

Olson DM,Mijovic JE,Sadowsky DW, Control of human parturition. Seminars in perinatology. 1995 Feb     [PubMed PMID: 7754411]

[14]

Hutchison J,Mahdy H,Hutchison J, Stages of Labor 2020 Jan;     [PubMed PMID: 31335010]

[15]

Gross MM, [The five stages of labour]. Zeitschrift fur Geburtshilfe und Neonatologie. 2002 Nov-Dec     [PubMed PMID: 12476398]

[16]

Raga F,Bauset C,Remohi J,Bonilla-Musoles F,Simón C,Pellicer A, Reproductive impact of congenital Müllerian anomalies. Human reproduction (Oxford, England). 1997 Oct     [PubMed PMID: 9402295]

[17]

Taylor E,Gomel V, The uterus and fertility. Fertility and sterility. 2008 Jan     [PubMed PMID: 18155200]

[18]

Patton PE, Anatomic uterine defects. Clinical obstetrics and gynecology. 1994 Sep     [PubMed PMID: 7955655]

[19]

Pavlik RM, Adenomyosis--an ignored uterine disease. The Nurse practitioner. 1995 Apr;     [PubMed PMID: 7596529]

[20]

Lim HJ,Wang H, Uterine disorders and pregnancy complications: insights from mouse models. The Journal of clinical investigation. 2010 Apr     [PubMed PMID: 20364098]

[21]

Cakmak H,Taylor HS, Implantation failure: molecular mechanisms and clinical treatment. Human reproduction update. 2011 Mar-Apr;     [PubMed PMID: 20729534]

[22]

Kitaya K,Takeuchi T,Mizuta S,Matsubayashi H,Ishikawa T, Endometritis: new time, new concepts. Fertility and sterility. 2018 Aug     [PubMed PMID: 29960704]

[23]

Reed SD,Newton KM,Clinton WL,Epplein M,Garcia R,Allison K,Voigt LF,Weiss NS, Incidence of endometrial hyperplasia. American journal of obstetrics and gynecology. 2009 Jun     [PubMed PMID: 19393600]

[24]

Sorosky JI, Endometrial cancer. Obstetrics and gynecology. 2012 Aug     [PubMed PMID: 22825101]

[25]

Di Cristofano A,Ellenson LH, Endometrial carcinoma. Annual review of pathology. 2007     [PubMed PMID: 18039093]