Introduction

The reproductive system in females is responsible for producing gametes (called eggs or ova), certain sex hormones, and maintaining fertilized eggs as they develop into mature fetuses and become ready for delivery. A female’s reproductive years are between menarche (the first menstrual cycle) and menopause (cessation of menses for 12 consecutive months). During this period, cyclical expulsion of ova from the ovary occurs, with the potential to become fertilized by male gametes (sperm). This cyclic expulsion of eggs is a normal part of the menstrual cycle.

Development

Female gametes derive from germ cells. In utero, oogonia rapidly divide until approximately 7 million germ cells form by the 7th month of gestation. The number of germ cells then rapidly declines; most oogonia perish while the remaining cells, primary oocytes, begin the first meiotic division. These cells arrest in prophase I and remain dormant as such until menarche.[1][2][3][4] A primordial follicle made up of granulosa and theca cells surrounds each oocyte. When primordial follicles mature, the granulosa cells proliferate to form concentric layers around the oocyte. The oocyte itself undergoes a drastic volume increase. With the onset of menarche, finite groups of oocytes periodically resume meiosis and continue to develop. At the time of fertilization, oocytes are arrested in metaphase II. The oocyte becomes an ovum as it expels its second polar body, and meiosis resumes when the egg undergoes activation by a sperm cell (a male gamete).[1][2][3][4]

Organ Systems Involved

Female Reproductive Organs

Ovaries

• The ovaries are female gonads, the site of gametogenesis and the secretion of sex hormones. The outer cortex of each ovary is the site of follicular development, while the inner medulla of each contains blood vessels and connective tissue.[5]

Fallopian Tubes

• The vulva describes the external female genitalia: labia majora, labia minora, clitoris, vulvar vestibule, urethral meatus, and vaginal orifice.[6] The labia majora are lateral to the labia minora, fusing anteriorly to make up the mons pubis (a layer overlying the pubic symphysis). The vulvar vestibule is the area medial to the labia minora and is the location of the urethra and vaginal openings.[7] Bartholin’s glands open lateral to the vaginal opening.[6]
• The vagina is a flexible, fibromuscular tubular structure extending from the vulvar vestibule to the uterine cervix. The distal vagina is the introitus. The anterior vagina abuts the posterior bladder wall, while the posterior vagina abuts the anterior rectum.[8][9][7][10][6]
• The uterus consists of the corpus (body) and cervix. The superior aspect of the uterine corpus is the fundus, while the inferior portion adjacent to the cervix is called the isthmus/lower uterine segment. The uterine walls contain three distinct layers: the endometrium, myometrium, and the serosa. The endometrium lines the uterine cavity; its thickness and structure vary with hormonal stimulation. The myometrium consists of smooth muscle fibers and is the middle and thickest layer of the uterine wall. The serosa is the outermost lining of the uterus.[11]
• The uterine cervix is a tubular structure contiguous with the uterine cavity and the vagina, acting as a conduit between the two. The inferior cervix opens into the upper vagina at the cervical os. The lining of the cervix that protrudes into the vagina is called the ectocervix and consists of stratified squamous epithelium. The lining of the inside of the cervical canal is the endocervix, composed of columnar epithelium. The region where the ecto- and endocervix meet, characterized by the transformation from columnar to squamous epithelium, is the transformation zone. The transformation zone is the most frequent location for cervical dysplasia and malignant transformation.
• Fallopian tubes provide a passageway for oocytes to travel from the ovaries into the uterine cavity. The part of each tube closest to the ovary contains fimbria: finger-like projections that help move the expelled oocyte further into the tube—the fimbria transition into the ampulla, the part of the tube with the widest lumen. The ampulla becomes the isthmus as the lumen narrows and projects towards the uterus. The tube then passes into the uterus, where it becomes the interstitial portion.[12] This opening is where the traveling oocyte exits the tube and enters the uterine cavity. 

Uterus

• The uterus consists of the corpus (body) and cervix. The superior aspect of the uterine corpus is the fundus, while the inferior portion adjacent to the cervix is called the isthmus/lower uterine segment. The uterine walls contain three distinct layers: the endometrium, myometrium, and the serosa. The endometrium lines the uterine cavity; its thickness and structure vary with hormonal stimulation. The myometrium consists of smooth muscle fibers and is the middle and thickest layer of the uterine wall. The serosa is the outermost lining of the uterus.[11]
• The uterine cervix is a tubular structure contiguous with the uterine cavity and the vagina, acting as a conduit between the two. The inferior cervix opens into the upper vagina at the cervical os. The lining of the cervix that protrudes into the vagina is called the ectocervix and consists of stratified squamous epithelium. The lining of the inside of the cervical canal is the endocervix, composed of columnar epithelium. The region where the ecto- and endocervix meet, characterized by the transformation from columnar to squamous epithelium, is the transformation zone. The transformation zone is the most frequent location for cervical dysplasia and malignant transformation.

Vagina

• The vagina is a flexible, fibromuscular tubular structure extending from the vulvar vestibule to the uterine cervix. The distal vagina is the introitus. The anterior vagina abuts the posterior bladder wall, while the posterior vagina abuts the anterior rectum.[8][9][7][10][6]

Vulva 

• The vulva describes the external female genitalia: labia majora, labia minora, clitoris, vulvar vestibule, urethral meatus, and vaginal orifice.[6] The labia majora are lateral to the labia minora, fusing anteriorly to make up the mons pubis (a layer overlying the pubic symphysis). The vulvar vestibule is the area medial to the labia minora and is the location of the urethra and vaginal openings.[7] Bartholin’s glands open lateral to the vaginal opening.[6]

Function

Menarche is a female’s first menstrual cycle, marked by her first episode of menstrual bleeding. Menarche occurs during puberty, preceded by breast growth, axillary and pubic hair growth, and a growth spurt. At the initiation of each menstrual cycle, a number of primordial follicles in the female’s ovaries continue development. One becomes the dominant follicle and continues to grow while the other follicles become atretic and cease to develop. The dominant follicle develops into a Graafian follicle, at which point meiosis I has completed, and the ovum is no longer in prophase I arrest.[1][2][3][4] At ovulation, the Graafian follicle expels the ovum from its surrounding tissue, henceforth called the corpus luteum. If no fertilization takes place, the expulsion of the egg occurs from the uterus along with the secretory endometrial lining under the influence of declining levels of progesterone; this presents as menstrual bleeding. If fertilization does occur, the fertilized egg implants in the endometrial wall and the endometrial lining is maintained by progesterone secreted (initially) by the corpus luteum until the placenta takes over.[1][2]][4]

Mechanism

The normal menstrual cycle divides into the follicular and luteal phases, with ovulation occurring between phases. The follicular phase begins with menstrual bleeding and ends right before the LH (luteinizing hormone) surge. The luteal phase begins with the LH surge and ends with the onset of menses. A typical cycle lasts approximately 28 days; the luteal phase lasts 14 days, while the follicular phase is more variable in its time course. 

Low serum levels of estradiol and progesterone mark the beginning of the follicular phase. The lack of inhibitory feedback allows for an increase in pulsatile GnRH (gonadotropin-releasing hormone) levels, leading to elevations in FSH (follicular stimulating hormone) and LH.[13][14][15] This rise in FSH levels stimulates follicular maturation, resulting in a select number of follicles' continued growth. The growth of these follicles results in increasing FSH and estradiol levels. By the end of the follicular phase, the dominant follicle has emerged and increased to a size of approximately 20-25mm. The increase in estradiol induces thickening of the endometrium to accommodate the potential implantation of a fertilized egg.

When estradiol levels reach a critical level, the negative feedback effect of estradiol on LH becomes a positive feedback effect, resulting in a massive surge in LH concentration (and a smaller surge in FSH levels.)[13][15][16] Approximately 36 hours following the LH surge, the oocyte is released from the dominant follicle and travels into the uterus via the fallopian tube.[14] The corpus luteum (the remaining follicular tissue following oocyte expulsion) releases progesterone, inhibiting the release of LH and FSH and stimulating the formation of the secretory endometrium.[14][17] In the absence of fertilization, declining LH levels contribute to a decline in progesterone and estradiol levels.[15][16] In the presence of fertilization, the oocyte implants into the endometrium and releases chorionic gonadotropin, which maintains the corpus luteum and, thus, progesterone production.[13][15]

Clinical Significance

The clinical relevance of female reproductive physiology comes to bear for clinical issues ranging from adolescent entry into child-bearing years, pregnancy, infertility issues, and menopause.