Physiology, Female Reproduction


Article Author:
Julie Rosner
Tijana Samardzic


Article Editor:
Manbeer Sarao


Editors In Chief:
David Wood
Andrew Wilt
Hajira Basit


Managing Editors:
Avais Raja
Orawan Chaigasame
Khalid Alsayouri
Kyle Blair
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Abbey Smiley
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beenish Sohail
Hajira Basit
Phillip Hynes
Sandeep Sekhon


Updated:
7/24/2019 6:21:43 PM

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 a mature fetus and become ready for delivery. A female’s reproductive years are those 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 at 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 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
      • 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 contain 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.[6] 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, the 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.[7]
      • 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 columnar epithelium. The lining of the inside of the cervical canal is the endocervix, composed of stratified squamous 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][10][11][12]
    • Vulva 
      • The vulva describes the external female genitalia: labia majora, labia minora, clitoris, vulvar vestibule, urethrethral meatus, vaginal orifice.[12] 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.[10] Bartholin’s glands open lateral to the vaginal opening.[12]

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 take place, 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 continued growth of a select number of follicles. 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 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]


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Physiology, Female Reproduction - Questions

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What are the four anatomical segments of a fallopian tube?



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Assuming a 28-day menstrual cycle, which of the following hormones would be the most concentrated in serum on day 20 of the cycle?



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A 15-year-old female presents complaining of intense lower abdominal pain for the last year. Upon further questioning, you find out she has not reached menarche. She has three sisters, all of whom began menstruating at age 13 and have no medical conditions. She is 5 ft 6 in tall and weighs 51kg. She has never been sexually active. Physical exam reveals fully developed breasts as well as dark axillary and pubic hair. External genitals are normal. Which of the following suggests that this patient does not have androgen insensitivity syndrome?



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A 17-year-old female is at the 3rd percentile for height and has a known aortic murmur. She comes to her healthcare practitioner to discuss amenorrhea. Which of the following is most likely to be found in this patient?



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A 28-year-old G3P0 female is brought to the emergency department after vomiting at work. She had been experiencing nausea and vomiting every morning for the past two weeks. Her last menstrual period was six weeks ago. She denies recently eating out, travel, or sick contacts. On physical exam, her mucous membranes are dry, and her eyes are sunken. Her pregnancy test is positive. The hormone that denotes the positive pregnancy test is responsible for which of the following actions?



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Physiology, Female Reproduction - References

References

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Machaty Z,Miller AR,Zhang L, Egg Activation at Fertilization. Advances in experimental medicine and biology. 2017     [PubMed]
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Adams JM,Taylor AE,Schoenfeld DA,Crowley WF Jr,Hall JE, The midcycle gonadotropin surge in normal women occurs in the face of an unchanging gonadotropin-releasing hormone pulse frequency. The Journal of clinical endocrinology and metabolism. 1994 Sep     [PubMed]
Taylor AE,Whitney H,Hall JE,Martin K,Crowley WF Jr, Midcycle levels of sex steroids are sufficient to recreate the follicle-stimulating hormone but not the luteinizing hormone midcycle surge: evidence for the contribution of other ovarian factors to the surge in normal women. The Journal of clinical endocrinology and metabolism. 1995 May     [PubMed]
Stocco C,Telleria C,Gibori G, The molecular control of corpus luteum formation, function, and regression. Endocrine reviews. 2007 Feb     [PubMed]
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Foti PV,Ognibene N,Spadola S,Caltabiano R,Farina R,Palmucci S,Milone P,Ettorre GC, Non-neoplastic diseases of the fallopian tube: MR imaging with emphasis on diffusion-weighted imaging. Insights into imaging. 2016 Jun     [PubMed]
de Ziegler D,Pirtea P,Galliano D,Cicinelli E,Meldrum D, Optimal uterine anatomy and physiology necessary for normal implantation and placentation. Fertility and sterility. 2016 Apr     [PubMed]
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