Female Reproductive System

• Male sex hormones


  • Testosterone (T)
  • Dihydrotestosterone (DHT)
  • Estrogen (E2)

  
• Spermatogenesis and male sex hormone production


  1. Hypothalamus and pituitary

  2. GnRH

  3. Follicle stimulating hormone (FSH)

  4. Luteinizing hormone (LH)

  5. LH stimulates Leydig cells to make testosterone (T)

  6. FSH stimulates Sertoli cells to convert testosterone to dihydrotestosterone (DHT) and estradiol (E2)

  7. T and DHT are essential for spermatogenesis

  
• Two-Cell, Two-Gonadotropin Mechanism


  Spermatogenesis and meiosis in males

  
• Spermatogenesis in males


  1. Spermatogonium, a type of stem cell, continuously divides to make primary spermatocytes

  2. During meiosis, a single primary spermatocyte makes four spermatids that become spermatozoa

  
• Oogenesis and meiosis in females


  1. Oogenesis and oocyte meiosis in the female begins during fetal life but all oocytes arrest development in the first meiotic division (meiosis I) as primary oocytes

  2. Oocyte meiosis does not continue until ovulation which only occurs at puberty

  3. Unlike spermatogenesis in males, no new germ cells develop after fetal life

  4. A single primary oocyte becomes only one mature oocyte rather than four such as during spermatogenesis in males

  
• Oogenesis


  • The final number of oocytes is established during fetal life in mammals
  • Oocytes then begin to die (atresia) before the female is born and the trend continues until menopause
  • At puberty, typically one oocyte (or more depending on species) will ovulate each cycle

  
• Oogenesis, Ovulation and Pregnancy


  1. Gonadotropin releasing hormone (GnRH)

  2. Follicle stimulating hormone (FSH)

  3. Luteinizing hormone (LH)

  4. Other factors: Photoperiod or season, Presence of opposite sex/pheromones, Social interactions, Genetics and Stress

  
• Factors that activate neurons controlling GnRH neurons in hypothalamus


  Increase GnRH secretion into HH blood portal system

  
• Anterior pituitary gonadotrope cells


  Increase FSH and LH secretion in response to GnRH
• Follicle Growth and Ovulation


  1. FSH promotes ovary follicle growth

  2. LH promotes follicle growth and ovulation in females

  3. Oocytes are arrested in meiosis I (primary oocytes) in a primordial follicle

  4. An oocytes is selected to continue development and the follicle with oocyte grows in response to FSH

  5. Fluid accumulates in the follicle and it forms an antrum (antral follicle)

  6. LH and FSH stimulate the growing follicle to produce estradiol (E)

  7. Ovulation is stimulated by LH. The follicle ruptures and the oocyte is released into the oviduct

  8. The follicle tissue then forms a corpus luteum (CL). LH stimulates the CL to produce progesterone

  
• Follicle Growth and Ovulation


  • At puberty, follicle growth is continuous with follicles at nearly all stages in the ovary at one time, however, ovulation of a large antral follicle and formation of the CL only occurs once a cycle after puberty
  • Multiparous species such as pigs, dogs, cats and mice will ovulate multiple large follicles from both ovaries

  
• Ovulation and Formation of the Corpus Luteum (CL)


  1. Ovulation: rupture of follicle and release of oocyte and fluid into oviduct

  2. Occurs spontaneously during the reproductive cycle in most mammals

  3. Triggered by large concentration of follicle estradiol (E2) that stimulate large concentrations "surges" of GnRH from hypothalamus and LH from pituitary

  4. In some animals, the act of copulation/mating triggers surges of GnRH and LH and ovulation
• Types of female reproductive cycles in mammals


  • Estrous cycle
  • Menstrual cycle
• Estrous cycle


  • Reproductive cycle in non-primate mammals
  • Day 0 or beginning of cycle designated by signs of female sexual receptivity (estrus or heat)
  • Polyestrus: Animals that have repeated cycles throughout the year
  • Seasonal polyestrus: Repeated cycles during Fall or Spring
  • Monoestrus: One or two cycles a year
  • Anestrus: Animal that has stopped cycling
• Menstrual cycle


  • Essentially same processes as estrous cycle with these exceptions:
  • Uterine endometrium grows considerably and is sluffed off at the end of the cycle if pregnancy doesn't occur. Results in menstruation or bleeding
  • Some animals with menstrual cycles do not display sexual receptivity at time of ovulation
  • Day 0 designated by signs of menstruation, NOT sexual receptivity and ovulation like estrous cycle. Ovulation occurs near Day 14 of the menstrual cycle (between menstruations)

  
• The Male and Female HPG Axis


  1. GnRH neurons are found in two hypothalamic nuclei: Arcuate nucleus (ARC) and preoptic area (POA)

  2. ARC and POA neurons in males secrete GnRH into HH blood portal system in tonic (continuous, low amplitude) pulses

  3. ARC neurons in females secrete GnRH into portal system in tonic, low amplitude pulses but the POA in the female is sexually dimorphic and can release surge pulses of GnRH (high frequency, high amplitude) and is called the surge center

  4. Follicular phase: Tonic release of GnRH stimulates FSH and LH secretion from the anterior pituitary and FSH stimulates a group of follicles to grow. This process is called recruitment
• Menstrual cycle


  Cycles do not display sexual receptivity at time of ovulation
• Day 0


  Designated by signs of menstruation, NOT sexual receptivity and ovulation like estrous cycle
• Ovulation


  Occurs near Day 14 of the menstrual cycle (between menstruations)
• Hypothalamic nuclei with GnRH neurons


  • Arcuate nucleus (ARC)
  • Preoptic area (POA)
• ARC and POA neurons in males


  Secrete GnRH into HH blood portal system in tonic (continuous, low amplitude) pulses
• ARC neurons in females

  Secrete GnRH into portal system in tonic, low amplitude pulses (like the male)
• POA in the female


  Is sexually dimorphic and can release surge pulses of GnRH (high frequency, high amplitude) and is called the surge center
• Follicular phase


  1. Tonic release of GnRH stimulates FSH and LH secretion from the anterior pituitary

  2. FSH stimulates a group of follicles to grow (recruitment)

  3. Smaller antral follicles will die (atresia) but one large follicle will continue to grow and ovulate (dominant follicle)

  4. FSH and LH, particularly LH, stimulate the large follicle to produce large concentrations of E2

  5. Large concentration of E2 have positive feedback on the female GnRH surge center (POA)

  6. Surges of GnRH cause surges of LH that ultimately cause ovulation
• LH


  Stimulates follicle Theca cells to produce testosterone (T)

  
• FSH


  Stimulates follicle Granulosa cells to convert T into E2
• Physiological effects of E2


  • Effects female brain, stimulating sexual receptivity in some animals
  • Causes production of vaginal/cervical mucus for copulation and sperm transport
  • Stimulates smooth muscle contraction in reproductive tract for oocyte/sperm transport
• Signs of estrus


  • Lordosis: Curvature of spine into the mating posture
  • Increased animal activity and standing to be mounted
  • Increased reproductive tract blood flow and swelling
• Luteal phase


  1. Follicle theca and granulosa cells differentiate into luteal cells

  2. Theca cells become small luteal cells and granulosa, large luteal cells

  3. Blood vessels grow within the tissue and the corpus luteum (CL) forms

  4. LH stimulates Luteal cells in the CL to produce progesterone (P4)

  5. Progesterone prepares the female for pregnancy and internal development of young

  6. P4 has strong negative feedback on the surge center and ovulation does not occur during the luteal phase
• Corpus luteum (CL)


  Forms after ovulation from the follicle
• Physiological effects of progesterone


  • Prepare female for gestation and internal development of young
  • Stimulates uterine glands to secrete substances that support the embryo
  • Cervix constricts and secretes thick mucus to act as a barrier
  • Stimulates mammary gland growth
  • Inhibits uterine smooth muscle contractions
  • Inhibits negative immune responses toward embryo
  • Has negative feedback on surge center
• Progesterone


  Has strong negative feedback on GnRH surge center and can block or inhibit ovulation
• Reproductive technologies using progesterone


  • Intrauterine device (IUD) in humans
  • Controlled Internal Drug Release (CIDR) in cattle and sheep
• Luteolysis


  1. Without signals from the embryo, the CL degrades and a new cycle begins

  2. If pregnancy does not occur, the uterus or ovary, depending on species, will produce a "luteolytic" factor that causes the CL to degrade and disappear from the ovary

  3. The luteolytic factor is prostaglandin F2 alpha (PGF2⍺)

  4. Menstruation in primates is caused by a reduction in P4 following luteolysis

  5. During the follicular phase in primates, follicle E2 promotes endometrial cell proliferation

  6. During the luteal phase, CL P4 promotes endometrial cell maintenance and secretion

  7. A decrease in P4 leads to vasoconstriction of endometrial arteries, reduced blood flow results in cell/tissue necrosis (death), sluffing and menstruation
• Fertilization


  1. Occurs in the oviduct

  2. When a sperm cell meets the oocyte, proteins on the sperm cell plasma membrane bind receptors on the zona pellucida (outer layer or "shell") of oocyte

  3. The sperm enters the oocyte cytoplasm and outer layer becomes impermeable to additional sperm

  4. Within an hour, sperm and egg nuclei (pro-nuclei) fuse to form a nucleus and zygote (diploid single celled embryo)

  5. Conceptus: Refers to embryo and early placental tissue

  6. First mitotic cell division within 24-48 h

  7. Inner cell mass (becomes fetus)

  8. Trophectoderm (becomes placenta)

  9. The early conceptus eventually migrates into the uterus and begins to hatch from the zona pellucida

  10. Paracrine communication between the conceptus and the endometrium is important to maintain pregnancy

  11. The cow conceptus secretes interferon tau (IFNT) to signal its presence and disrupt luteolysis

  
• Maternal Recognition of Pregnancy (MRP)


  The conceptus of many mammal species will release a factor that signals it presence and disrupts luteolysis

  
• MRP factors


  • Humans: Human Chorionic Gonadotropin (hCG)
  • Cattle: Interferon tau (IFNT)
  • Pigs: Estrogens and Prostaglandins
  • Horses: Unknown