• Dr.
Mariam Al-Awadhi
The            • Department of Physiology
               • Faculty of Medicine
Reproductive   • Maryam.awathi@ku.edu.kw
System         • 3rd floor, room 334a
               • Lecture ID 30, 31, 32
Objectives
• To understand the function of the reproductive system
• The know the function of different organs and glands of the male and female reproductive systems
• To describe the process gametogenesis (spermatogenesis and oogenesis)
• To describe the hormonal control of the male and female reproductive system (hypothalamus-pituitary-
  gonadal axis)
• Explain the menstrual cycles
• To describe the process of fertilization and acrosomal reaction
• To understand the stages of pre-embryonic development
• To know the hormones of pregnancy
• To understand male and female contraceptive methods
• To understand infertility and the assisted reproductive methods
                                                                                                         2
Sexual
Reproduction
               3
Functions of the Reproductive System
1. Production of gametes: sperm within testes and eggs within ovaries.
2. Storing and transporting gametes.
3. Fertilization of egg and growth of zygote takes place in female reproductive system.
4. Production of sex hormones.
                                                                                          4
Reproduction
• humans at birth are sexually immature.
• Humans undergo a sequence of events until puberty, during which a child becomes a
  sexually competent young adult.
• Sexual maturity typically occurs between the ages of 9 - 14 in girls and 11 - 16 in boys.
                                                                                              5
Male
Reproductive
System
               6
                                  Mariam Al-Awadi- Human Reproduction -2019
  Vas
                                                                              Bulbourethral gland
Organ          Function
Testes         Primary sex organ the produce sperms and sex hormones
Epididymis     Sites of maturation (ability to swim and gain resistance against pH
               and temperature) and some storage of sperm
Vas deferens   Conduct and store sperm
Urethra        Conducts sperm (and urine)
                                                                                                    7
Penis          Organ of copulation
    The Testes
• Testes are main organs in male reproductive system.
•   Develop inside abdominal cavity but descend into scrotal sac during
    last 2 months of fetal development.
•   Suspended in scortum (important to regulate testicular temperature).
•   Undescendent testes (sterility and cancer).
                                                                           8
     The Testes (cont.)
•   Testes consist of lobules containing:
1. Seminiferous tubules:
    Contains cells required for spermatogenesis:
     ➢ Germinal cells: sperms
     ➢ Sertoli cells: possess follicle stimulating hormone
        (FSH) receptors; they support, nourish and
        regulate spermatogenic cells
2. Interstitial tissue:
    ➢ Leydig cells: They are located in   the spaces
       between tubules. They possess luteinizing
       hormone (LH) receptors ➔ testosterone                 9
Spermatogenesis
                  10
Spermatogenesis (cont.)
• Starts at ~11-16 years of age
• Occurs in the seminiferous tubules upon LH & FSH
 stimulation
• Takes on average 74 days to complete
• 120 million sperm are produced/day
 (~ 60 - 150 million/day)
                                                     11
       Spermatogenesis (cont.)
•      Spermiogenesis:
     • The last step in spermatogenesis. It results in     Spermatogenesis
       transformation of spermatids to sperms.
                                                         Spermiogenesis
    • Mediated by Sertoli cells that are responsible
      for eliminating most of the spermatid
      cytoplasm to give spermatozoa.
                                                                     12
Sperm (spermatozoa) contain 3 parts:
1. Head: contains a nucleus covered by an acrosome (a specialized lysosome that stores
   enzymes to penetrate egg).
1. Middle piece: contains mitochondria wrapped around microtubules of the flagellum
   (mitochondria provide energy for movement).
2. Tail: contains microtubules as components of flagellum; its movements propels sperm.
                                                                                          13
Control of Male
Sex Hormone
Secretion
Hypothalamic-pituitary-
      testes axis
                                                    Androgen-binding
                          Phagocytosis                  proteins
                                         Luminal fluid
                                                                       14
At the completion of spermatogenesis:
• Spermatozoa will be released into the lumen of seminiferous tubules (non motile), but they move
 by bulk movement of fluid secretion.
• In the epididymis, sperms become mature
 and gain motility. Sperms also become more
 resistance to change in pH and temperature.
• Most of the sperms are then stored in the
 vas deferens.
                                                                                                    15
                                                 Mariam Al-Awadi- Human Reproduction -2019
           Vas
Gland                  Function
Seminal vesicles       60% of the semen; thick viscous fluid containing nutrients (fructose) for use by sperm.
                       Contains prostaglandins that stimulate smooth muscle contraction along male and
                       female reproductive system
Prostate gland         30% of the semen; secretes alkaline secretion that increase motility of sperm
                       Prostatic hypertrophy and prostate cancer
Bulbourethral glands   Produce clear viscous secretion known as pre-ejaculate that clear the urethra from
                       urine residues                                                             16
                                                                                                     17
                                               Mariam Al-Awadi- Human Reproduction -2019
• During ejaculation, the vas deferens (contains sperms) obtains fluid secretions of seminal vesicle
  and prostate, and together with the sperms the semen is carried by the ejaculatory duct to the
  urethra.
• Semen (seminal fluid) is a thick whitish fluid that contains sperm (5%) and glandular secretions.
                                                                                                      16
Penis
• Male organ for sexual intercourse
• Three columns of spongy erectile tissue with extensive blood space extend
  through the shaft.
• It has a shaft and enlarged tip called gland penis, which is covered by layer
  called foreskin. In circumcision the foreskin is removed.
• Circumcised males are 25-35% less likely acquire certain sex transmitted
  diseases (eg AIDS).
• It also decreases the incidence of penile cancer and urinary track infection.
                                                                                  18
 Erection
• Stimuli (physical, psychological, visual)
  trigger brain to send nerve signals through
  spinal cord autonomic nerves →
  relaxation of arterial smooth muscle (by
  release of nitric oxide “NO”) → fill the
  erectile tissue with blood → compress
  compression of veins → penile erection.
• During erection bladder sphincter closes
  off so no urine enters the urethra.
                                                19
    Erection (cont.)
•   An erection lasts for a limited time and the penis generally returns to a flaccid state following
    ejaculation.
• Erectile dysfunction (impotency):
    ➢ inability to achieve or maintain erection
    ➢Its prevalence is estimated to be 26% under the age of 40
    ➢ Cause by number of factors ie, poor blood flow, some medications, and illnesses
    ➢ Management: treat the underlying cause.
                                                                                                        20
  Ejaculation
 1. The first phase of ejaculation is emission:
      Sexual stimuli trigger brain → send nerve signals through spinal cord to the muscular wall of:
      • Epididymis, vas deferens to empty sperm.
      • Reproductive glands (seminal vesicles, prostate, and bulbourethral glands) to release secretion.
      resulting in movement of sperm from the vas deference to the urethra.
2. The second phase of ejaculation is expulsion:
    It is the movement of sperm from the urethra to the exterior
    • Gland secretions stimulate rhythmical contractions of muscles at the base of the penis and within the
      urethral wall expel the semen in spurts.
    • During ejaculation, urinary bladder sphincter closes, so that no semen can enter the bladder.
                                                                                                           21
  Ejaculation
Ejaculation results in the expulsion of semen (achieved at the peak of sexual arousal):
    •   2-5 ml of semen that contains ~300 million sperms
    •   Life of sperm in female genital tract is ~ 24 - 72 hrs
    •   ~100- 200 reach the egg
    •   Only one sperm enters an egg
                                                                                          22
                            • It is the main sex hormone in males.
Functions of                • Important for development and function of male reproductive
                              glands and organs.
Testosterone                • Essential for the maturation of sperm.
                            • Essential for development of male secondary sex characteristics:
                                • Oil and sweat glands secretion leading to acne and body odor
                                • Enlargement of larynx and vocal cords; deepening of voice
                                • Development of hair on face, chest and back
                                • Tallness, longer legs, broad shoulders
   Male pattern hair loss
                                • Greater muscle strength (athletes, anabolic steroids)
                                • Sex drive and aggressiveness
                                • Triggers baldness if appropriate genes are present
                                                                                      23
Female
Reproductive
System
               24
Female Reproductive System
Organ                        Function
Ovaries                      Primary sex organ that produce egg each month and sex hormones.
Oviducts (fallopian tubes)   Conduct egg; site of fertilization.
Uterus (womb)                Houses developing embryo and fetus. Consists of endometrium,
                             myometrium perimetrium. Cervical cancer.
Vagina                       Receives penis during copulation, serves as birth canal and exit for
                             menstrual flow.                                                    25
Oogenesis
• Mitosis of primary oogonia occurs during fetal life until midgestation (peak of 7 million oocytes) and
 then ceases.
• Primary oocyte begins first meiotic division in utero: meiosis I is arrested in prophase until the time of
 ovulation.
         Fetal life           Puberty – before ovulation                      Fertilization
    Arrest in meiosis I            Arrest in meiosis II                 Completion of Meiosis II
    Ovarian Reserve
                                                                                                           26
Oogenesis (cont.)
• Then there is progressive loss of oocytes & by puberty there are approximately 400,000 oocytes (only
 ~400 follicles ovulate in women).
• At the time of ovulation, the primary oocyte completes the first meiotic division producing the first polar
 body and a secondary oocyte. It arrests in metaphase of 2nd meiotic division.
           Fetal life           Puberty – before ovulation                       Fertilization
      Arrest in meiosis I            Arrest in meiosis II                Completion of Meiosis II
     Ovarian Reserve
                                                                                                                27
Oogenesis (cont.)
 • Sperm penetration (fertilization) causes completion of 2nd meiotic division and the expulsion of a
  second polar body.
           Fetal life          Puberty – before ovulation                Fertilization
       Arrest in meiosis I         Arrest in meiosis II              Completion of Meiosis II
       Ovarian Reserve
                                                                                                        28
29
         Ovarian Cycle
                                                                 primary
                                                                                           Meiosis I → Meiosis II
      FSH dependent                            Lasts for years
                                                                 70-85 days       48 hrs
    1. Follicular Phase
                                                                               2. Ovulation
                                                                                                                    LH dependent
                                                                              3. Luteal Phase
• Follicles are made up of the oocyte, and follicular cells.
• Follicular cells differentiate to granulosa and thecal cells that produce female sex hormones and fluid.
• Changes in the ovary are the result of changing levels of FSH and LH from the anterior pituitary.                                30
                                                                                                                                        28
         Control of Ovarian Steroidogenesis
                                                            CNS
                                                                            (   -   )
Hypothalamic-pituitary-ovarian axis                    Hypothalamus
                                              GnRH             GnRH
                                                                                -
                                                     FSH               LH
                                                      Anterior Pituitary
                                      Granulosa                                 Thecal cell
                                         cell
                                                                                              31
            ❖ Ovarian cycle:
               • Follicular phase.
               • Ovulation.
Menstrual      • Luteal phase.
Cycle       ❖ Endometrial cycle:
               • Proliferative phase.
               • Secretory phase.
               • Menstruation.
                                        32
                                                    Mariam Al-Awadi- Human Reproduction -2019
                                                                          Ovulation
                               Anterior Pituitary
• 28 day vs longer cycles
• Peak E, LH, ovulation
• Trophic hormones
• Functional, basal layers
• Body temperature increase.
                                                                                                33
                                                                                                     31
                                                            Ovulation
            3. Hypothalamus GnRH
                   secretion
                                                  7. E positive feedback on LH
                                                  → LH surge → ovulation
                                                                             9. High P, E and inhibin → -ve feedback on FSH
                                                                             and less on LH
                  4. Pituitary secretion of FSH                              8. LH stimulate CL
                                                                                                         11. CL regression
                                                                             produces E, P & inhibin
                                                                                                                         1. CL dies, E & P levels fall
            5. FSH recruit     follicles
            which secrete E.
                                                                     10. P → uterine gland development
                               6. E → endometrial growth
2. Menses                                                                                                                                34
                • 1. Follicular Phase
                 • Lasts from day 1 to about day 13 of the cycle (assuming that
                   the cycle is 28 days) during which:
                     • FSH ➔ growth and maturation of follicles (only ONE will
                       become mature).
Ovarian cycle        • Granulosa and thecal cells secrete estradiol (peaks at ~
                       day 12; 2 days before ovulation).
                     • Granulosa cells are stimulated by FSH; thecal cells are
                       stimulated by LH.
                 • The rapid increase in estradiol secretion ➔ positive
                   feedback effect ➔ rapid LH secretion ➔ LH SURGE.
                                                                          35
                2. Ovulation: A woman usually ovulates only one ovum a month.
                • LH SURGE:
                    • Completion of meiosis I.
                    • Rupture Graafian follicle wall (day 14) ➔ OVULATION ➔
                       expulsion of secondary oocyte (with the 1st polar body) out of
Ovarian cycle          the ovaries into fallopian tube.
                • If ova is fertilized by a sperm ➔ ova completes the second
                   meiotic division ➔ formation of 2nd polar body.
(cont.)
                • 3. Luteal Phase
                • After ovulation ➔ LH stimulates empty follicle (corpus luteum) to
                  secrete estradiol & progesterone (and inhibin which inhibits FSH
                  only) ➔ negative feedback inhibition of FSH and LH ➔ prevents
                  the development of a new follicle
                • Regression of corpus luteum (life span 14±2) ➔ decrease in
                  estrogen and progesterone ➔ MENSTRUATION.
                                                                           36
               1. Proliferative Phase
                    • Occurs during ovarian follicular phase.
                    • An increase in estradiol stimulates the growth (proliferation)
                      of stratum functionale of the endometrium.
              2. Secretory Phase
                    • Occurs during ovarian luteal phase.
Endometrial         • An increase in progesterone ➔ stimulates development of
                      uterine glands.
                    • Effects of increased estradiol and progesterone levels:
Cycle                   • endometrium becomes thick, vascular and spongy in
                          appearance.
                        • The uterine glands become engorged with glycogen,
                          lipids & proteins.
                        • endometrium ready to accept and nourish an embryo.
               3. Menstruation
                   • Resulting from a decrease in estradiol and progesterone
                     levels during late luteal phase.
                                                                           37
    Menstruation
• Process of menstruation:
    -       Arteries that supply the lining of uterus restrict and capillaries are weakened.
    - Damaged vessels detach layers of uterine lining: blood, mucus, and degenerative tissue descend from
      uterus.
•   Menarche: first menstrual period, usually starts at 11-14 years.
• Amenorrhea: menarche did not occur by age of 16, or uterine cycle was
  interrupted for more than 6 months without pregnancy.
        -    Causes: non-functional ovaries, developmental abnormalities, weight loss or
             excessive exercise.
• Menopause is cessation of menstrual cycle because ovaries are no more
  functioning. Occurs between 45-55 years.                                                        38
                                            Mariam Al-Awadi- Human Reproduction -2019
Functions of Estrogen & Progesterone
 • Estrogen is essential for normal development and function of female reproductive organs
   (ovaries, uterus.. etc).
 • Estrogen is responsible for development and maintenance of female secondary sexual
   characteristics:
     • Less body and facial hair.
     • More fat beneath the skin to give a rounded appearance.
     • Enlargement of pelvic girdle and cavity to give wider hips.
 • Both estrogen and progesterone:
    • Required for breast development.
    • Help maintain endometrium during pregnancy.
    • Help suppress gonadotropin (LH and FSH) secretion.
    • Inhibit prolactin secretion.
                                                                                             39
                • The main function of male and female reproductive
Fertilization     system is to produce gametes.
and Pregnancy   • Fertilization is the union of sperm and egg to form a
                  zygote, the first cell of new individual.
                                                                          40
    Fertilization
•   During the act of sexual intercourse, the male ejaculates ~ 300 million sperms into the female
    vagina and ONLY ~100-200 sperms survive to enter fallopian tube. Remain viable up to 3 days.
• When does fertilization occur?
  • Ovulated oocyte in the fallopian tube lasts12~
     24 hrs following ovulation.
     •   It occurs if intercourse takes place within 3-5
         days prior to the day of ovulation.
                                                                                                     41
  Acrosomal Reaction
• Several sperms penetrate corona
  radiata. and attempt to penetrate
• Sperms binding to zona pellucida
  (glycoprotein layer surrounding the
  oocyte) → acrosome burst → release of
  digestive enzymes → sperms
  penetration of zona pellucida reaching
  the oocyte cell membrane
• Sperm plasma membrane fuse with
  oocyte membrane and sperm nucleus
  enters the cytoplasm
                                           42
    Acrosomal Reaction (cont.)
• When sperm nucleus enter oocyte:
  ➢ Cortical granules fuse with cell membrane
    and release their content → formation of
    fertilization envelope that prevent other
    sperms from entering the oocyte (prevent
    polyspermy).
  ➢ The zona pellucida is now called the
    fertilization envelope.
  ➢ Completion of meiosis II
                                                43
Process of
Development
• 1. Cleavage:
•   Mitotic division of zygote.
• 2. Growth:
•   Increase in size of the divided cells.
• 3. Morphogenesis:
•   Shaping of the embryo through cell
migration.
• 4. Differentiation:
•   Cells take specific structure and function.
                                                  44
Process of Development
         1              2   3
    •   Embryonic Period:
        The period of system formation(organogenesis).
    •   Fetal Period:
        Growth and development.
                                                         45
Pre-embryonic
Development
• Cleavage:
• Occurs as the zygote goes down the fallopian tube giving
 a morula.
• First cleavage division is completed ~ 30 hrs after
 fertilization.
• Zygote divides by mitosis to double the number of cells
 (2 cells, 4 cells, 8 cells, etc).
• The zygote reaches morula stage after 3-4 days (enters
 uterus).
                                                             46
Pre-embryonic
Development (cont.)
• Blastocyte:
•    Early embryonic structure, consists of:
    • An inner cell mass:
      • develops into fetus and some extraembryonic
         membrane (amnion that secretes amniotic
         fluid).
    • Chorion (trophoblast cells):
      • will become part of placenta.
                                                      47
  Pre-embryonic
  Development (cont.)
• Implantation:
  • Trophoblast cells of blastocyst attach to uterine wall (5-6
    days).
  • Blastocyst implantation in the endometrium starts on 6th
    day and completes by 10th-12th day.
  • Blastocyst secreted enzymes that invades the uterine
    endometrium and endometrial grows around the
    blastocyst until it is completely engulfed.
  • Hormone human chorionic gonadotrophin (hCG) is now
    secreted from implanted blastocyst.
                                                                  48
     Pregnancy
     Hormones
• Human chorionic gonadotropin (hCG):
  • Secreted from trophoblast cells of the implanted blastocyst.
  • Becomes   detectable in the mother's blood and urine between 6 and
   14 days after fertilization
   (3 - 4 weeks gestational age) - pregnancy test.
  • Causes corpus luteum viability and hormonal secretion until placenta
   takes over ~ 3-4 months of gestation (luteal-placental shift).
• Estrogen and progesterone:
  • Important to support the endometrium.
  • Inhibit the contraction of uterine muscle.                             49
                                                                                49
                                            Mariam Al-Awadi- Human Reproduction -2019
      Male vs. Female Reproductive Systems
        Male Reproductive System                                 Female Reproductive System
• Gonads (testes) resides outside of the              • Gonads (ovaries) resides in the abdominal
  abdominal cavity.                                     cavity.
• Release of gametes (sperm) is                      • Release of gamete (egg) occurs once per
  continuous.                                          month.
• Gametic reserve is replenished through out
  life.                                               • Gametic reserve is limited in number.
• Testosterone exhibits negative feedback on          • Estrogen exerts both negative and positive
  LH and FSH.                                           feedback on LH and FSH.
                                                      • Activity of female tract is rhythmic monthly or
• Activity of male tract does not show rhythm.
                                                        on the length of pregnancy.
• Male tract serves only sperm transport,             • Female tract serves sperm and egg transport,
  store and maturation.                                 store, maturation, fertilization, placentation,
                                                        gestation and delivery.
                                                                                                          50
                • Barrier method: condom (failure rate 2% - 12%).
Male            • Coitus interruptus: withdrawal of penis before ejaculation
Contraception     (failure rate 20% - 30%).
                • Vasectomy: surgical procedure where the
                  Vas deferens are tied or disconnected
                  (failure rate 0%).
                                                                          51
    Female
    Contraception
• Contraceptive pill:
    Combination of synthetic estrogens & progestins causes negative feedback on GnRH & therefore
    ovulation doesn’t occur (false luteal phase; failure rate < 1%).
•     Female diaphragm:
    Similar to male condom (barrier method, failure rate 20%).
• Intrauterine device (IUD):
    Also known as the loop; failure rate < 2%.
                                                                   52
                                                                                               52
Female
Contraception (cont.)
• Temperature method: (BETTER FOR FERTILIZATION)
 Temperature on day of ovulation increases by ~0.5˚C (due to
 progesterone secretion, failure rate 4%).
• Rhythm method:                                                 53
 Avoid intercourse near the time of ovulation; menstrual cycle
 must be regular; (failure rate 20% - 30%).
•Sterilization/ tubal ligation:
Fallopian tubes are ligated (failure rate 0%).
                                                                      53
Infertility
• Failure of couples to achieve pregnancy after couple of years.
• Estimated prevalence is 15% of couples are infertile.
• Causes are evenly distributed between males and females:
    • Males the main cause is low sperm count and/or large proportion of abnormal sperm, caused
      by environmental influence.
    • Females the main cause is overweight.
• Treatment:
    • Underlying cause.
    • Female fertility drug that stimulate ovulation.
    • Assisted reproductive technologies.
                                                                                             54
            Assisted Reproductive Technologies
 • Artificial insemination by donor
      • Sperm is placed in the vagina by a physician.
      • Good if the partner has low sperm count because the sperm can be collected
        over time and concentrated so that sperm count is sufficient for fertilization.
                              • In vitro Fertilization (IVF)
                                   • Administration of fertility drug to immature egg in the lab → mature egg.
                                   • Concentrated sperm is incubated with the egg in the lab.
                                   • Embryos are transferred to the uterus.
• Gamete Intrafallopian Transfer (GIFT)
    • Eggs are removed and reintroduced at the same time in fallopian tube along with sperm.
    • Performed only if fallopian tubes are intact and sperms are normal.
                                                                                                                 55