Introduction to Organismal Biology (BIOL221) - Dr. S.G. Saupe; Biology Department, College of St. Benedict/St. John's University, Collegeville, MN 56321; ssaupe@csbsju.edu; http://www.employees.csbsju.edu/ssaupe/

Human Reproduction

I. Female anatomy/physiology

A.  Female form & function - "eyeglass gal"

B. Ovary - the key organ of reproduction. The ovary has two main functions:

1. Egg (oocyte) production
    Ovum is another term for egg. The ovum develops in a follicle. The follicle is lined with special cells (granulosa cells). All the ova that a female will ever possess are present at birth (i.e., they are as old as she is).  In fact, the maximum number is achieved before birth and continues to decrease through her lifetime (Table 1).

    Each month following puberty, one follicle enlarges and releases an egg (ovulation). The egg is swept into the oviduct by finger-like extensions. When the follicle collapses it becomes the corpus luteum.

2. Hormone production
    The ovary produces progesterone and estrogen.

C.  Oogenesis - egg production
    Diploid cells (oogonium) in the ovary begin meiosis. Oogonia divide mitotically to produce primary oocytes.  These begin meiosis but stop in prophase of the first meiotic division.  Once a month a primary oocyte in the follicle enlarges and continues the meiotic process.  During this process, the first meiotic division is completed, which produces a secondary oocyte and polar body (which disintegrates).  The secondary oocyte is released from the ovary on ovulation but doesn't complete the second meiotic division until stimulated by fertilization. 

D. Menstrual Cycle
    On average the menstrual cycle lasts 28 days (some longer, some shorter). In a perfect 28-day cycle, Day 1 is the first day of bleeding; Day 14 is ovulation. The cycle can be divided into two phases:

• Pre-ovulatory  or Follicular Phase :  Day 1 → Day 14
• Post-ovulatory or Luteal Phase:  Day 14 → day 28

E. Hormonal Control
    There is a complex regulatory control over the cycle. Involves various hormones and body parts. The basic scheme is:

Brain (hypothalamus) → gonadotropal releasing hormone (GnRH) → anterior pituitary → follicle stimulating hormone (FSH) and luteinizing hormone (LH) → ovary → stimulates growth of a follicle → which produces estrogen → estrogen levels increase (days 1 –14) → estrogen on day 14 causes "feedback" to the anterior pituitary stimulating a large production of LH ("LH surge"; by the way, ovulation prediction kits test for LH) → LH surge stimulates ovulation → follicle collapses, becomes corpus luteum → corpus luteum produces progesterone → shuts off hypothalamus → no FSH or LH production by anterior pituitary → no developing follicles/ova during the luteal phase (waiting to see if there is a 'bun in the oven') → if no pregnancy by day 28 corpus luteum disintegrates → no progesterone → hypothalamus turns on → FSH/LH production →cycle repeats.

F. Uterine Changes
    Estrogen stimulates growth of new cells in the endometrium (lining) during days 1 - 14 of the cycle.  As a result, the first half of the cycle can also be considered the Proliferative phase. Progesterone stimulates glands in lining to secrete mucous and other materials and is required for the maintenance of the endometrium. This is the Secretory Phase; Day 14 → 28. Thus, estrogen is like a "fertilizer" and progesterone is like a "stabilizer" to maintain the lining.

G. If No Pregnancy
    If there is no pregnancy, by day 28 the corpus luteum disintegrates, progesterone production stops, the lining flows off (menstruation).

H. If Pregnancy Occurs
    The egg is viable for about 24 hours. It moves into the oviduct where fertilization occurs (about day 14). From day 14 to day 21 the zygote/embryo travels to the uterus where it implants (day 21). The zygote cells divide during the travels and form a blastula. The chorion (part of the embryo) produces chorionic gonadotropin (hCG) that stimulates the corpus luteum to continue to produce hormones to maintain the uterine lining that must persist throughout pregnancy. Eventually the corpus luteum stops producing progesterone, etc. - but fortunately, the hormones are supplemented by those produced by the placenta.

Note: (1) continued progesterone production by the corpus luteum or placenta means that there will be no FSH or LH → no ovulation → no further eggs will be released until the "one in the oven if done"; and (2) hCG (human chorionic gonadotropin) is the marker used in pregnancy test kits.

I. Puberty
    Sexual maturity is initiated when the level of melatonin, produced by the pineal gland, drops.  Melatonin inhibits the hypothalamus from producing GnRH. Thus, until the levels decline, there can be no ovulation.

J. Menopause
    The ovaries stop responding to FSH and LH = no estrogen → no ovulation → no periods

II. Male anatomy/physiology

A. Testis - key organ of reproduction in males. The testes have two main functions:

1. Sperm production
    Requires low temperature, therefore a scrotal sac. Warm temperatures results in decreased and abnormal sperm production (consider boxers vs. briefs). Occurs in the seminiferous tubules (another example of the importance of S/V ratios). Sperm production is a continuous process once puberty is reached. FSH stimulates spermatogenesis. FSH acts on Sertoli cells – provide nourishment and chemical signals to the sperm - sperm nursemaids.  The Sertoli cells that produce androgen binding protein that binds testosterone to keep it in the testis.  

2. Hormone production
    Produces testosterone. Produced by interstitial cells (Leydig cells) in the testes. LH stimulates testosterone production.

B.  Spermatogenesis
    Spermatogonial cell (2n) divides mitotically to produce lots of primary spermatocytes (2n) which can undergo meiosis I to produce secondary spermatocytes (n).  These  complete meiosis II to form spermatids which look nothing like mature sperm.  They require a maturation period during which they take on the final form of the sperm.  The production of sperm is something like a factory conveyor belt system.  As the cells proceed through meiosis and maturation they are ultimately released into the duct in the seminiferous tubules

B. Hormonal regulation

hypothalamus → GnRH → pituitary gland → FSH and LH (also called Interstitial Cell Stimulating Hormone, ICSH) → the LH stimulates interstitial cells to produce testosterone → the testosterone and FSH (working via the Sertoli cells) in combination stimulate spermatogonial cells to produce sperm.  Sperm production is constant following puberty. It is not cyclic as in females.

C. Other structures of the male reproductive tract

• Prostate – produces an alkaline fluid that helps neutralize the acidity of the vagina;
• Bulbourethral gland (Cowper's gland) – secretes a mucous that helps lubricate the urethra and penis;
• Seminal vesicles – produce fructose (sperm food) and prostaglandins (cause the uterus to contract to help propel sperm on their journey);
• Vas deferens – tube in which sperm will mature while waiting to be shipped out of the body;
• Epididymus – sperm maturation;
• Semen – the mixed secretions from the prostate, bulbourethral gland and seminal vesicles plus the sperm.

III. Fertilization
    As stated above, fertilization occurs on about day 14. Of the many sperms released (in a typical male, there are 100 million sperm mL^-1 x 3 mL semen = 300 million sperm per ejaculation.  As an aside, if there are less than 20 million sperm mL^-1 a male is considered to be functionally sterile), relatively few sperm ever make it to the egg. Reasons for the failure of sperm to make it to the egg include:

1. defective sperm
2. hostile environment in the vagina – sperm often swim in dense packs (like hungry dogs). This may be a way to protect the inner ones.
3. female immune system attacks some
4. they swim up the wrong oviduct (how many males do you know who ask for directions?)
5. some get stuck in the oviduct
6. don't find mucin – secreted by the cervix; liquid during ovulation; easy to swim in; provides a "channel" or perhaps a road into the uterus.

    The sperm require contact with the female reproductive tract to become "capacitated" – capable of fertilizing the egg. Once at the egg, the sperm race to be the first to enter. They release digestive enzymes from the acrosome (pointed head region) to begin digesting the outer covering. The entry of a sperm stimulates the formation of the zona pellucida, a shell-like structure, around the egg. This prevents any additional sperm from penetrating. As the fertilized egg moves toward the uterus for implantation, cilia along the way release enzymes to digest the zona pellucida. If the zona pellucida is still intact, the embryo can't implant in the uterus. As a side note – this can be a minor problem for in vitro fertilization – the zona must be removed before the fertilized egg is reimplanted in the mother.

IV. Preventing Fertilization

A. Natural Family Planning
    Determine time of ovulation and plan intercourse accordingly (remember that safe/fertile periods must account for egg (24 h) and sperm (24-48 h) viability and irregularities of the cycle. To determine the time of ovulation a woman can:

1. monitor the consistency of the cervical mucous – it changes consistency at ovulation and becomes watery (vs. sticky);
2. count days – in a regular cycle, ovulation typically occurs halfway;
3. monitor her basal body temperature – during the follicular phase it is about 97.5 F but increases to about 98.3.

B. Barrier Methods
    These methods provide a barrier that prevents the sperm from leaving the vagina and entering the uterus. These include condom, foam, diaphragm, cervical cap (like a smaller more permanent diaphragm), sponge, suppository; all can be used +/- spermicide. Each method has it’s advantages and disadvantages. One additional benefit of the condom is that is reduces the spread of sexually-transmitted diseases.

C. Hormonal Methods
    These methods supply hormones, usually progesterone or analog that disrupts the normal menstrual by "tricking the body into thinking it is pregnant". These include:

1. Oral contraceptives (the "Pill") - Contains progestin (progesterone, prevents FSH & LH release) and synthetic estrogens; body "thinks" it is in the luteal phase (pregnant), therefore no ovulation. On 20 days, off 5.
2. Norplant. - Capsule implanted in the arm, releases progestin, inhibits ovulation up to 5 years.
3. Depo-Provera – injected, progestin, lasts about 3 months.

D. Douche
    cleanse sperm from vagina; very low success rate

E. Intra-uterine device
    No longer popular because it can cause pelvic inflammatory disease. Camel herders knew that a stone in the uterus of a camel would prevent her from becoming pregnant (how did they figure that out?). Anyway, presumably these uterine implants irritate the lining of the uterus and prevent fertilized egg implantation.

F. Sterilization Methods
    Vasectomy and tubal ligation.

G. Withdrawal
     Coitus interruptus; very low success rate

H. Ru486
    The "morning after pill". Blocks progesterone receptors/production; uterine lining and implanted egg sloughs off.

V. Preventing Contraception – the future?

A. Anti-pregnancy vaccine
    Tested in chimps/baboons. Stimulates production of antibodies against hCG, which is required to maintain the uterine lining. Therefore, no hCG, no corpus luteum, no lining maintained, no pregnancy.

B. Male Birth Control Pill

• Testosterone - large dose would cause the pituitary gland to slow release of FSH and LH, therefore, less sperm production.  About 97% effective (but side effects like acne, weight gain, lower levels of HDL - cholesterol, and increased risk of prostate cancer)
• Lonidamine and derivatives - these chemicals prevent sperm from staying attached to the lining of the seminiferous tubules meaning that they are prematurely released before they've had a chance to mature/develop into a sperm.
• Gossypol, from cotton seed. Inhibits sperm production, may not be reversible. 
• Sperms were recently shown to have a protein required for calcium uptake into the tail occurs in no other body cell.  If this protein is defective calcium uptake is blocked and the sperm is infertile.  This raises the possibility of creating an antibody to this protein to immobilize it.  (Travis, J.  Sperm protein may lead to male pill.  Science News, Oct 13, 2001)

C.  Immunotherapy against GnRH - this would prevent FSH & LH production and hence sperm formation.

D.  Note – there is currently interest in developing male contraceptives but, in general, there are comparatively few for males, possibly because: (1) the physiology of reproduction; female reproduction is designed to be turned on/off; (2) gender bias of scientists; and (3) must turn off millions of sperm vs. one egg.

VI. Reproductive Technologies (improving fertility)

• Artificial Insemination
• Freezing Sperm
• Freezing Embryos
• In vitro fertilization (test tube baby)
• Surrogate motherhood.
• Choosing sex of baby
• Intra-fallopian transfer – insert eggs & sperm, or zygote directly into fallopian tube (oviduct) to increase success rate over in vitro fertilization techniques.

VII. Miracle of Life
    Check out the excellent video, Nova - Miracle of Life, available in the library. It includes remarkable footage of the entire reproductive process from start (intercourse) to finish (baby).