Revision notes OCR A2 F224 module 2 part 1

Human reproductive systems

Female reproductive organs: produce female gametes (oocytes) in the ovaries; the site of fertilisation in the fallopian tubes and fetal development in the uterus; production of the female sex hormones – oestrogen and progesterone.

The breasts contain mammary glands which produce milk.

The male reproductive organs: produce male gametes (sperm); produce the male sex hormone (testosterone); introduce sperm into the female for fertilisation.

The ovaries

Contain many primary follicles. The follicles in an ovary are in different stages of development and maturity.

The Testes

They lie outside the male body in a scrotal sac – this provides a lower than normal body temperature for optimum sperm production. Each testis is made of many seminiferous tubules; sperm production begins at puberty. The Epididymis stores the newly produced sperm.

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Gametogenesis

Oogenesis is the production of egg cells. It begins during the development of the female fetus

Germinal epithelium cells divide by mitosis to form oogonia

1. Growth occurs and cell division by meiosis – this is only to prophase 1.

2. The primary oocyte is formed; this is surrounded by the primary follicle. It is diploid (2n)

3. From puberty, some oocytes continue on from prophase 1 to the end of the first division of meiosis.

4. The two daughter cells are haploid (n).

5. One daughter cell produces the secondary oocyte, the other (smaller) forms the polar body

6. Of the six to twelve follicles that develop, one becomes dominant. This is the Graafian follicle, (the rest stop developing).

7. The secondary oocyte continues to develop, stopping at metaphase 2 of meoisis.

8. The secondary oocyte is released at ovulation; it is haploid and is surrounded by the zona pellucida and corona radiate.

9. If sperm cells are present, a sperm nucleus will enter the oocyte and meiosis 2 takes place. A second polar body is also formed (these degenerate).

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Spermatogenesis

Production of sperm is called spermatogenesis. It occurs in the seminiferous tubules. These are lined inside with diploid spermatogenia. These divide by mitosis and grow into primary spermatocytes. The first meiotic division results in secondary spermatocytes. The second meiotic division produces haploid spermatids. These will grow and differentiate into sperm cells supported by the Sertoli cells (nurse cells).

Sertoli cells nourish all spermatogenic cells; remove degenerating spermatogenic cells by phagocytosis; control the release of spermatozoa into the lumen of the tubule; secrete the hormone inhibin which is a feedback inhibitor of gonadotrophin release; secrete androgen-binding protein which concentrates testosterone in the seminiferous tubules where it promotes spermatogenesis; removes excess cytoplasm as spermatids develop into spermatozoa.

The sperm cell consists of a head with haploid nucleus and an acrosome tip of hydrolytic enzymes.

A mid piece containing many mitochondria and a tail consisting of contractile filaments and microtubules (you must add the detail about the tail, tail will not get the marks!)

Remember the sperm requires mitochondria to provide energy in the form of ATP to allow the tail to beat for swimming.

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You may be asked to sequence the process of spermatogenesis or oogenesis or compare and contrast the two processes.

spermatogenesis oogenesis

occurs in testes occurs in ovary ;

onset at puberty onset before birth ;

continuous monthly / cyclic ;

four gametes (per germ cell) one gamete / egg / ovum (per germ cell) ;

fully differentiated at endof process

not fully differentiated ;

mature sperm produced /division completed

secondary oocyte produced / divisiondivision not completed / completed atfertilisation ;

no polar bodies / equaldivisions

polar bodies / unequal divisions ;

millions / large numbersproduced

only one, at a time / per month / fixed number;

involves ICSH / testosterone involves FSH / oestrogen and progesterone ;

accessory cells / Sertoli cells follicle cells ;

production, throughout life production ceases at menopause / 45-60 ;

Gametogenesis is controlled by hormones from the hypothalamus and anterior lobe of the pituitary gland. These hormones then stimulate the ovaries or testes to produce hormones.

The hormones involved in Gametogenesis

• Both sexes are controlled by release of hormones from the hypothalamus and anterior pituitary gland.

• Hypothalamus releases a hormone – gonadotrophin releasing hormone (GnRH) into the blood.

• Anterior pituitary gland is stimulated to secrete FSH and LH. These act on the ovaries and testes, triggering the development of follicles and sperm.

Male hormones

• FSH – stimulates sperm development

• LH – stimulates the interstitial cells between the seminiferous tubules of the testis to produce testosterone, (therefore LH hormone is often called interstitial cell stimulating hormone (ICSH).

• Testosterone – first produced in the fetus, controls the development of the male reproductive organs. Increases at puberty, causes enlargement of the reproductive organs and the development of the secondary sex characteristics.

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Key phrase to use when explaining the action of hormones – NEGATIVE FEEDBACK

• Level of testosterone increases, it reaches a certain concentration and inhibits the hypothalamus from stimulating the pituitary gland.

• ICSH stops being produced.

• Testosterone production stops until its level falls below that needed to inhibit the hypothalamus.

The cycle then begins again – it keeps testosterone levels relatively constant

Hormones of the menstrual cycle

• Reproduction in females involves 2 linked cycles.

• Ovarian cycle

• Uterine cycle

• As both are regulated by the same hormones the release of the oocyte can be synchronised with the development of the uterine lining.

Hormones of the menstrual cycle

Hormone Producing organ Effect

Gonadotrophin Hypothalamus stimulates anterior pituitary to produce two hormones

FSH

Anterior pituitary

Binds to follicle cells and stimulates follicle to mature and produce oestrogen

LH stimulates ovulation and development of corpus luteum

Oestrogen Mature follicle cells Rising levels inhibit FSH and initially LH followed by LH surge. Causes endometrium to begin thickening

Progesterone Corpus luteum Rising levels inhibit FSH and stimulate Secretory phase of endometrium development.

The hormone sequence:

FSH OESTROGEN LH PROGESTERONE

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• Progesterone inhibits the production of FSH, in turn production of other hormones stop (including progesterone). This means the inhibition of FSH stops and oestrogen production starts again.

The phases

• Proliferative phase – the lining of the uterus (endometrium) regenerates

• Ovulation phase – oocyte released from the mature follicle into the oviduct

• Secretory phase – endometrium secretes nutrients in preparation for implantation

• Menstrual phase – where the lining of the uterus is shed

Fertilisation

Fertilisation may result if a sperm is released into the female reproductive tract to meet a secondary oocyte in the fallopian tube.

1. Secondary oocyte – swept by feathery fimbriae into the fallopian tube; then moved along by peristalsis and by cilia that line it.

2. Sperm needs to reach oocyte before it travels too far down the oviduct.

3. Once at the oocyte, the capacitated sperm binds to a glycoprotein receptor on the zona pellucida. The acrosome reaction is triggered, (Capacitation is the process of sperm maturation (or activation) that occurs post-ejaculation. Without capacitation sperm have a reduced capacity to fertilize the egg. There are several identifiable changes that occur both on the surface and within the spermatozoa.

4. One sperm penetrates the outer layer of cells surrounding the egg; it passes through the zona pellucida. The sperm head reaches the plasma membrane of the oocyte; here it binds to another receptor.

5. Lysosomes in the oocyte (cortical granules), fuse with the zona pellucida and change the proteins. This is a cortical reaction – a fertilisation membrane is formed which prevents the entry of any further sperm.

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6. The haploid male nucleus stimulates the oocyte to complete meiosis and divide (the second cell produced becomes a polar body)

7. The male nucleus enters and fuses with the oocyte nucleus.

8. A diploid zygote is formed. The diploid chromosome number is restored. Chromosomes of each pair are from two different parents, therefore there will be new combinations of alleles

9. Rapid mitosis occurs. The zygote turns into a bundle of cells called a blastocyst. This continues to travel down the oviduct towards the uterus. Implantation occurs approximately 7 days later.

The journey of the blastocyst

Blastocyst – bundle of cells – can only implant if the endometrium is at the correct stage in the menstrual cycle (approx 20th day). Implantation starts when blastocyst makes contact with endometrium – inflammation like reaction.

Trophoblast - endometrium to grow out around blastocyst, this will go on to form the placenta. Blastocyst now becomes embryo.

Blastocyst starts to secrete hormone “HCG” HUMAN CHORIONIC GONADOTROPHIN”, continues for up to 8 weeks. Stimulates corpus luteum to carry on producing progesterone. This will inhibit release of FSH for duration of pregnancy = no more follicles ripening.

Trophoblast continues to develop. Chorion, one of membranes surrounding embryo develops projections, these grow into endometrium. These projections (villi) are called chorionic villi. They form the functional unit of exchange in placenta. Allow blood systems of mom and baby to come very close but never mix.

Hormones in pregnancy

Hormones from the blastocyst are produced as soon as it is implanted. They control the maintenance of the fetus, the birth and lactation.

During pregnancy

HCG stimulates the corpus luteum to maintain the pregnancy and the lining of the uterus by secretion of progesterone and oestrogen.

Human placental lactogen stimulates the breast tissue to be receptive to oestrogen and progesterone.

Oestrogen and progesterone maintain the pregnancy and stimulate the breast tissue to develop.

Prolactin stimulates the growth of mammary glands and prepares for milk production

Oxytocin stimulates the uterus to contract and starts the birth process

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During birth

Oxytocin stimulates contractions and allows birth to process. This is an example of positive feedback control – as the contractions develop more oxytocin is released.

During lactation

Prolactin promotes and maintains milk production and inhibits ovulation, it increases as oestrogen and progesterone levels fall.

Oxytocin acts as the releaser hormone as the baby suckles and stimulates the muscular contractions around the milk glands that allow the release of milk

Typical questions – graph interpretation / explanations on the effect of the hormones

Contraception - Two strategies used to prevent pregnancy

Method 1 – prevents fertilisation

The pill

Condoms / femidoms

Diaphragm

Injections and implants

Sterilisation

Method 2 – prevents implantation of the blastocyst

Intrauterine device (IUD)

Morning- after pill

Control mechanism Biological effect Ethical consideration

Birth control pill

Combination of synthetic oestrogen and progesterone, creates artificial negative feedback and prevents ovulation

Increased risk of thrombosis and breast cancer - increasing the load on medical facilities and society

Condoms / diaphragm / femidom Acts as a barrier to prevent sperm from meeting egg

Reduce the risk of sexually transmitted disease, but may be unacceptable from religious viewpoints

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Injections and implants, e.g. Norplant and DMPA (Depo-Provera)

Contraceptive hormones, given subcutaneously, last up to 3 years

Offer no protection from STDs, carry increased risk of thrombosis and breast cancer which affects society and medical facilities

IUD Prevents implantation of embryo either physically or by presence of copper

May cause uncomfortable uterine pains and excess bleeding may be considered unethical since the embryo is already formed

The morning-after pill Used if contraceptive device fails or if not used. Large doses of steroids prevents implantation

Removes responsibility and may be considered unethical. Causes extreme stomach pains and sickness.

Natural rhythm method Intercourse during ovulation avoided

None, however not very successful if anything disrupts the menstrual cycle

Sterilisation Tubes that conduct the sperm from testis or the ovum from the ovary are cut and tied or clipped to prevent passage of gametes

Individuals may change their minds due to new circumstances, e.g. a new partner, death of a child.

These operations are difficult to reverse.

Infertility

Causes of infertility in females:

Abnormal hormone levels so no ovulation

Blockage of fallopian tubes

Abnormalities in the uterus lining (e.g. endometriosis)

Antibodies may develop that attack the sperm

Causes of infertility in males:

Low numbers of sperm

Blockage in sperm duct

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Abnormal sperm formation

Produce antibodies that attack their own sperm

Fertility treatments

E.g. hormones / surgery to unblock fallopian tubes or sperm ducts and assisted fertilisation

Ovulation induction

Follicles do not develop to form viable eggs = polycystic ovulation syndrome. Drugs are given to inhibit oestrogen. GnRH is released from the hypothalamus which stimulates release of FSH and LH from the anterior pituitary gland. Ovulation is induced and immature follicles are helped to develop. FSH / LH can also be given directly into the bloodstream if other options fail. By stimulating follicle development, there is a risk of multiple pregnancies

Artificial insemination

• Semen is injected into the top of the vagina or uterus through a small plastic tube.

• ICI – intra cervical insemination – semen is collected and inserted within 2 hours at top of vagina. A plastic cap is placed in vagina for several hours – this gives the sperm more chance to enter the uterus through the cervix.

• IUI – intra uterine insemination – The sperm are first ‘washed’ meaning that the sperm are separated from the semen and drawn up into an injectable device. Access to the uterus is gained via the cervix, whereby the sperm are injected directly into the uterine cavity. The sperm are then more able and more likely to find their way to the oviduct, hopefully finding an egg to fertilise.

Sperm washing

Sperm washing is a procedure used to prepare sperm for use in IUI. It allows sperm a better chance for survival and fertilization. Sperm washing separates sperm cells from a man’s semen, helping to get rid of dead or slow-moving sperm as well as additional chemicals that may impair fertilization. Once sperm has been washed, it can be used during IUI to help achieve pregnancy. There are a variety of different sperm washing procedures.

Drug therapy – men

Only about 5% of men with hormonal balance benefit from this form of treatment

• Gonadotrophin

• Antiestrogen agents

• Bromocriptine

• Testosterone

Sperm bank10

Donated sperm is frozen and used to fertilise oocytes - there is a good rate of success. However, recent changes in the law may have a negative impact on donor numbers as the identity of donors can now be revealed if the child applies to the HFEA (Human Fertilisation and Embryology Authority), once they are aged 18 or over.

Embryo storage

After initial screening for diseases human embryos can be frozen aged 1 – 6 days. They are stored in liquid nitrogen at -200oC. Correct storage is essential to prevent damage. The embryos may be thawed and implanted when the woman’s cycle is at the correct stage. There are strict laws controlling the use of embryos and both partners who gave their gametes must consent.

IVF (In vitro fertilisation)

The aim is to fuse oocytes and sperm outside the body. The cells fuse and the zygote goes onto divide forming a blastocyst. This is then artificially implanted back into the endometrium. This procedure was first carried out in 1978; the basic steps have remained the same.

1. A woman is super-ovulated using synthetic hormones so that several follicles ripen at the same time.

2. An ultra-sound probe of the vagina is used to locate ripe follicles in the ovaries. This is done under local or general anaesthetic.

3. The follicles are aspirated (sucked out), a few hours before ovulation.

4. The oocytes are removed using a suction device and placed in a test tube containing a special medium.

5. The oocytes are then maintained in separate test tubes at body temperature.

6. Sperm are prepared and at least 100 000 are added to each oocyte in a small Petri dish.

7. After 16-20 hours, the oocytes are checked to see if they have been fertilised.

8. The resulting embryos are then left to develop for two to three days in the incubator.

9. They can then be transplanted back into the uterus.

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By providing many possible embryos in the IVF process, some can be frozen and stored for later use. These can be used by women who cannot produce their own eggs after a procedure like chemotherapy. Some embryos may be donated to infertile women too.

GIFT – gamete intrafallopian transfer

Sperm and oocytes are passed directly into the oviduct and allowed to fertilise naturally. The oocytes may have been donated.

ZIFT – zygote intrafallopian transfer

Here, the zygote is created by IVF but is implanted into the oviduct and allowed to implant naturally.

Intracytoplasmic Sperm Injection (ICSI)

• ICSI is a technique sometimes used with IVF in which one sperm is injected directly into one egg in order to fertilise it. This is especially useful for men with very low sperm counts since ICSI ensures that the sperm reaches the egg directly rather than waiting for the sperm to naturally fertilise the egg. Thus, ICSI is sometimes used as a treatment method for male infertility

Multiple pregnancy

This is when more than one fetus develops in the womb at the same time. Fertility treatment - especially those involving hormones, increase the chances.

Health risks associated with multiple pregnancies include:

• High blood pressure and pre-eclampsia (dangerously high blood pressure and levels of various blood chemicals – puts mother and baby at risk), in the mother; Anaemia; Haemorrhage ; increased need for a Caesarean section; increased risk of mortality.

• Low birth weight (less than 2500g) and premature birth in babies; Higher risk of stillbirth

Selective reduction in number can be agreed if multiple fetuses result from fertility treatment. This is the abortion of one or more fetuses and can be carried out to increase the chances of survival for the other fetuses. This procedure does risk all of the fetuses and some women may miscarry or enter premature labour.

Clinics will transfer a maximum of two embryos per IVF cycle in women under 39 or three if the woman is over 40 and using her own eggs.

Remember, multiple pregnancies can occur naturally when more than one oocyte is released at once

and fertilised by different sperm – this gives non-identical or dizygotic babies. If one oocyte is

fertilised and then splits in two each cell grows into separate embryo and produce identical or

monozygotic babies. Multiple pregnancies are quite rare as usually only one oocyte is released per

month, splitting of the zygote is rare, the uterus is not designed for multiple pregnancies and as the

foetus is more at risk there is an increased chance of miscarriage.

Premature birth12

This is when birth occurs before the standard 40 week pregnancy is completed. Babies born before the 37th

week are classed as premature. This can increase the risk of certain health problems: poor neurological development; congenital heart defects due to failure of the ductus arteriosus to close after birth; respiratory distress syndrome or chronic lung disease; gastrointestinal and metabolic problems such as hypoglycaemia or feeding problems; anaemia or jaundice; infections of the urinary tract.

Pregnancy testing

Use monoclonal antibodies (MABS) to detect the presence of human chorionic gonadotrophin (HCG). The pregnancy stick is dipped into the urine (often an early morning sample as this will have the highest concentration of HCG). Any HCG in the urine will bind to specific antibodies held on the stick. The antibodies are bound to a colour bead and form a HCG-antibody complex. The urine moves up the stick by capillary action until it reaches a region of fixed immobilised antibodies. These bind to the HCG-antibody complex (if it is present) and give a coloured band. This is a positive result. Another band is used as a control and gives a coloured line with just the antibody – this acts as a control to show the test is working.

Remember monoclonal antibodies are specific so will only bind to HCG molecules; they can also detect very small amounts of HCG.

Vanishing “twin” syndrome

A twin, observed during ultrasound, may disappear later in the pregnancy. The developing fetus has died; this might be due to a chromosomal abnormality, fetal development problem or a fault with the placenta. If this occurs early in pregnancy the cells can be absorbed. However, if the death occurs later in the pregnancy this can lead to infection and premature labour.

The arguments for and against fertility treatments

There are three perspectives to consider: biological – ethical – economic

Biological Ethical Economic

Huge scientific advances have been made in assisted fertilisation

This is partly due to the decline in the fertility of couples in modern times.

Reasons for this include the increasing age of women at the time of marriage and childbearing; increase in the incidence of sexually transmitted diseases (e.g. Chlamydia) that may damage the reproductive tract in women and men.

There have been overall

Assisting fertilisation raises issues regarding questions of embryo research – time limits, when does life begin and what are the rights of an embryo.

Issues surrounding sperm banks and the future child’s rights to access information about genetic background and mode of conception.

World religions differ on ethical implications of such treatment; e.g. Catholic Church - IVF is not acceptable.

Infertility treatment is expensive, success is not guaranteed so there is often no specific end point to treatment.

Techniques such as IVF have made treatment even more expensive because of the expertise and technology necessary for these procedures.

Cost-effectiveness needs to be considered, e.g. IVF is four times more expensive than IUI but the chance of a pregnancy using IVF is also four times as great.

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decreasing sperm counts in men worldwide in the last few decades – reasons unclear? due to increased stresses of modern life or environmental pollution.

The biological implications of this can lead to the natural balance of the population been upset, natural selection does not operate and perhaps harmful genes may be bred into the population. The carrying capacity of the population may be exceeded and finite resources used up.

Some people argue women have the right to procreate, others believe it is not right to interfere with nature.

It causes increased pressure on medical resources when perhaps there are causes with greater priority.

it can cause trauma and disappointment to patients if it is not successful – along with the cost to the patient / NHS

The fate of the frozen embryos causes many ethical arguments as does the choice in the treatment of post menopausal women

Insurance companies do not consider infertility to be a medical problem. So couples do not claim for medical treatment. There is also a post code lottery, regarding IVF – the number of cycles offered on the NHS varies between authorities.

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