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  1. 1. 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. 1
  2. 2. 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). 2
  3. 3. 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. 3
  4. 4. 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 end not fully differentiated ; of process mature sperm produced / secondary oocyte produced / division division completed division not completed / completed at fertilisation ; no polar bodies / equal polar bodies / unequal divisions ; divisions millions / large numbers only one, at a time / per month / fixed number; produced 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. Key phrase to use when explaining the action of hormones – NEGATIVE FEEDBACK 4
  5. 5. • 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 Binds to follicle cells and stimulates follicle to mature LH Anterior pituitary and produce oestrogen 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 • 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 5
  6. 6. • 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. 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. 6
  7. 7. 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 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. 7
  8. 8. 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 Combination of synthetic Increased risk of thrombosis and oestrogen and progesterone, breast cancer - increasing the Birth control pill creates artificial negative load on medical facilities and feedback and prevents ovulation society Reduce the risk of sexually transmitted disease, but may be Condoms / diaphragm / femidom Acts as a barrier to prevent sperm unacceptable from religious from meeting egg viewpoints Offer no protection from STDs, carry increased risk of thrombosis Injections and implants, e.g. Contraceptive hormones, given and breast cancer which affects Norplant and DMPA (Depo- subcutaneously, last up to 3 years society and medical facilities Provera) 8
  9. 9. May cause uncomfortable uterine pains and excess bleeding may be IUD Prevents implantation of embryo considered unethical since the either physically or by presence of embryo is already formed copper The morning-after pill Used if contraceptive device fails Removes responsibility and may or if not used. Large doses of be considered unethical. Causes steroids prevents implantation extreme stomach pains and sickness. None, however not very successful if anything disrupts the Natural rhythm method Intercourse during ovulation menstrual cycle avoided Individuals may change their minds due to new circumstances, Sterilisation Tubes that conduct the sperm e.g. a new partner, death of a from testis or the ovum from the child. ovary are cut and tied or clipped to prevent passage of gametes 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 • 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 9
  10. 10. 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 bank 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 10
  11. 11. 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. 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 11
  12. 12. 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 birth 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. 12
  13. 13. 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 Assisting fertilisation raises issues Infertility treatment is expensive, been made in assisted fertilisation regarding questions of embryo success is not guaranteed so there research – time limits, when does is often no specific end point to This is partly due to the decline in life begin and what are the rights treatment. the fertility of couples in modern of an embryo. times. Techniques such as IVF have Issues surrounding sperm banks made treatment even more Reasons for this include the and the future child’s rights to expensive because of the increasing age of women at the access information about genetic expertise and technology time of marriage and background and mode of necessary for these procedures. childbearing; increase in the conception. incidence of sexually transmitted Cost-effectiveness needs to be diseases (e.g. Chlamydia) that World religions differ on ethical considered, e.g. IVF is four times may damage the reproductive implications of such treatment; more expensive than IUI but the tract in women and men. e.g. Catholic Church - IVF is not chance of a pregnancy using IVF is acceptable. also four times as great. There have been overall decreasing sperm counts in men Some people argue women have Insurance companies do not worldwide in the last few decades the right to procreate, others consider infertility to be a medical – reasons unclear? due to believe it is not right to interfere problem. So couples do not claim increased stresses of modern life with nature. for medical treatment. There is or environmental pollution. also a post code lottery, regarding It causes increased pressure on IVF – the number of cycles offered The biological implications of this medical resources when perhaps on the NHS varies between 13
  14. 14. can lead to the natural balance of there are causes with greater authorities. the population been upset, priority. natural selection does not it can cause trauma and operate and perhaps harmful genes may be bred into the disappointment to patients if it is not successful – along with the population. The carrying capacity of the population may be cost to the patient / NHS exceeded and finite resources The fate of the frozen embryos used up. causes many ethical arguments as does the choice in the treatment of post menopausal women 14