Problems and conditions associated with the reproductive system and development

 

Many different factors can cause problems in the development and function of the female reproductive system, including genetic and environmental factors. 

 

 

Genetic Factors

 

Genetic abnormalities can be caused by incomplete or uneven chromosome division, or the mutation of certain genes.  It usually occurs during meiosis.  Genetic abnormalities can cause monosomy and trisomy, monosomy being the lack of one chromosome from a chromosome pair, and trisomy being an extra chromosome on top of the normal chromosome pair.  The cause of this is usually nondisjunction during meiosis, and it results in one of the gametes showing monosomy of a chromosome and the other gamete showing trisomy of the same chromosome.  Generally this genotype of the autosomes or the sex chromosomes results in non viable embryos. 

 

However, there is a condition where monosomy of the sex chromosomes does produce a viable phenotype.  This syndrome is called Turner’s syndrome, and sufferers have a genotype of 45, XO.  Individuals with this genotype have primordial germ cells that degenerate soon after reaching the gonads, leading to a halt in their differentiation.  Genitalia development is female, but due to the absence of gonadal hormones the development remains infantile, and the mesonephric duct system degenerates.    

 

A Hermaphrodite has both male and female genital organs, i.e. both testis and ovaries.  The genotype of a true hermaphrodite is usually 46, XX and generally sufferers have female external genitalia.

 

 Female pseudohermaphrodites, with a genotype of 46, XX have normal internal female genitalia but the external genitalia are significantly masculanised.  This is usually due to either an excess of androgen hormones produced by the adrenal glands, or the exposure of the mother to androgenic hormones by the inappropriate treatment with anabolic steroids.  The extent of masculisation of the external genitalia varies, from basic enlargement of the clitoris, to fusion of the labia majora in order to form a scrotum-like structure.    

      

 The karyotype of a person with Turner's syndrome Image courtesy of Medical Genetics at https://medgen.genetics.utah.edu/

 

Androgen insensitivity syndrome (AIS) promotes a female phenotype at birth.  With the onset of puberty the individual develops all the characteristics of an adult woman.  However they do not start to menstruate.  This is due to the fact that these people are genetically male.  They have internal testis that secrete testosterone but due to a mutation on the X chromosome there are not enough receptors for the hormone to act on.  The testes also secret müllerian inhibitory substance, which prevent the presence of a uterus and the upper part of the vagina.   

 

Environmental factors

 

Teratogens are substances that cause disruption to normal development by damaging cells and changing chromosome structure.  They are thought to be involved in a number of developmental defects, mainly affecting the fetus by being passed across from the maternal blood stream.  If the embryo is exposed to a teratogen in the first trimester it will most likely disrupt gastrulation.  The effects will be seen in the majority of the body systems, and it is very likely the embryo will not survive.  If they affect the fetus in the second or third trimester their effects will more likely be seen in specific body systems as the basic body patterning has already occurred.  They would be more likely to survive at this point, although their life span would probably be shortened.  Examples of teratogens include radiation, which destroys chromosomes and exposure to microorganisms responsible for syphilis and rubella, which can cause major abnormalities.  Some chemicals can be teratogens, if the fetus is exposed to them at vulnerable stages of development.  One example is thalidomide, a drug used for sleeplessness and nausea.  If taken by the mother this crosses the fetal/maternal blood barrier to severely affect limb development of the fetus. 

 

Many pesticides, herbicides and heavy metals can also harm fetal development.  Fetal alcohol syndrome is the result of the mother drinking heavily throughout her pregnancy.  It can lead to severe developmental abnormalities, including cardiovascular defects, neurological disorders and skeletal problems.  Smoking introduces harmful toxins to the baby, as well as lowering the amount of oxygen the baby receives, leading to stunted growth and increasing the chance of the baby being born prematurely.   

 

 

Reproductive Disorders

 

There are various signs that indicate that a woman may have a reproductive system disorder:

 

• Bleeding from the vagina outside normal menstruation: This can be a symptom of a tumour, endometriosis, pelvic inflammatory disease or the use of oral contraceptives.

 

• Pain in the pelvis:  This may be a symptom of pelvic inflammatory disease, an ectopic pregnancy that has burst, an ovarian cyst, or inflammation of the uterine tubes.

 

• Amenorrhea: May be due to pregnancy, the menopause, Anorexia Nervosa, or very overweight women.

 

• Infertility: May be related to abnormal hormone secretion, defects in the reproductive tract or a variety of ovarian disorders. 

 

Ovarian and Uterine Cancer

 

Ovarian cancer is one of the most common reproductive cancers among women.  It is probably the most dangerous due to the fact that it is often left undetected until it is very advanced.  If the tumour has originated from ovarian tissue or abnormal oocytes then it is likely that the cancer can be dealt with, and the prognosis will generally be good.  However the majority of ovarian cancer is the result of proliferation of epithelial tissue, which is much harder to treat, and even if the cancer does disappear it is very likely it will return.  One of the reasons it can go undetected for so long is the absence of an effective screening technique. 

 

 

If caught early, the infected ovary can be removed, as well as the uterine tube.  In more advanced cancer both ovaries and the entire uterus are usually removed.  In addition to this radiation and chemotherapy are usually undertaken.  If the ovarian cancer is not caught until very late, stage III or IV, both ovaries, the uterus and the omentum are removed, and the patient must undergo intensive chemotherapy.

 

Uterine tumours are quite common, but are most often benign and cause no problems.  They usually involve smooth muscle and connective tissue cells, and if small they can go completely undetected.  However sometimes the tumours can enlarge due to stimulation by oestrogen, and cause blockages of the uterine tubes, or pressure on blood vessels which may lead to complications.  If detected in younger women these are removed or targeted by drugs to try and preserve fertility.  If found in older women, they often undergo a hysterectomy.  Tumours found in uterine epithelial tissue are called polyps and usually go undetected as they are very small.  If enlargement does occur, which often results in bleeding, the polyps can be removed. 

 

 

The occurrence of malignant uterine tumours is quite uncommon.  There are two types, endometrial and cervical cancer.  Endometrial cancer affects the endometrial lining and is quite invasive.  It is more likely to affect older women, as oestrogen therapy used to treat osteoporosis is a major cause, increasing the risk by 2-10 times.  Like ovarian cancer, there is not a proper screening test for endometrial cancer, and it is usually only detected by examination of a biopsy of endometrial tissue.  If caught early the uterus is removed, and the sufferer undergoes radiotherapy.  Chemotherapy does not aid in tackling endometrial cancer.

 

Cervical cancer is the most common reproductive cancer in younger women, and is often the result of a woman having many sexual partners, and thus getting a viral infection of one of many human papillomaviruses (HPV’s).  The screen to test for cervical cancer is a Pap smear, which involves taking a sample of cervical lining cells to be analysed.  The most common symptoms include vaginal bleeding, especially after intercourse, pelvic pain and vaginal discharge, although these only occur quite late on in the progression of the disease.  Often abnormal but not cancerous lesions are detected on Pap smears, and these are treated to try and prevent the development of these into cervical cancer.  If the cancer is caught early the most effective treatment is the removal of the part of the cervix that is affected.  If it is only found in the later stages a hysterectomy is usually performed, and the sufferer undergoes intensive radiation therapy as well as chemotherapy and lymph node removal.      

 

Polycystic Ovarian Syndrome (PCOS)

 

This is a condition associated with multiple cysts on the ovaries.  It is also known as the Stein-Leventhal syndrome.  During normal ovarian function several follicles develop each month until one becomes dominant and matures fully, while the rest break down.  In PCOS many follicles develop each month, but not enough to fully mature and release an egg.  Therefore ovulation does not occur.  The cysts on the ovaries are not actual cysts but follicles that have failed to develop.  There is generally an imbalance in the hormones produced by the ovaries, often with raised levels of testosterone.  PCOS is very common, with as many as 1 in 10 women suffering from it to some extent.  It has been found to be the most common cause of ovulation failure and therefore infertility in women.  

 

 Pelvic Inflammatory Disease

 

This is a collective name for an inflammatory disease of the female reproductive system.   Usually the cervix acts as a plug that prevents bacteria from moving up from the vagina to the internal reproductive organs.  However if bacteria does come in to contact with the internal organs it can lead to inflammation and infection.  If it affects the fallopian tubes it can lead to it becoming very difficult for the woman to get pregnant.  There are many ways a woman can get pelvic inflammatory disease.  The main cause is when the woman becomes exposed to a sexually transmitted disease such as Gonorrhea or Chlamydia.  These are carried in a man’s semen and during sexual contact the bacteria can lead to inflammation of the cervix.  The cervix can no longer act as a barrier for the bacteria and the internal organs become infected.  Rarely a woman can get pelvic inflammatory disease without coming in to contact with a sexually transmitted disease.  Sometimes it can occur when the organs are infected by bacteria after giving birth or having an abortion, if the cervix is treated for an abnormal Pap smear, or if an intrauterine device is inserted.        

 

Sexually Transmitted Diseases (STI’s)

 

Sexual intercourse can spread a number of different viral, bacterial and fungal infections collectively known as STI’s.  There are over twenty known STI’s, each with varying symptoms.  Some examples include gonorrhea, Chlamydia, Syphilis, which if untreated can be deadly, Herpes, and genital warts.  HIV can also be transmitted through intercourse.

 

 Ectopic Pregnancy

 

In normal implantation the fertilised egg implants into the endometrial lining of the uterus.  However in a low percentage of cases implantation can occur abnormally.  This is known as an ectopic pregnancy.  Most ectopic pregnancies happen in the ampulla region of the uterine tubes, although the fertilised egg can implant anywhere between the fimbriated end of the tube nearest the ovaries to the uterotubal junction by the uterus.  This usually occurs in woman with endometriosis, a condition where endometrial tissue is found in abnormal places, or sufferers of pelvic inflammatory disease.  At the beginning of pregnancy the woman shows no signs of the abnormality.  However by about two months the embryo has grown to the point where it is stretching the tube so much it causes acute abdominal pain.  If the tube ruptures it leads to a hemorrhage which can be life threatening to the woman. 

 

More rarely the embryo implants into the ovary itself, or in the abdominal cavity, the most common location being in the abdomen just behind the uterus.  This is incredibly dangerous due to the likelihood of a severe hemorrhage as the baby grows.    Sometimes the embryo can implant in the uterus close to the cervix.  Embryonic development is likely to be normal but the placenta can form a slight covering over the cervical canal.  This can result in a hemorrhage late in the pregnancy and if it goes untreated would most likely cause the death of both the fetus and the mother due to premature detachment of the placenta.           

 

 

An ectopic pregnancy in the uterine tube Image courtesy of Wikimedia under the creative commons license https://upload.wikimedia.org/wikipedia/commons/3/33/Ectopic.gif