2014 Group Project 9

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2014 Student Projects
2014 Student Projects: Group 1 | Group 2 | Group 3 | Group 4 | Group 5 | Group 6 | Group 7 | Group 8
The Group assessment for 2014 will be an online project on Fetal Development of a specific System.

This page is an undergraduate science embryology student and may contain inaccuracies in either description or acknowledgements.

Genital

Abnormalities

We discuss both male and female genital abnormalities internally or externally, that may occur during fetal development. The abnormalities have been identified as disorders of sex differentiation(DSD), associated with congenital conditions in the atypical development of chromosomal, gonadal or phenotypical sex [1], [2].

The content will cover most common abnormalities and then also the rare cases. Most genital abnormalities have a high risk in affecting fertility of both sexes. Currently there are a variety of methods applied to ensure that infertility can be treated and this will be mentioned.

FEMALE

Abnormalities of the Uterus and Vagina

Abnormalities of the Uterus and vagina are cause by inadequate fusion or regression of Mullerian duct may result as the following;

  • double uterus and double vagina
  • double uterus
  • bicornate uterus
  • septated uterus
  • unicornate uterus
  • cervical atresia

Mullerian agenesis

Mullerian agenesis also known as ‘Mayer-Rokitansky-Kuster-Hauser’ syndrome, vaginal agenesis or Mullerian aplasia, is presented in the absence of the uterus or vagina or in some case even both. This is due to the unsuccessful development of the Mullerian ducts which then causes certain parts of the reproductive system to be underdeveloped. It is present in 1 of 4000-10 000 women. This condition also uses dilation therapy and following the neovaginal approach with the reconstruction of the vagina in its treatment strategies [3].

Vaginal agenesis

Vaginal agenesis is a rare condition involving the underdevelopment of the vagina. It is commonly cause by a combination of Rokitansky (Mullerian agenesis) and androgen insensitivity syndromes [4]. To ensure effectiveness in treatment, it’s advised after or during adolescence, procedures consist of vaginal dilation shown a success rate of 80% and low risks. In cases where such methods are ineffective then vaginal reconstruction is implemented as a final option for patients [5].

Turners syndrome

A chromosomal disorder occurring among women due to the absence of the whole or part of the sex chromosome (X). The condition is characterized by short stature, cardiovascular malformations, amenorrhea and estrogen insufficiency [6]. It is prevalent in 1 of 2000 live births among females [7]. Management of the syndrome depends on the extent of the condition the individual will present. Therefore treatment will vary, for short stature biosynthetic growth hormone is utalised in growth hormone. The most common cardiac malformations are bicuspid aortic valve, coarctation of the aorta and aortic stenosis that are all surgically treated. Generally patients are advised to see pediatricians, endocrinologists and many other clinicians depending on the severity of the condition, to discuss strategies to manage the syndrome [8].

Swyer Syndrome

Swyer syndrome (46 XY, gonadal dysgenesis) is a type of hypogonadism disorder in which an individual from birth is phenotypically female with unambiguous genital form and normal mullerian structures. The condition is usually observed during adolescence since the gonads have no hormonal or reproductive function amenorrhea occurs and puberty is delayed [9]. It has been found that 10-20% of women with this condition have a deletion of the SRY gene in the DNA-binding site. In other cases the SRY gene is normal however mutations may present in different determining factors. Managing the syndrome consists of hormone replacement therapy (including estrogen and progesterone), to ensure bone mineral density is maintained and uterine size and shape is improved [10].

Also related include;

Polycystic Ovarian Syndrome

The Female reproductive system showing a normal ovary compared to one that is affected by Polycystic Ovarian Syndrome

A metabolic endocrine disorder with an immense variety of phenotypes presented. The disorder has an imbalance in female sex hormones and a resistance to insulin. Most importantly it affects the female reproductive system, with issues associated with infertility and menstrual irregularities. The treatments implemented depend on the clinical manifestations each patient develops. Insulin-sensitizing agents are among the treatments used these include Metformin, Rosiglitazone and Piglitazone all have shown to be effective [11].

MALE

Cryptorchidism

The sites where Cryptorchidism may occur

Involves the absence of both or single testis to descend into the scrotum, the testes can be ectopic, incompletely descended, absent or atrophic. It is possible that sometimes the cryptrodism may be spontaneously corrected by 3 months of age. The abnormality can occur as a result of a number of factors including maternal, genetic or environmental [12]. The descendence of testis occur in two stages; in the first stage insulin like hormone attaches the testis to the inguinal ring this is through gubernaculum development. Following is the inguinoscrotal stage that requires testicular androgens [13].

Treatment includes human chorionic gonadotropin or gonadotroping-releasing hormones, these are not the most beneficial or advised approach. Surgical repair is intended to apply the safest and least invasive methods, focusing on repositioning the undescended testicle/s to their normal position in the scrotum. Such surgeries are recommended in early life and have proved to be most effective, with 75%+ success. The therapy used to relocate the testis into the scrotum is known as ‘Orchiopexy’, others include one-stage Fowler Stephens and two-stage FS Orchidopecy. However there are concerns with long-term effects which include infertility and testicular cancer later in life as a result of the procedure [14].

Hypospadias

In males the most common congenital malformation of the external genitalia is hypospadias, it’s also the second most common developmental disorder. It occurs due to the midline fusion of the male urethra, as a result the urethral meatus is misplaced. There are several sites where this abnormality may occur: granular, penile, penoscrotal, scrotal and perineal. [15] Its believed that genetic factors contribute to the presence of the disorder, however endocrine and environmental factors are also of significance. [16] Treatment The surgical methods currently used to treat distal hypospadias, include tabularized incised plate and meatal advancement and glansplasty intergrated repair. For proximal forms two staged procedures are employed. [17]

Klinefelter

Klinefelter is a genetic disorder caused by the addition of an X chromosome among males (47, XXY, XXY,XXXXY, XXYY), due to the inability of the extra chromosomes to detach throughout meiosis. It is believed to have an origin from either parent. The abnormality has a wide range of phenotypic variations, that typically include infertility, small testes, gynecomastia and hypergonadotropic hypogonadism [18]. An early diagnosis is important in order for treatment to be commenced right away. The treatment implemented involves Testosterone replacement therapy, which assists in easing some of the features, although infertility is still an issue. The fertility options consist of IVF, where males undergo testicular sperm extraction, cryopreservation of sperm containing semen or testicular tissue during adolescence [19].

Peyronie’s Disease

The acquired disease occurs due to fibrotic plaque formations in the tunica albuginea of the penis. This leads to sexual dysfunction, a loss in penile flexibility, shortening and penile malformations [20]. The penis is curved upward as a result of the plaque structure. Adult males are at risk of the condition where about 3.2-8.9% are affected among the population [21]. Strategies applied vary in the extent of the deformities; some procedures involve grafting in the lengthening of the penis, plaque removal and prosthesis implantation in erectile dysfunction [22].

BOTH

Congenital adrenal hyperplasia

The condition is caused by a deficiency in 21-Hydroxylase, a genetic disorder of steroidogenesis. Occurs due to mutations in genes that encode enzymes that take part in adrenal steroid synthesis therefore there is a loss of function [23]. The deficiency is from mutations in CYP21A2, thus the clinical characteristics may vary. In females it results in the ambiguity of the female genitalia, fused labia majora, larger clitoris and common urogenital sinus [24]. Steroid 21-OHD deficiency is examined in-utero and then prenatal treatment with dexamethasone is administered. This is a safe method used and decreases the risk of ambiguous genitalia in females [25]. Among males symptoms aren’t present at birth a side from possible penile enlargement and slight hyperpigmentation [26]. Generally male patients also require the administration of glucocorticoid and mineralocorticoid therapies [27].

Hydrocele

Hydrocele occurs when the space between parietal and visceral layers of tunica vaginalis accumulates an abnormal amount of serous fluid. Normally caused by an imbalance in the processes of production and reabsorption of fluid or varicocelectomy. To manage the condition treatments focus on ensuring draining any excess fluid and inhibiting reaccumulation. Techniques used involve sclerotherapy and hydrocelectomy [28]. In females it is a very rare condition, occurs in the ‘Canal of Nuck’, a part of the inguinal canal containing a section of the processus vaginalis. A swelling is present on the labia major or inguinal ring. Techniques applied to treat the condition in females involve ligation of the processus vaginalis neck and the hydrocele is surgically resected [29].


Also related include;

Kallmann syndrome

Kallmann’s syndrome is a heterogenous disease expressed during puberty due to a combination of hypogonadotropic hypogonadism and anosmia. The genetic disease is responsible for infertility and the inability to smell. Seems to have affects on 1 in 10 000 males and 1 in 50 000 females [30]. It occurs during embryonic development at a time in which hypothalamic neurons (gonadotropin-releasing hormones) are unable to migrate into the hypothalamus. Currently there are no available treatments for the olfactory deficit, however among males hormone replacement therapy is implemented with human chorionic gonadotropin, human menopause gonnadotropin and testosterone undecanoate [31]. In females treatment focuses on maintaining and inducing secondary sex characteristics [32].

Hypogonadotropic hypogonadism

The condition results in a failure to secrete gonadotropin such as luteinizing (LH) and follicular stimulating hormones (FSH), which then reduce the gonadotropin levels [33] . This indicates possible issues with the hypothalamus or the pituitary gland. It may occur in conjunction with Kallmann’s syndrome or a decreased gonadotropin-releasing hormone (GnRH). In males treatment methods depend on how the condition is presented and whether it’s associated with another abnormality. Generally the therapies may require testosterone in cases with micropenis and to generate spermatogenesis gonadotropin replacement is utalised. Hypogonadotropic Hypogonadism is rare among females, however it may be presented thus similar treatment options are available. Treatments consist of gonadotropins administration of FSH and LH, to ensure successful occyte formation [34].

References

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