Obs & Gynae - Physiology

Question 1

In order to understand better the pathophysiology of menstrual disorders, it’s important to learn how the menstrual cycle works, and what hormones are responsible for regulating the activity of the menstrual cycle.

a) . What is the typical duration of the menstrual cycle?
b) . At what age do girls get their first menstruation? and at what age do females become menopausal?

Answer 1

a) . 21-35 days
b) . First menstruation (menarche): 11-15 yrs old

Menopause: 44-55 yrs old

Question 2

What hypothalamic-pituitary axis is responsible for regulating the menstrual cycle?

Answer 2

The Hypothalamic-Pituitary-Gonadal (HPG) Axis

Question 3

What hormones are released by the HPG axis in females?

What hormone is released in male?

Answer 3

Female: Hypothalamus –> GnRH –> anterior pituitary –> LH and FSH –> Gonads –> Oestrogen and Progesterone

Male: Everything is the same except that the gonad releases testosterone

Question 4

What does FSH do in the menstrual cycle? (In other words, what is its role?)

Answer 4

• FSH binds to granulosa cells to stimulate follicle growth (hence the name Follicle-Stimulating Hormone)
• Converts androgens (produced by theca cells) to oestrogens
• Stimulates inhibin secretion from the granulosa cells of the ovarian follicles. The inhibin, in turn, suppresses FSH
  
  • This is important as the inhibin being released prevents FSH from stimulating more than one dominant follicle. We just need one mature follicle for each menstrual cycle as women have only a finite number of eggs

Question 5

What does LH do in the menstrual cycle? What role(s) does it play?

Answer 5

• Acts on theca cells to stimulate the release of androgens, which are then converted to oestrogen by granulosa cells (by FSH)
• LH surge triggers ovulation
• It maintains corpus luteum (see image) after ovulation
  
  • The corpus luteum releases oestrogen, progesterone and inhibin in large quantities. It regresses after 12-14 days unless fertilisation takes place and hCG is released (after implantation) which prevents its breakdown

Question 6

a) . What does oestrogen do in the menstrual cycle
b) . How does the level of oestrogen determine the level of GnRH secretion in the menstrual cycle?

Answer 6

Oestrogen is the predominant hormone in follicular phase:

• Oestrogen is released by granulosa cells as the follicle develops, hence, the more the follicle develops (the bigger it is), the more the oestrogen is released
• Low-to-moderate levels of oestrogen –> negative feedback on the HPG axis –> reduces GnRH secretion –> LH + FSH decreases
• High levels of oestrogen (in the absence of progesterone) –> positive feedback on the HPG axis –> increases GnRH secretion –> LH surge –> ovulation
  
  • ​Note that the FSH levels will only increase slightly as it’s also being inhibited by inhibin)
• Oestrogen also causes LH receptors to be expressed on granulosa cells, so that after ovulation when the corpus luteum is formed, LH can act on granulosa lutein cells to produce progesterone during the luteal phase
• In the luteal phase, the corpus luteum releases oestrogen, progesterone and inhibin in large quantities. High levels of oestrogen in the presence of a high progesterone level –> negative feedback on the HPG axis –> reduces GnRH secretion –> LH + FSH decreases

Question 7

What does progesterone do in the menstrual cycle?

Answer 7

Progesterone is the predominant hormone in luteal phase:

• Progesterone is produced by granulosa lutein cells of the corpus luteum in large quantities in response to LH
• It increases the inhibitory effect of low oestrogen and prevents the stimulatory effect of high oestrogen. Simply put, it promotes negative feedback on oestrogen to _**reduce GnRH when present_

Question 8

Describe the physiology of the menstrual cycle. What happens in early follicular phase

Answer 8

Early follicular phase:

• At the start of the cycle, follicles development begins due to a rise in FSH
  
  • FSH rises because the corpus lutuem from the previous cycle degenerates so it no longer produces any inhibin. Without inhibin, FSH level rises
• As the follicle develops i.e. gets bigger, the number of granulosa cells increases, and theca interna and externa appear
  
  • Androgen production begins in the theca interna and then the granulosa cells convert the androgens to oestrogens, causing the oestrogen levels to rise. The endometrial lining, in response to a rising oestrogen, begins to thicken in the proliferative phase of the uterine cycle
• The oestrogen levels are still low at this stage as the follicle is still developing, so it inhibits GnRH secretion through negative feedback

Question 9

What happens during late follicular phase?

Answer 9

Late follicular phase:

• As the follicle continues to develop under the influence of FSH, more granulosa cells are present and these cells produce increasing amounts of oestrogen and inhibin
• When the oestrogen reaches a level where it’s high enough to stimulate GnRH secretion from the hypothalamus through positive feedback, it causes LH to rise (LH surge). The FSH only rises a little as the inhibin being released prevents FSH from stimulating more than one dominant follicle (only one dominant follicle can survive and continue to maturity and complete each menstrual cycle, other follicles become polar bodies)
• The LH surge triggers ovulation where the secondary (mature) oocyte bursts out from the Graafian follicle and travels to the fallopian tube by fimbria. Here in the fallopian tube it remains viable for fertilisation for 24 hrs
• Oestrogen also causes LH receptors to be expressed on granulosa cells, so they become more responsive to LH

Question 10

What happens in the early luteal phase of the menstrual cycle?

Answer 10

Early luteal phase:

• After ovulation, the ovarian follicle is luteinised to form the corpus luteum
• The granulosa lutein cells in the corpus luteum secretes oestrogen, progesterone and inhibin in large quantities. Increased oestrogen and progesterone help maintain the endothelial lining and turning it secretory (this is when the secretory phase of the uterine cycle starts). The inhibin inhibits the FSH, stalling the cycle in anticipation of fertilisation
  
  • Secretory endometrium means that the cells on the inside of the uterus are producing substances necessary to support implantation of an egg should fertilisation occur
• Normally, the high levels of oestrogen alone would cause positive feedback on GnRH secretion, but the presence of progesterone (along with high oestrogen) promotes the negative feedback of oestrogen, inhibiting the GnRH secretion. Without GnRH, LH falls and the gamete doesn’t develop any further and it just sits in the ‘waiting phase’ ready to be fertilised

Question 11

What happens in late luteal phase if:

a) . Fertilisation doesn’t occur
b) . Fertilisation occurs

Answer 11

Late luteal phase:

• a). After 14 days in the luteal phase, if fertilisation doesn’t occur the corpus luteum degenerates so the levels of oestrogen, progesterone and inhibin falls. Progesterone withdrawal means that the uterus lining is no longer maintained and sheds causing menstrual bleeding
• As the steroids fall, the negative feedback that inhibits GnRH secretion is lost, so LH and FSH begins to rise again and the cycle restarts. (Note that LH may not rise at all as the follicles are just starting to develop, so oestrogen level is really low. FSH will rise due to a lack of inhibin)
• (b). If fertilisation and implantation take place, the syncytiotrophoblast of the embryo produces human chorionic gonadotrophin hormone (hCG) that exerts luteinising effects and so prevents the breakdown of corpus luteum. The corpus luteum continues to secrete oestrogen and progesterone until the placenta takes over the production of these steroid hormones at around 4 months of gestation

Question 12

The duration of the menstrual cycle varies from one individual to another, but most people have a menstrual cycle of 21-35 days.

Which phase of the menstrual cycle is responsible for giving this variation?

Answer 12

The follicular phase

(The luteal phase is ALWAYS the same in every woman, lasting 14 days, so what gives this variation in the duration of the menstrual cycle is the follicular phase. Some women have shorter follicular phase while others have slightly longer follicular phase)

Question 13

There are 2 layers of the endometrium. What are they? Which layer is the one that sheds during menstruation?

Answer 13

Stratum functionalis (this layer sheds during menstruation)

Stratum basalis (this layer allows the functional layer to regrow when a new cycle begins)

Question 14

Describe the uterine cycle. What phases are there?

Answer 14

Proliferative phase:

The endometrium proliferates so the stratum functionalis thickens in response to oestrogen produced by the ovary. Simple, straight glands develop inside the endometrium but as this phase continues the stratum functionalis of the endometrium becomes even thicker and the glands become coiled

Secretory phase:

After ovulation, the glands become more pronounced and coiled and become secretory (so mucus gets thickened) due to progesterone

Towards the end of this phase, when the hormones produced by the corpus luteum falls, the glands lose their structure and the endometrium sheds its functional layer

Menses:

It occurs in the absence of fertilisation once the corpus luteum has broken down and the internal lining of the uterus is shed. Menstrual bleeding usually lasts between 2-7 days with 10-80 mL blood loss

Question 15

Which hormone (oestrogen vs progesterone) regulates the follicular/ proliferative phase of the menstrual cycle?

Answer 15

Oestrogen

Question 16

What physiological changes does oestrogen bring during the follicular/ proliferative phase?

Answer 16

Role of oestrogen in follicular/ proliferative phase:

• Stimulate mildly anabolic metabolic changes, depress appetite and maintain bone structure
• Increased growth and motility of the myometrium
• Thickening of the endometrium and increase in number and size of glandular invaginations. The cells secrete a watery fluid conducive to sperm
• Thin alkaline cervical mucus to facilitate sperm transport
• Increased secretion and muscular contraction in the fallopian tube
• Increased growth and motility of fallopian cilia
• Increased mitotic activity in the vaginal epithelium

Question 17

What physiological changes does progesterone bring during the luteal/ secretory phase?

Answer 17

Role of progesterone in luteal/ secretory phase:

• Stimulate a mildly catabolic metabolic change, elevates basal body temperature, promote change in salt and water excretion which may, in combination with oestrogen lead to net Na+ and water retention
• Further thickening of the endometrium, increased secretion and development of spiral arteries
• Further thickening of the myometrium but reduces myometrial motility (you want a stable environment for the zygote to grow)
• Reduces fallopian tube motility, secretion and cilia activity
• Thick acidic cervical mucus, inhibiting sperm transport to prevent polyspermy

Question 18

What is gametogenesis?

Answer 18

Gametogenesis occurs when a haploid cell (n) is formed from a diploid cell (2n) through meiosis

Gametogenesis in the male is called spermatogenesis while that in the female is called oogenesis

Question 19

a) . Describe the process of spermatogenesis
b) . How long does the process take?

Answer 19

Spermatogenesis:

Men start producing sperm as they approach puberty, which is usually from 10-16 yrs old

a) . Sperm production begins in the seminiferous tubules of the testes
* The primordial germ cells (PGCs) in the germinal epithelium give rise to Type A dark spermatogonia (2n), cells that initiate spermatogenesis
* Type A dark spermatogonia (2n) –> mitosis –> Type A pale spermatogonia (2n) –> mitosis –> Type B spermatogonia (2n)
* Type B spermatogonia (2n) –> mitosis –> some more spermatogonia (to keep the bank full so that they won’t lose the source of spermatogonia) + 1^o spermatocytes (2n)
* 1^o spermatocytes (2n) –> meiosis I –> 2^o spermatocytes (n)
* 2^o spermatocytes (n) –> meiosis II –> spermatids (n)
* Throughout the series of mitotic and meiotic events, cytokinesis (cell separation) is incomplete, which means that successive cell generations remain joined together by cytoplasmic bridges (i.e. they maintain contact throughout differentiation)
* The spermatogonia and spermatids remain embedded deep within the sertoli cells throughout their development. This way, the Sertoli cells can support, protect, and nourishes the spermatogonia and the spermatids with nutrition, and also assist in the maturation of spermatids into spermatozoa (spermiogenesis) and the subsequent release of the spermatozoa

• Spermatogenesis is regulated by LH secreted by the pituitary gland
  
  • LH binds to Leydig cells around each seminiferous tubule and stimulates the secretion of testosterone which in turn binds to Sertoli cells to promote spermatogenesis
• FSH is also produced - it binds to Sertoli cells and stimulates testicular fluid production and synthesis of androgen receptor proteins
  (b) . Spermatogenesis takes about 70 days, therefore in order for sperm production to be continuous and not intermittent, multiple spermatogenic processes are occurring simultaneously within the same seminiferous tubule, with new groups of spermatogonia arising every 16 days (spermatogenic cycle). Each of these populations of spermatogenic cells will be at different stages of spermatogensis. This ensures that men will always be ready to procreate when females are the most fertile around the time of ovulation

Question 20

What are the functions of Sertoli cells?

Answer 20

Functions of Sertoli cells:

• Form the blood-testis barrier - this is very important as:
  
  • It prevents the immune system of the male from recognising the sperm as foreign (the sperm are genetically different from the male and will express different surface antigens)
  • It also prevents substances in the blood from affecting the developing sperm. These include hormones or waste products
• Support, protect, and nourishes the spermatogonia and the spermatids with nutrition
• They secrete:
  
  • Anti-Mullarian hormone during the early stages of foetal life
    
    • This causes Mullarian duct (paramesonephric duct) to degenerate
  • Inhibin after puberty, and work together to regular FSH secretion
  • Androgen-binding protein (also called testosterone-binding globulin) - increases testosterone concentration in the seminiferous tubules to stimulate spermatogenesis
  • Estradiol - aromatase from Sertoli cells convert testosterone to 17 beta-estradiol to direct spermatogenesis
• DNA repair
• Immunomodulatory properties
  
  • Sertoli cells produce a wide range of molecules (either on their surface or soluble) that are able to modify the Immune system (IS), and changes in the immune response in the tubule is needed for successful sperm cell maturation

Question 21

To illustrate the process of spermatogenesis better, please see the image attached!

Answer 21

I have attached below an image of what germinal epithelium looks like in a male. You can see that one germinal epithelial cell consists of the basement membrane which forms the wall of the seminiferous tubule, cells belonging to the spermatogenic cell lineage (they eventually form spermatozoa), and Sertoli cells

1 = Basement membrane

2 = Spermatogonia

3 = 1^o spermatocyte

4 = 2^o spermatocyte

5 = Spermatid

6 = Mature spermatid

7 = Sertoli cell

8 = Tight junctions

Question 22

How many spermatozoa are produced from one spermatogonium?

Answer 22

4 spermatozoa

Question 23

What is spermiogenesis?

Describe the process of it

Answer 23

Spermiogenesis is the final stage of spermatogenesis, which sees the maturation (remodelling and differentiation) of spermatids into mature spermatozoa. Changes include:

• Formation of the acrosome - contains enzymes that assist in penetration of the egg and its surrounding layers (zona pellucida) during fertilisation
• Condensation of the nucleus
• Formation of the neck, middle piece, and tail
• Shedding of most of the cytoplasm as residual bodies that are phagocytosed by Sertoli cells
• When spermatozoa are fully formed, they enter the lumen of the seminiferous tubules and are pushed towards the epididymis by contractile elements in the wall of the seminiferous tubules and are stored there

Question 24

Describe the process of oogenesis

Answer 24

Oogenesis differs from spermatogenesis in that it begins before birth

Before birth

• Primordial germ cells (which originate in the yolk sac of the embryo) migrate to the primordial female gonad and differentiate into oogonia
  
  • These oogonia (all derived from a single cell) are arranged in clusters surrounded by follicular cells, originating from surface epithelium covering the ovary - see image
• Oogonia undergo a number of mitotic divisions to produce 1^o oocytes (2n) and more oogonia (to keep the bank full so that they won’t lose the source of oogonia). The 1^o oocytes then undergo meiosis I BUT are arrested at prophase I
• During the next few months, replication of mitosis peaks at around 20 weeks, causing a rapid increase in the number of oogonia and 1^o oocytes (about 7 million of them!). Cell death then occurs after this peak leaving just 2 million 1^o oocytes at birth
• Primary oocytes are arranged in the gonad as clusters and each of them has follicular cells surrounding it - we now call these ‘primary follicles’

During childhood

• During childhood, further atresia occurs, leaving just 40,000 eggs by the beginning of puberty, and < 500 of them will be ovulated

At puberty

• Once puberty begins, a number of 1^o oocytes (15-20 of them) begin to mature each month, BUT only one of them reaches full maturation to become an oocyte
  
  • The 1^o oocytes undergo 3 stages:
    
    • Pre-antral stage
      
      • The 1^o oocyte is still in meiosis I but will grow significantly in this stage
      • The follicular cells grow and proliferate to form a stratified cuboidal epithelium - we now call these ‘granulosa cells’, they secrete glycoproteins that form the zona pellucida around the 1^o oocyte
      • Surrounding connective tissues also differentiate to become the theca folliculi, a specialised layer of cells that is responsive to LH and can secrete androgens under its influence
    • ​Antral stage
      
      • ​Fluid-filled spaces form between granulosa cells, these eventually combine together to form a central fluid filled space called the antrum​​​​ - we now call the follicles ‘secondary follicles’
      • In each month, one of these secondary follicles becomes dominant and develops further under the influence of FSH, LH and oestrogen
    • Pre-ovulatory stage
      
      • Induced by the LH surge
      • Meiosis I of 1^o oocyte is now complete, giving rise to a haploid 2^o oocyte and the 1st polar body (far less cytoplasm)
      • The haploid 2^o oocyte and the polar body then undergo meiosis II. The initial polar body will replicate to give 2 polar bodies BUT the 2^o oocyte arrests in metaphase II - this happens 3 hrs before ovulation!
• During ovulation, an LH surge occurs and increases collagenase activity. The collagenase breaks down the collagen in the follicular wall. This, in combination with muscular contractions of the ovarian wall, results in the 2^o oocyte being released from the Graafian follicle inside the ovary. The 2^o oocyte is then taken up into the fallopian tube via the fimbriae, ready to be fertilised
• If no fertilisation occurs, the 2^o oocyte degenerates 24 hrs after ovulation, remaining arrested in meiosis II. However, if fertilisation does take place, the 2^o oocyte completes meiosis II to form a haploid ovum and a 3rd polar body (which later disintegrates)
• The Graafian follicle becomes the corpus lutuem. The corpus lutuem is maintained for the first 16 weeks of pregnancy by the hormone Human Chorionic Gonadotropin (hCG) as it secretes progesterone that maintains the endometrium for implantation
• The endometrium will eventually become part of the placenta

Question 25

How many ovum and polar bodies are produced if fertilisation takes place?

Answer 25

1 ovum and 3 polar bodies

Question 26

How many polar bodies are produced if fertilisation does NOT take place?

Answer 26

2 polar bodies

Question 27

Give 5 differences between spermatogenesis and oogenesis

Answer 27

See table attached!

Question 28

What physiological changes are made to the sperm and the ovum so that the two can fertilise?

Answer 28

**_Sperm_** In order for sperm to penetrate the oocyte, it has to undergo **_capacitation_**, which involves: * **_Acrosomal reaction_** (see image) - where the membrane surrounding the acrosome fuses with the plasma membrane of the sperm's head, exposing the contents of the acrosome. The contents include surface antigens necessary for binding to egg's cell membrane, and numerous **_enzymes that are responsible for breaking through the egg's tough coating (zona pellucida)_** and allowing fertilisation to occur (fusion of the nucleus of the sperm and ovum). * Changing the tail movement from a beat-like action to a thrashing whip-like action to help propel the sperm forward. Ovum: * Contains cell surface glycoproteins called **_ZP3 proteins_**. They interact with the capacitated sperm and allow the acrosomal enzymes to be released from the acrosome. The acrosomal enzymes break down the zona pellucida, allowing the sperm nucleus to fuse with the ovum nucleus

Question 29

What are the changes made to the ovum following fertilisation to prevent polyspermy?

Answer 29

Penetration of the zona pellucida allows the sperm and oocyte cell membranes to fuse together. Ca2+ enters the oocyte and the sperm cell stops moving. **_The rise in intracellular Ca2+ results in 3 changes_**: 1. The egg cell membrane depolarises in order to prevent polyspermy - **_primary block_** 2. The **_cortical reaction_** occurs, which is where cortical granules that lie just beneath the egg cell membrane fuse with the membrane and release their contents into the zona pellucida. This is a **_secondary block_** to polyspermy as it hardens the zona pellucida 3. The egg **_completes meiosis II_**. Following fertilisation the zygote undergoes several changes which will **_result in the implantation within the wall of the uterus_**

Question 30

The development of reproductive organs is closely linked throughout with the development of the urinary system. Which mesoderm gives rise to both the embryonic kidney and the gonad?

Answer 30

Intermediate mesoderm

Question 31

Describe the **_indifferent stage_** in the embryonic development of male and female gonads

Answer 31

* At first, the **_intermediate mesoderm_** gives rise to a pair of **_urogenital ridges_**, one on each side. They initially do not contain any germ cells * **_In the 4th week, primordial germ cells (PGCs) begin to migrate from the yolk sac along the dorsal mesentery of the hindgut to the urogenital ridges in the retroperitoneum_**. They reach the urogenital ridges by the 6th week * Primitive sex cords are formed within the urogenital ridges, and together with PGCs they form an **_indifferent gonad_** meaning that **_it's the same primordial gonad regardless of XX or XY_**

Question 32

Describe how an indifferent gonad develop into a male gonad

Answer 32

In a male embryo, the XY sex chromosomes are present. The Y-chromosome contains the **_SRY gene_** that stimulates the development of the primitive \*sex cords (medullary cords) to become the testis cords. The thick tunica albuginea forms around the cords * A portion of the testis cords breaks off to form the future rete testis * The remaining cords contain 2 types of cells: * **_Germ cells_** (spermatogonia, spermatocytes, spermatids, spermatozoa) * **_Sertoli cells_** * These 2 types of cells together form the **_germinal epithelium_** * In puberty, these cords **_acquire a lumen_** and **_become the seminiferous tubules_**, the **_site of spermatogenesis_** * Located between (or just outside) the testis cords are the **_Leydig cells_** (derived from intermediate mesoderm). In the 8th week, they begin producing testosterone which drives differentiation of the internal and external genitalia \*Sex cords are structures that develop from the urogenital ridges

Question 33

Please see the image attached for the illustration of the anatomies described in the embryonic development of testes

Answer 33

See image! The image on the right shows the cross-section of the seminiferous tubules, you can clearly see a lumen in the centre of the seminiferous tubules. The lumen is where spermatozoa leave the germinal epithelium. The sperm then travel through the seminiferous tubules into the rete testis and then the ductili efferentes before being stored in the epididymis until ejaculation Before males reach puberty, the seminiferous tubules don't have a lumen yet, but once they reach puberty, they acquire a lumen! You can also see that leydig cells are lying just outside the seminiferous tubules

Question 34

Describe how an indifferent gonad differentiates into a female gonad

Answer 34

In a female embryo, the XX sex chromosomes are present. As there is no Y chromosome, there is **_no SRY gene_** to influence develpoment. Without it, **_the primitive sex cords degenerate_** and **_do not form the testis cords_** Instead, the surface epithelium of the gonad continues to proliferate, producing **_cortical cords_** (also called secondary cords). In the 3rd month, these cords break up into clusters, surrounding each oogonium with a layer of **_epithelial follicular cells_**, forming a **_primordial follicle (or primary follicle)_**

Question 35

Describe how internal genitalia develop for males and females?

Answer 35

* In the first weeks of urogenital development, all embryos have 2 pairs of ducts, one on each side, both draining into the urogenital sinus part of the cloaca. These are the: * Mesonephric (Wolffian) ducts * Paramesonephric (Mullerian) ducts * The fate of these ducts depends on whether there is a functional testis * **Male** * In the presence of **_testosterone_** (produced by the Leydig cells), the mesonephric ducts remain and develop to form the **_efferent ductules_**, **_epididymus_**, **_vas deferens_** and **_seminal vesicles_** * The **_Sertoli cells_** of the testes produce **_Mullerian-inhibiting hormone (MIH_**) which **_inhibits Mullerian (paramesonephric) ducts development_**, so they **_degenerate_** * **_​_**Its developmental remnant is the appendix testis (also called Hydatid of Morgagni), a small portion of tissue located on the upper pole of each testicle, which has no function at all * **Female** * In females, there are no Leydig cells to produce testosterone. **_In the absence of this hormone, the mesonephric ducts degenerate_**, leaving behind only a vestigial remnant called the Gartner's duct * Lack of MIH allows the Mullerian (paramesonephric) ducts to remain and develop. These ducts have 3 parts: * Cranial - becomes the Fallopian tubes * Horizontal - becomes the Fallopian tubes * **_Caudal - fuses to form the uterus, cervix and the upper 1/3rd of the vagina_** * The lower 2/3rd of the vagina is formed by the sinovaginal bulbs (derived from the pelvic part of the urogenital sinus - hindgut endoderm)

Question 36

What is the other function of the mesonephric ducts in both male and female embryoes?

Answer 36

The mesonephric duct in both male and female embryoes initially develops as a duct that drain urine from the embryonic kidney (metanephros) to the urogenital sinus. The upper part of the UG sinus becomes the bladder and the lower part becomes the pelvic urethra Once the embryonic kidney becomes a fully functional adult kidney at around 28 days, it takes over the production of urine (the urine is drained to the UG sinus through a metanephric duct), so the mesonephric duct degenerates. However, if you are a male, the mesonephric duct is maintained by testosterone and thus converted into the vas deferens and the epididymis, which then descend with the testis into the scrotum through the inguinal canal. If you are a female, it degenerates in the absence of androgens

Question 37

If there is a lack of fusion of the paramesonephric ducts, what uterine defects can it potentially cause?

Answer 37

The most common uterine defect is bicornuate uterus where there are 2 uteruses sharing a common single vagina. As it's asymptomatic, the condition is often only picked up on an USS during pregnancy. It's associated with a high risk of **_miscarriage_** and **_premature delivery_** Other uterine defects are shown in the image attached

Question 38

Describe the development of external genitalia in males and females

Answer 38

Indifferent stage * The development of the external genitalia begins in the 3rd week * Initially, the external genitalia is indifferent with 3 basic components: * **_Genital tubercle_** * **_Genital folds_** - urethral folds (anterior) + anal folds (posterior) * **_Genital swellings_** on either side of the urethral folds * They then develop differently after this stage and this depends on whether or not dihydrotestosterone is produced * In male embryoes, the production of DHT causes * **_Rapid elongation of the genital tubercle --\> phallus_** * **_Anteriorly, the urethral folds fuse to form urethral groove_** - the folds close over by the 4th month, forming the penile urethra * **_Genital swellings --\> scrotal swellings_** (moving caudally to eventually form the scrotum) * In female embryoes, this is driven by oestrogens * The **_genital tubercle_** only elongates slightly to form the **_clitoris_** * The **_urethral folds_** do not fuse, creating the **_vaginal orifice_** and **_labia minora_** * **_Genital swellings_** form the **_labia majora_**

Question 39

What is the name of condition called where there are one or more abnormal openings of the urethra along the **_inferior side_** of the penis?

Answer 39

**_Hypospadias_** - due to incomplete closure of the urethral folds during development. Very common (around 1 in 300 births) Surgery is needed to correct this defect

Question 40

Describe how gonads descend into position (scrotum for male and true pelvis for female) from the abdomen

Answer 40

Male * **_Descent of testes starts at around 28th week and they reach the scrotum by the 33rd week_** * The testes are attached to the gubernaculum which facilitates its descent down through the inguinal canal towards the scrotal swelling. The peritoneum folds (processus vaginalis) allowing the testis to descend further into the scrotum. This processus vaginalis later closes and becomes the tunica vaginalis surrounding the testes in adult life Female * The gubernaculum attaches the ovary to the labia majora and the ovary descends until it’s stopped at the pelvis by the developing uterus. The round ligament descends through the inguinal canal * The gubernaculum becomes the ovarian ligament and the round ligament of the uterus

Question 41

Give 4 complications of undescended testis

Answer 41

Testicular cancer Testicular torsion Infertility Psychological complication

Question 42

An 8-week-old boy is brought to see his GP as his parents are worried that one of his testes remains undescended. His parents report an uncomplicated pregnancy and birth, with the patient being born at term. He has been well since birth. Examination reveals that the left testicle is absent from the scrotal sac, unretractile and impalpable in the abdomen. The right testicle has fully descended. Based on the above information, what is the most appropriate next stage in this patient's management? a) . Reassurance without further follow-up b) . Routine referral to paediatric surgey c) . Urgent referral to paediatric surgery d) . Review at 1 yrs of age e) . Review in 1 month

Answer 42

The answer is a - review in 1 month **_CKS recommends that referral should be considered from 3 months of age_**. This baby is only 8 weeks old so you should review him in a month to see if the testis remains undescended. If it is, then you refer the baby, with the baby ideally seeing a urological surgeon before 6 months of age **_Orchidopexy is usually performed at 1 yr of age_**

Question 43

How do you manage bilateral undescended testes?

Answer 43

They should be reviewed (**_urgent referral_**) by a senior paediatrician **_within 24 hrs_** as the child needs urgent endocrine or genetic Ix to rule out **_congenital adrenal hyperplasia_** or **_androgen insensitivity syndrome_**!