Reproductive System Week 1 Flashcards
Which chromosome is the key to sexual dimorphism?
The Y chromosome
Which gene on the Y chromosome is responsible for male development?
SRY (Sex-determining region on Y) gene on Yp11
Which protein is produced from SRY and what is its function?
Testis-determining factor - transcription factor initiating a cascade of downstream genes that cause male development
In what week of development do the gonads acquire male or female characteristics?
Week 7
How do the gonads initially appear in the embryo?
As a pair of longitudinal ridges - ‘genital or gonadal ridges’
How are the genital ridges formed?
By proliferation of the epithelium and a condensation of the underlying mesenchyme
In what week of development do germ cells appear in the genital ridges?
Week 6
Describe the journey of the primordial germ cells to the genital ridges
Originate in the epiblast
Migrate through the primitive streak
By week 3 reside among endoderm cells in the wall of the yolk sac, close to the allantois
In 4th week migrate by ameboid movement along the dorsal mesentery of the hindgut
Arrive at the primitive gonads at the beginning of the 5th week
Invade the genital ridges in the 6th week
How do the germ cells affect the development of the gonads?
If they fail to reach the ridges, the gonads do not develop
They have an inductive influence on the development of the gonad into ovary or testis
Describe the development of the primitive sex cords
Shortly before and during arrival of the primordial germ cells, the epithelium of the genital ridge proliferates and epithelial cells penetrate the underlying mesenchyme
Here they form a number of irregularly shaped cords
These cords are connected to surface epithelium in both female and male embryos
Is it possible to differentiate between the male and female gonad in this early stage?
No
They are known as the indifferent gonads
What sex chromosomes are carried in the primordial germ cells of an embryo that is genetically male?
XY (can have multiple X)
What sex chromosomes are carried in the primordial germ cells of an embryo that is genetically female
XX (no Y)
What effect does testis-determining factor have on the primitive gonads?
The primitive sex cords continue to proliferate and penetrate deep into the medulla to form the testis/medullary cords
What happens towards the hilum of the gland?
The cords break up into a network of tiny cell strands that later give rise to tubules of the rete testis
What is the tunica albuginea?
A dense layer of fibrous connective tissue that develops and separates the testis cords from the surface epithelium of the gonad
What happens to the testis cords in the 4th month of development?
The testis cords become horseshoe-shaped and their extremities are continuous with those of the rete testis
What are the testis cords composed of in the 4th month of development?
Primitive germ cells and sustentacular cells of Sertoli (from the surface epithelium of the gonad)
What are the names of the cells that lie between the testis cords?
Interstitial cells of Leydig
Where are the interstitial cells of Leydig derived from?
From the original mesenchyme of the gonadal/genital ridge
When do the interstitial cells of Leydig develop?
They begin development shortly after onset of differentiation of the testis cords (7th week)
What do the interstitial cells of Leydig produce and what is the consequence of its production?
Testosterone
Influences the sexual differentiation of the genital ducts and external genitalia
What happens to the testis cords during puberty?
They acquire a lumen, forming the seminiferous tubules
Describe the structures you would pass through when travelling from the seminiferous tubules to the ductus deferens
Seminiferous tubules
Rete testis tubules
Ductuli efferentes
Ductus deferens
From what do the ductuli efferentes develop?
The excretory components of the mesonephric system
From what did the ductus deferens differentiate?
The mesonephric or Wolffian duct
What is the fate of the primitive sex cords in the female embryo?
They dissociate into irregular cell clusters, containing groups of primitive germ cells and occupying the medullary part of the ovary
Later replaced by vascular stroma/connective tissue that forms the ovarian medulla
What is different about the surface epithelium of the female gonad compared to the male gonad?
It continues to proliferate and in the 7th week gives rise to cortical cords, which penetrate the underlying mesenchyme but remain close to the surface
Describe the fate of the cortical cords
In the 3rd month the cords split into isolate cell clusters
Cells in these clusters proliferate
They surround each oogonium with a layer of epithelial cells - “follicular cells”
What constitutes a primordial follicle?
The oogonium and surrounding follicular cells
What is the indifferent stage with respect to the genital ducts?
Both male and female embryos start with two pairs of genital ducts: mesonephric (Wolffian) ducts and paramesonephric (Mullerian) ducts
Describe the paramesonephric duct
Arises as a longitudinal invagination of the epithelium on the anterolateral surface of the urogenital ridge
Cranially the duct opens into the abdominal cavity with a funnel-like structure
Caudally it runs lateral to the mesonephric duct, crosses ventrally to grow caudomedially
Comes into contact with the paramesonephric duct from the opposite side in the midline
The caudal tip of the combined ducts projects into the posterior wall of the urogenital sinus
Causes a small swelling - sinus tubercle
Where do the mesonephric ducts open into?
The urogenital sinus on either side of the sinus tubercle
What effect does testosterone have on the genital ducts?
The epigenital tubules (the excretory tubules of the mesonephros) contact the rete testis and form the efferent ductules
The excretory tubules at the pole of testis (paragenital tubules) do not join the rete testis - become a remnant known as paradidymis
The mesonephric duct persists (apart from appendix epididymis) and forms the main genital duct
Immediately below the efferent ductules the mesonephric duct elongates and becomes highly convoluted forming the ductus epididymis
Between the epididymis and the outbidding of the duct (seminal vesicle) obtains a thick muscular coat - forming ductus deferens
Region of the duct beyond seminal vesicle - ejaculatory duct
What hormone is produced by Sertoli cells and what is its action?
Anti-mullerian hormone or Mullerian inhibiting substance
Causes the paramesonephric ducts to degenerate except for the small portion at the cranial ends (appendix testis)
What causes the paramesonephric duct to become the main genital duct of the female?
The presence of oestrogen and the absence of testosterone and MIS(AMH)
Describe what happens to the paramesonephric duct in the female
With descent of the ovary:
The cranial and horizontal portions develop into the uterine tube
The caudal parts fuse to form the uterine canal
Describe the formation of the broad ligament of the uterus
As the horizontal part of the paramesonephric duct moves mediocaudally, the urogenital ridges come to lie in a transverse plane
After the ducts fuse in the midline a broad transverse pelvic fold is established
Extends from the lateral sides of the fused paramesonephric ducts toward the wall of the pelvis
How is the pelvic cavity divided in the female?
The uterus and broad ligaments divide the cavity into the uterorectal pouch and the uterovesical pouch
What structures do the fused paramesonephric ducts give rise to?
The corpus and cervix of the uterus
And the upper portion of the vagina
What structures of the uterus are formed from mesenchyme?
The myometrium and the perimetrium
What is the consequence of the absence of testosterone in females?
The mesonephric ducts degenerate
In what week of development does the uterine septum disappear?
Week 9
What is the name of the two solid evaginations that grow out from the pelvic part of the sinus shortly after the sinus tubercle is formed?
The sinovaginal bulbs
Describe the fate of the sinovaginal bulbs
They proliferate and form a solid vaginal plate
Proliferation continues at the cranial end - increasing the distance between the uterus and the urogenital sinus
By what month is the vaginal outgrowth entirely canalised?
5th month
What is the name of the wing-like expansions of the vagina that surround the end of the uterus and what is their origin?
Vaginal fornices
Paramesonephric origin
What is the embryonic origin of the vagina?
Has a dual origin :
- upper portion (vaginal fornices) are paramesonephric
- lower portion is derived from urogenital sinus
What separates the lumen of the vagina from the urogenital sinus?
A thin layer of tissue consisting of a thin layer of vaginal cells and the epithelial lining of the sinus - the hymen
Usually develops an opening during perinatal life
What are the names of the remnants of the cranial and caudal excretory tubules found in the mesovarium?
Epoophoron
Paroophoron
Does the entirety of the mesonephric duct disappear?
A small cranial portion can be found in the epoophoron and occasionally a small caudal portion may be found in the wall of the uterus or vagina
What is the consequence of the small caudal remnant of the mesonephric duct that may be found on the wall of the uterus or vagina?
Later in life may form Gartner cyst
What is the pathophysiology behind duplications of the uterus and what are the names of these conditions?
Lack of fusion of the paramesonephric ducts:
In a local area:
- Uterus bicornis (relatively common - uterus has two horns entering common vagina)
- Uterus arcuatus (least severe - slight indentation in middle)
Throughout their normal line of fusion:
- Uterus didelphys (entirely double with double vagina)
What are the consequences of and conditions associated with complete or partial atresia of one or both of the paramesonephric ducts?
One duct:
The rudimentary part lies as an appendage to the well-developed side
It’s lumen usually does not communicate with the vagina - complications are common
Uterus bicornis unicorns with one rudimentary horn
Two ducts:
Atresia of the cervix may result
If the sinovaginal bulbs fail to fuse - double vagina
If sinovaginal bulbs fail to develop - vaginal atresia with small vaginal pouch derived from paramesonephric ducts surrounding uterus
Describe the indifferent stage with respect to the external genitalia
3rd week of development
Mesenchyme cells originating in the primitive streak migrate around the cloacal membrane
Form a pair of slightly elevated cloacal folds
Cranial to cloacal membrane folds unite to form genital tubercle
Caudally the folds are subdivided to into urethral folds anteriorly and anal folds posteriorly
Genital swellings become visible on each side of the urethral folds
Cant distinguish the two sexes at the end of week 6
What is the consequence of androgen secretion for the external genitalia?
Rapid elongation of the genital tubercle - now called phallus
This pulls the urethral folds forward - so they form lateral walls of the urethral groove
The groove extends along the caudal phallus but does not reach the glans
Urethral plate formed from endoderm - epithelial lining of the groove
At the end of 3rd month - urethral folds close over the urethral plate forming the penile urethra (does not extend to phallus tip)
In the 4th month ectodermal cells from the tip of the glans penetrate inward and form a short epithelial cord - later obtains lumen and becomes external urethral meatus
The scrotal swellings arise in the inguinal regions and move caudally with development - each makes up half of the scrotum and they are separated by the scrotal septum
Describe the meaning of the term hypospadia
Fusion of the urethral folds is incomplete
Abnormal openings of the urethra occur along the inferior aspect of the penis - near the glans, along the shaft or near the base, rarely extends along scrotal raphe
When fusion of folds fails entirely - wide sagittal slit along entire length of penis and scrotum - scrotal swellings resemble labia majora
Incidence of 3-5/1000 births
Doubled over the past 15-20 years
Potentially due to rise in environmental oestrogens
What is epispadia?
Rare abnormality (1/30000) Urethral meatus is found on dorsal of penis May occur as isolated defect Most often associated with exstrophy of the bladder and abnormal closure of the ventral body wall
What is a micro penis?
Occurs when insufficient androgen stimulation for external genitalia growth
Caused by primary hypogonadism or
hypothalamic or pituitary dysfunction
Penis is 2.5 standard deviations below the mean length as measured along the dorsal surface from the pubis to the tip with the penis stretched to resistance
When might bifid penis/double penis occur?
If the genital tubercle splits
What stimulates the development of female external genitalia?
Oestrogens
What is the fate of the genital tubercle in the female?
Elongates only slightly, forming the clitoris
What is the fate of the urethral folds in the female?
Do not fuse
Develop into labia minora
What is the fate of the genital swellings in the female?
Enlarge and form the labia majora
What does the urogenital groove form in the female?
Remains open and forms the vestibule
Why cant we use genital tubercle length to determine the sex of a foetus during the early stages of development (3rd and 4th month)?
The female genital tubercle is longer than the male genital tubercle in the early stages of development
Where do the testes develop and how do they reach the scrotum?
They develop retroperitoneally in the abdomen and move caudally, passing through the abdominal wall to reach the scrotum
How do the testes pass through the abdominal wall?
Through the inguinal canal
Briefly describe the inguinal canal
Lies just superiorly to medial half of inguinal ligament
4cm long
Entry via the deep inguinal ring
Exit via the superficial inguinal ring near the pubic tubercle
Which two structures extend from the caudal pole of the testis?
Caudal genital ligament (ligamentous remnant of the urogenital mesentery)
Gubernaculum (mesenchymal condensation rich in extracellular matrices)
Describe briefly how the descent of the testes occurs
Prior to descent gubernaculum terminates in inguinal region between external and internal abdominal oblique muscles
As testes descend towards inguinal ring extra abdominal portion of gubernaculum forms
Grows from inguinal region toward scrotal swellings, produces intraabdominal migration of testes
Increase in intra abdominal pressure due to organ growth causes testis to pass through inguinal canal the extra-abdominal gubernaculum contacts scrotal floor
Regression of extra-abdominal gubernaculum completes movement of testis into scrotum
By what week of development do the testis reach the scrotum?
33 weeks
By what week do the testis reach the inguinal region?
12 weeks
Which hormones influence the descent of the testes?
Androgens and MIS
How is blood supplied to the testes?
Blood supply from the aorta is retained - testicular vessels extend from original lumbar position to the testis in the scrotum
What is the name given to the evagination of peritoneum that follows the gubernaculum into the scrotal swellings?
Processes vaginalis
How is the inguinal canal formed?
The processus vaginalis accompanied by the muscular and fascial layers of the body wall evagination into the scrotal swelling
Are the testes present in the scrotum at birth?
Yes
What is left covering the testes after obliteration of the narrow canal connecting the processus vaginalis to the peritoneal cavity?
The tunica vaginalis
When is the connection to the peritoneal cavity obliterated?
At birth or shortly after
What are the layers surrounding the testes and from which abdominal layer are they derived?
Internal spermatic fascia - from transversalis fascia
Cremasteric fascia and muscle - from the internal abdominal oblique muscle
External spermatic fascia - from the external abdominal oblique muscle
Describe the descent of the ovaries
Dont travel very far compared to testes
Settle just below the rim of the true pelvis
What does the cranial genital ligament form in the female
The suspensory ligament of the ovary
What does the caudal genital ligament form in the female?
The ligament of the ovary proper and the round ligament of the uterus
Do females have a gubernaculum?
Yes
In normal cases it remains rudimentary
Does anything travel through the inguinal canal in female?
Yes
The round ligament travels through the inguinal canal to the labia majora
Describe ambiguous genitalia?
May appear as a large clitoris or a small penis
What is a hermaphrodite?
An individual with typically female, typically male or ambiguous genitalia, characteristics of both sexes, ovotestes (have both testicular and ovarian tissue)
In 70% cases 46XX - usually a uterus - external genitalia are ambiguous or predominantly female and most of these individuals are raised female
What is the most common cause of genital ambiguity?
Congenital adrenal hyperplasia
Genotype doesnt match phenotype
Decreased steroid hormone production
Increase in ACTH production
21-hydroxylation inhibited
Females - partial masculinisation with large clitoris, to virilisation and a male appearance, rare form of CAH 17a-hydroxylase deficiency results in female internal and external anatomy at birth but failure of secondary sex characteristics
Males - with 17a-hydroxylase deficiency - virilisation inhibited
What is Androgen insensitivity syndrome?
Males lacking androgen receptors or failure of tissue to respond to receptor-dihydrotestosterone complexes
Male genitalia do not develop but because they have testes and MIS is present the female duct system and genitalia is also absent
Complete androgen insensitivity syndrome - vagina present but poorly developed - testes in labial or inguinal regions - spermatogenesis doesnt occur - increased risk of testicular tumours - 33% develop malignancies prior to age 50
Mild androgen insensitivity syndrome - there is virilisation to some degrees
Partial androgen insensitivity syndrome - ambiguous genitalia, testes usually undescended
What is 5-a-reductase deficiency?
Causes ambiguous genitalia in males
Inability to convert testosterone to dihydrotestosterone due to lack of reductase enzyme
External genitalia do not develop normally
May appear male but underdeveloped or female with clitoromegaly
What is Klinefelter syndrome?
47XXY (or XXXY) Most common sex chromosome disorder 1/1000 males Decreased fertility Small testes Decreased testosterone levels Gynecomastia in 33% of individuals Nondisjunction of the XX homologues is the most common cause
What is gonadal dysgenesis?
Oocytes are absent
Ovaries appear as streak gonads
Individuals phenotypically female
May have variety of chromosomal complements:
Sawyer syndrome (XY female gonadal dysgenesis) - point mutations or deletions of SRY gene - individuals appear as normal females but do not menstruate or develop secondary sex characteristics at puberty
Turner syndrome (45X) - short stature, high-arched palate, webbed neck, shield-like chest, cardiac and renal anomalies, inverted nipples
What may occur as a consequence of a persistent connection between the peritoneal cavity and the processus vaginalis ?
Intestine loops can descend into scrotum - congenital indirect inguinal hernia
What is the consequence if the obliteration of the passageway between the peritoneal cavity and the processus vaginalis is irregular, leaving small cysts along its course?
These cysts may secrete fluid forming a hydrocoele of the testis and/or spermatic cord
If the testes arent in the scrotum at birth when would you expect them to have descended by?
Should be completed during the first 3 months postnatal
What is cryptorchidism?
The failure of one or both testes to descend (1% of infants)
Decreased androgen production may cause it
Undescended testes fail to produce mature spermatozoa
Associated with 3-5% incidence of renal anomalies
Describe gametogenesis
Germ cells proliferate by mitosis
Reshuffle genetically and reduce to haploid cells by meiosis
Cytodifferentiate into mature gametes
Time scale varies between sexes
Describe the frequency and amount of ova produced
Very few gametes (~400 in lifetime)
Intermittent production (~1 a month)
~1/400th of reproductive potential (e.g. Only one used)
Describe the frequency and amount of sperm production
Huge number (~200 million/day)
Continuous production
Essentially disposable cells
What are the major functions of meiosis?
Reduce the chromosome number to 23 in each gamete (haploid)
Ensure every gamete is genetically unique
When is meiosis used in the body?
Only in the production of gametes
Genetic variation arises from:
Crossing over Independent assortment (the homologues go in different directions) Random segregation (the way they line up is random)
Describe spermatogenesis
Spermatogonia (germ cells) are the raw material
Available for up to 70 years
Divide by mitosis giving rise to Ad spermatogonia (maintain stock) and Ap spermatogonia (become primary spermatocytes)
Primary spermatocytes divide by meiosis I to secondary spermatocytes and meiosis II into spermatids (4 haploid spermatids per primary spermatocyte)
Spermatids differentiate into spermatozoa by spermiogenesis
Define the spermatogenic cycle
Since not all stages of spermatogenesis are visible in a single cross-section of seminiferous tubule and cells appear in groups with same maturation stages
The cycle is defined as the time taken for the reappearance of the same stage within a given segment of tubule (~16 days in human)
Define the spermatogenic wave
Different stages of spermatogenesis are ordered in time as well as space
And each stage follows in an orderly sequence along the length of the tubule
A wave is defined as the distance between the same stage
They move in spirals towards the inner part of the lumen
What is spermiation?
The release of spermatids into the seminiferous tubules
What is spermiogenesis?
The spermiation and the remodelling of spermatids to spermatozoa as they are transported by Sertoli cell secretions and peristaltic contractions to the epidymidis
When do spermatozoa become motile?
In the epidymidis
How much semen is typically produced per ejaculate?
2ml
Describe the contents of semen
Seminal vesicle secretions (70%) - amino acids, citrate, fructose, prostaglandins
Secretions of prostate (25%) - proteolytic enzymes, zinc
Sperm (via vas deferens) (2-5%) - 200-500 million per ejaculate
Bulbourethral gland/ Cowper gland secretions (<1%)- mucoproteins (lubricate and neutralise acid urine in distal urethra)
What is the final step required for sperm to become fertile?
Capacitation
Where does capacitation occur
Female genital tract
What happens to sperm during capacitation
Removal of glycoproteins and cholesterol from sperm membrane
Activation of sperm signalling pathways (atypical soluble adenylyl cyclase and PKA)
Allows sperm to bind to zona pellucida of oocyte and initiate acrosome reaction
How do sperm become fertilised for in vitro purposes?
Incubated in capacitation media
Do females produce any potential gametes after birth?
No the entire stock of potential gametes are developed before birth
What is the menopause and at what age does it typically occur?
The stage when 0% of the non growing follicle population are remaining
Typically occurs ~50-55 years of age
When does oogenesis begin?
Before birth
Describe oogenesis before birth
Oogonia proliferate rapidly by mitosis
By end of 3rd month oogonia arranged in clusters surrounded by flat epithelial cells
Majority continue to divide by mitosis
Some enter meiosis and arrest in prophase of meiosis I - called primary oocytes
Reach a max number of ~7 million cells
Then many oogonia and primary oocytes degenerate by atresia
By 7th month the majority of oogonia have degenerated
All survivors (~2 million) have now entered meiosis I and are individually surrounded by flat layer of epithelial cells called follicular cells - primordial follicle
How many oocytes remain at puberty?
~40,000
How many oocytes pass mature each month following puberty?
~15-20
Describe the preantral stage
Primordial follicles continue to grow
Follicular cells change from flat to cuboidal and proliferate to produce a stratified epithelium - granulosa cells
What is secreted by the granulosa cells?
A layer of glycoprotein onto the oocyte - forming zona pellucida
Describe the antral stage
Fluid filled spaces appear between granulosa cells and coalesce to form the antrum
Forms the secondary follicle
How many oocytes reach maturity?
Several follicles develop with each ovarian cycle
Usually only one reaches maturity (rest atretic)
What is the cumulus oophorus?
The layer of granular cells surrounding the oocyte
Which hormone induces the preovulatory phase?
Luteinising hormone
Describe the preovulatory phase
Meiosis I is complete resulting in two haploid daughter cells of different sizes
One cell receives most of the cytoplasm
The other cell is known as the first polar body
Cell enters meiosis II but arrests in metaphase (3 hours before ovulation)
Meiosis II only completes if cell fertilised otherwise degenerates 24 hours after ovulation
Which hormones stimulate rapid growth of follicule several days before ovulation?
Luteinising hormone
Follicle stimulating hormone
Describe ovulation
LH and FSH stimulate follicle growth several days before ovulation
Mature follicle ~2.5cm diameter - called Graafian follicle
LH increases collagenase activity
Prostaglandins increase response to LH and cause local muscle contractions in ovarian wall
Oocyte extruded - breaks free from ovary
What is the corpus luteum and what is its function?
The remaining granulosa cells and theca interna cells that have become vascularised, developed a yellow pigment and become lutein cells
Secretes oestrogen and progesterone
Which stimulate uterine mucosa to enter secretory stage in preparation for embryo implantation
Dies after 14 days if no fertilisation
How is the oocyte transported along the uterine tube?
Shortly before ovulation fimbrae sweep over surface of ovary and cilia on epithelial lining move oocyte out of ovary into tube
Uterine peristaltic contractions and cilia propel the oocyte towards the uterus
Reaches the uterine lumen in 3-4 days if fertilised
What happens to the corpus luteum if fertilisation does not occur?
Degenerates, forming the corpus albicans (mass of fibrotic scar tissue)
Therefore progesterone production decreases, causing menstrual bleeding
What happens to the corpus luteum if fertilisation occurs?
Degeneration of the CL prevented by human chorionic gonadotropin secreted by developing embryo
Corpus luteum continues to grow forming the corpus luteum graviditatis
Cells of CLG continue to secrete progesterone until 4th month when placental secretion replaces it
Where are FSH and LH released from?
Anterior pituitary gland
What stimulates the release of LH and FSH?
GnRH (from hypothalamus)
How many polar bodies are formed in oogenesis?
3
Outline some differences between spermatogenesis and oogenesis
Spermatogenesis:
~ 200 million sperm a day
4 spermatids formed with no polar body formation and equal division of cytoplasm
Starts at puberty
Continues throughout adult life
Motile gametes
All stages of division complete in testes
Oogenesis:
Usually 1 ovum per 28 day menstrual cycle
One ovum with unequal cytoplasm division and 3 polar bodies formed
Starts in foetus
Finishes at menopause
Non-motile gametes
Last stage of meiosis 2 occurs in oviduct upon fertilisation
What tissue forms the matrix of the gonads into which the primordial germ cells migrate?
Somatic mesoderm
Which reproductive hormones are released from the hypothalamus?
Gonadotropin releasing hormone
Prolactin releasing hormone
Prolactin inhibiting hormone
Which reproductive hormone is released from the posterior pituitary gland?
Oxytocin
Which reproductive hormones are released from the anterior pituitary gland?
Follicle stimulating hormone
Luteinising hormone
Prolactin
Which reproductive hormones are released from the gonads?
Male - testosterone
Female - oestrogens (oestradiol, oestrone, oestriol) and progesterone
Inhibin
Which reproductive hormones are released from the placenta?
Human chorionic gonadotropin
Human placental lactogen
Oestrogens and progesterone
What are the names of the outer fibrous layer and inner secretory layer of cells surrounding the granulosa cells?
Theca externa - outer fibrous layer
Theca interna - inner secretory layer
List some male secondary sexual characteristics
Appearance of pubic, axillary and facial hair
Enhanced growth of the chest
Deepening of the voice
Skin thickens and becomes oily
Bones grow and increase in density
Skeletal muscles increase in size and mass
List some female secondary sexual characteristics
Widening of the hips Softer and smoother skin Breast development Growth of pubic and axillary hair Beginning of menstruation Changes in quantity and distribution of subcutaneous fat (energy stores for pregnancy)
