Gametogenesis And Reproductive Embroyology Flashcards
Difference between genetic/gonadal and phenotypic sex
Genetic = determined at conception
- XX or XY
Gonadal = established during the 7th week of gestation based on absence or presence fo functional SRY gene
- the SRY gene is on the Y-chromosome and encodes for the Testis-determine factor (TDF). It’s presence in week 7 induces indifferent gonads into testies by inhibiting signaling factors for ovaries
Phenotypic = affected by expression of certain hormones during development
(Testosterone/MIF/DHT)
Hormones that affect sexual differentiation during gestation
Testosterone
- expression occurs in 8th week
- stimulates development of the vas deferens/seminal vesicles and epididymis
MIF
- expression occurs in the 8th week
- inhibits development of the uterus, Fallopian tubes, cervix and upper vagina
DHT
- expression occurs in 9-12th weeks
- stimulates development of the prostate, penis and scrotum
Androgenic hormones vs estrogen in embryology
Androgenic hormones
- testosterone and dihydrotestosterone
- promotes growth and differentiation of the male reproductive tract from the mesonephric duct and external genitalia
- produces anti mullarian hormone which inhibits growth and differentiation of the paramesonephric duct (female reproductive tract)
Estrogen
- produced by ovaries after week 8 which promotes the growth and differentiate of the female reproductive tract and external genitalia
- estrogen inhibits mesonephric duct formation
Gametogenesis 4 phases
1) origin and migration of primordial germ cells to the genital ridge
2) increase in number of germ cells occurs via rapid mitosis once the primordial germ cells reach the gonadal/genital ridge
- turns into millions and this period varies slightly between females and males
- females = induces oogonia proliferation during the 2nd-5th month of pregnancy
- males = induces spermatogonia in the 2nd trimester. Then ceases and resumes once puberty is reached
3) meiosis occurs and produces gametes
3 types of gonadal ridge cell types
1) mesenchymal cells
- makes up the gonadal ridge medulla
- in males = leydig cells
- in females = ovarian support stroma
2) mesothelial cells
- make up the gonadal ridge cortex
- males = seminiferous tubules
- females = ovarian follicles
3) primordial germ cells
- future gamete cells
- males = makes sperm
- females = makes oogonia
Meiosis 1
Similar to mitosis except
- prophase 1 synapses occurs and crossover occurs
Phases
1) prophase 1: chromosomes condense and the nuclear envelope breaks down and cross over occurs
2) metaphase 1: pairs of homologous chromosomes move to the equator of the cell and line up
3) anaphase 1: homologous chromosomes move to opposite poles of the cell
4) telophase 1 and cytokinesis: chromosomes gather at poles and the cytoplasm divides
- ends up with 2 haploid 2N cells
Meiosis 2 is the same meiosis 1 except chromosomes dont replicate and result in 4 haploid 1N cells
How does meiosis differ between females and males
Males = each round produces 4 viable haploid spermatids
Females = each round produces 1 viable haploid oocyte with 3 polar bodies forming (arrested oocyte)
How does oogenesis occur before birth and during puberty
Before birth:
- Meiosis occurs but arrests a primary oocyte in prophase-1
- is surrounded by a perimordial follicle at this time
Puberty and on
- meiosis of a primary oocyte occurs and arrests in metaphase 2 as a secondary oocyte
- generates a polar body each time primary -> secondary
- will move from metaphase 2 if a the fertile oocyte is penetrated by sperm
- gets released from the follicle during ovulation
Spermatogenesis
Begins at puberty (not before)
A spermatogonium (46,XY) is released and divided into secondary spermatocytes (23,X and Y) and eventually 4 spermatids (23,X/X/Y/Y)
46,XY disorders of sex development (DSD)
Include
- androgen insensitivity
- low androgen production
- LH/hCG receptor depletion
- pure or partial gonadal dysgenesis
- ovotesticular
- testis regression
Sex chromosome DSD’s
Include 45,XO (Turner syndrome) 47,XXY (Klinefelter syndrome) 45,XO/46,XY (mixed gonadal dysgenesis) 46, XX/46,XY (ovotesticular DSD)
46,XX DSDs
Include
- androgen excess in females (fetal/maternal or placental)
- gonadal dysgenesis
- ovotesticular development
Androgen insensitivity syndrome
Testicular femininization syndrome
X-linked recessive mutation that produces a 46,XY chromosome (genetically male) who has a resistance to testosterone at the cellular level (kinda like DM type 2 but for testosterone)
- there are mutations in cellular androgen receptors
Will produce female external genitalia with a vagina that has a blind end pouch
- no uterus or uterine tubes will be present
- will produce breasts and female sex characteristics at birth
The testes will underdeveloped and usually reside in the inguinal canal, abdomen or labia majora (they are also cryptochidism testies)
Lab results
- before puberty = high testosterone
- after puberty = high estrogen and LH with high testosterone
- genetic testing confirms
Treatment
- estrogen replacement for complete androgen insensitivity
- if partial and wants to be male (gender identity) then can give high dose androgen therapy
- either way, also need to do a gonadectomy after puberty to prevent malignancy
46,XX DSD
“Female pseudohermaphroditism”
Patient is 46,XX at birth (genetically female)
However they typically present with some sort of disorder (CAH/21-hydroxylase is the most common) that causes a production of androgens in utero
Produces external genitalia that are male but also have a upper vagina, uterus and uterine tubes all of which technically work since the ovaries are also present and fertile
Cryptochidism
Refers to a condition that results in failure of testes to descend into the scrotum
Most common birth defect in neonate males (up to 30% chance)**
If the testicles don’t descend by year 5 = sterility
Also shows high risk for germ cell tumors
Epispadias and hypospadias
Epispadias
- embryonic malformation due to incomplete urethral tubular action on the dorsal penis
- can be by itself but heavily associated with exstrophy of the bladder
Hypospadias
- embryonic malformation that develops due to failure of the urethral folds and for skin to fuse on ventral penis
- results from inadequate production fo androgens from testies
- 4 subtypes (penile (on the body of penis), penoscrotal (at junction of scrotum and penis), perineal and glandular (most common and found on the head))
- is associated with inguinal hernias and cryptochidism
- NEVER DO CIRCUMCISION ON THESE PATIENTS
- is associated with various disorders of sex development as well as 5-alpha reductase deficiency (however it can also just be by itself)
Aromatase deficiency
Autosomal recessive mutation in CYP19A1 gene that encodes for aromatase
- this lowers conversion of testosterone to estrogen and results in decreased estrogen and increased testosterone
can be 46,XX or 46,XY (if XY will be normal sexual development)
- in 46XY = abnormal sperm production and cryptochidism usually
- in 46XX = virilization and primary amenorrhea . Also presents with ambiguous external genitalia but has normal internal genital organs for a female
Both sexes show
- tall stature
- early onset osteoporosis
- hyperglycemia (built in resistance to insulin)
- weight gain and fatty liver
Treatment = estrogen and progesterone replacement therapy if female
- also surgical correction of ambiguous external genitalia based on gender identity
- also make sure to give calcium or vitamin D supplementation prescription for life
What do the two different ducts (mesonephric and paramesonephric) differentiate into?
(Initially both males and females have both)
Male = at week 8, testosterone and anti-mullarian hormone are produced and degenerate the mullarian (paramesonephric duct)
- wolffian/ mesonephric duct grows
- mesonephric duct derivatives = SEED
- seminal vesicles, epididymis, ejaculatory duct, ductus deferens
- bulbourethral glands and spongy urethra = phallic urogential sinus
- prostate = pelvic part of the prostate
Female = at week 8 there is no testosterone and anti-mullarian hormone so the mullarian duct doesnt degenerate. Instead the wolffian duct does degenerate. Both mullarian ducts fuse near the sinus tubercle.
- unfused paramesonephric duct = uterine tubes
- fused paramesonephric ducts = body and cervix of the uterus. Also upper portion of vagina
- sinus tubercle = lower vagina
What structure in the body also shares embroylogic origin with the paramesonephric duct?
The kidneys
- both develop from the common mesodermal ridge (intermediate mesoderm)
Development of the vagina
Begins when the caudal tip of the fused paramesonephric ducts contact the urogential sinus and forms the sinus tubercle at week 9
- tubercle = hymen in females And seminal colliculus in males (wolffarian ducts fuse)
Vagina has dual origin
- upper part = derived from the paramesonephric duct
- lower portion = derived from the urogential sinus
Double uterus
Caused when the inferior part of the mesonephric ducts dont fuse together and both touch the urogenital sinus
Double vagina
Forms if the sinovaginal bulb falls to fuse
- forms two vaginas each with a blind end cervix
Bicorunate uterus
Casued when the msot inferior portion for he paramesonephric duct is fused but the region just above is not
Produces a single inferior uterus canal with a bifid uterus pouch
Septate uterus
Forms due to failure of resorption of the paramesonephric duct septum
- forms a septum in the middle of the uterus but has 1 uterus and 1 uterus opening still
Unicorn ate uterus
Forms due to failure of one paramesonephric duct to form
- either is obliterated or develops as a “rudimentary horn” which is essentially a giant cyst
The other does develop and produces a half uterus
Cervical atresia
Caused by atresia of the paramesonephric duct on both sides
- results in atresia of the inferior cervix and obliteration fo the lumen of the uterine canal
Vaginal atresia
Occurs if sinovaginal bulbs do not develop at all
- results in atresia of vagina which results in a small vaginal blind pouch
How are genital glands in the female produced
Urethral and paraurethral glands are formed from the pelvic part of the urogential sinus
- form outgrowths of the urethra
Greater vestibular glands = phallic part of the urogential sinus
Primordial tissues of the external genitalia in both sexes
Genital tubercle = forms the primordium (head/glans) of the penis or clit
Urethral (urogential) folds = forms the ventral aspect of penis and penile raphe and labia minora
Genital Labioscrotal swellings = forms the scrotum, labia majora and mons pubis
Division of the cloaca
Causes during 4th-7th weeks of development.
Cloaca is divided by urorectal septum into
- urogenital sinus anteriorly
- anal canal posteriorly
1st part = vesicle part
- upper and largest part
- forms all of the urinary bladder except the trigone
2nd part = pelvic part
- in males = prostatic and membranous urethra as well as prostate gland (from prostatic urethra)
- in females = all urethra
3rd part = Phallic part
- in males = spongy urethra
- in females = gives rise to vestibule of the vagina
