Reproduction 1 Flashcards
Describe the hierarchy of determinants of sexual differentiation.
Slide 6
Chromosome
gonads
genitalia
gender identity
Genetic are chromosome and gonads
Hormones, internal structures, external structures, social behavior - genitalia and gender identity
Define sex vs gender.
Sex – biologically determined
chromosomal complement
“sex differences” – refer to biologically inherent differences
Gender – socially determined
usually related to appearance: genitalia and secondary sex characteristics
Describe sexual determination.
Female vs male? How is gonadal sex determined?
Describe the sex determining gene/transcription factor. Major target?
Genotype (chromosomal sex):
46, XX = female sex
46, XY – male sex
Gonadal sex (determined by chromosome):
Y chromosome determines male gonads (testes)
SRY gene = sex determining region Y
(also called TDF – testis determining factor)
SRY is a transcription factor – major target is SOX9
How do you characterize and identify genetic, genotypic or chromosomal sex?
Determined by sex chromosomal
endowment: XX, XY – especially the
Y determined at
fertilization
Karyotype
analysis
How do you characterize and identify gonadal sex
ovary/female fetal tract
testis/male fetal tract?
Determined by normal differentiation
and especially activation of SRY/TDF to yield male at about 7 weeks (female
about 11 weeks)
Histology of
gonad
How do you characterize and identify genital or phenotypic or body sex with external sexual characteristics – most importantly external
genitalia from lower
fetal tract development?
Determined by activation and
integration of
1) neuroendocrine axes
2) paracrine, endocrine control of genital tract development
Physical exam
How do you characterize and identify gender identification or
“behavioral sex”?
Seems independent of genotype, phenotype and hormones – may
involve rearing cues or psycho social factors or is unknown
Observation
And psychological
tests
Describe genetic sex for male. What is required for testicular development?
What happens to XY mice with no functional Sry?
XX mice with added Sry?
X chromosome encodes?
Y Chromosome: [Y defines the guy]. Required for testicular development (rare exceptions). Sry
= sex determining gene located on the Y chromosome
XY mice with no functional Sry develop ovaries
XX mice with added Sry develop testis
X Chromosome: X Chromosome – encodes the androgen receptor
What does ovary development depend on?
Ovary development depends on the presence of 2X and no Y chromosome
What does loss of one X chromosome result in?
Loss of one X chromosome results in ovarian dysgenesis but not loss of female ducts or genitalia
Explain dichotomous development of gonad, internal ducts, and external genitalia.
…
Describe primordial germ cells. When do they migrate to gonadal ridge?
Primordial germ cells (PGC) – migrate to gonadal ridge (5-6 weeks gestation)
Primordial (indifferent) gonad bipotential for testis or ovary
Primordial gonad is indifferent – not male or female specific. Bipotential development into either
testes or ovaries depending on specific gene factors.
What direct the specific development of gonad?
What gene expression patterns lead to gonad differentiation in male/female?
Germ cells direct the specific development of the gonad
Specific gene expression patterns lead to gonad differentiation
Male: Sry + Sox9
Female: Rspo1 + Wnt4
Male = SRY is gene that determines testis formation. Transcription factor for Sox9. Sox9 = induces proliferation of the primitive sex cords.
Female = Rspo1 and Wnt4 drive developmental progression, but ovary will develop regardless of
these factors due to absence of SRY gene.
Where do male and female internal genitalia develop from?
CORTEX – develops into female internal genitalia
MEDULLA – develops into male internal genitalia
Female internal genitalia develop from cortex of
gonadal ridge.
Male internal genitalia develop from medulla of
gonadal ridge.
Describe the embyronic development of the male gonad.
indifferent gonad= primitive sex cords
proliferation of sex cords (SRY, SOX9)
Penetration of medulla by sex cords
Differentiation of medullary cords- becomes testes
Describe embryonic development of female gonad.
indifferent gonad= primitive sex cords
sex cords disorganize-cortical epithelial cells proliferate
(due to absence of SRY)
cortical cords develop from cortical epithelium
Cells form clusters around germ cells - epithelial cells become follicular cells -ovary develops
Describe 3 main cell types in testes.
TESTES: 3 main cell types
Gametes (sperm)
Sertoli cells – secrete antimullerian hormone (AMH)
Leydig cells – synthesize and secrete testosterone/DHT
Describe the composition of ovaries.
OVARIES:
Gametes (ova)
Follicular cells
gametes and follicular cells = follicle
What does follicular maturation result in the formation of?
Granulosa cells – secrete and synthesize estrogens and progesterone
Thecal cells – make androgens
Depending on its chromosomal complement, an undifferentiated cell can be destined to proceed
in the male or female developmental pattern.
Describe the indifferent duct system.
Mesoneprhos – produces urine during 6-10
weeks gestation and acts as a transient kidney for
the developing fetus. (degenerates in both sexes)
Mullerian Duct – undergoes further development
in females. Also called “paramesonephric duct”
Wolffian Duct – undergoes further development
in males. Also called “mesonephric duct”
Describe the male internal genitalia.
Describe testes. What do sertoli cells make? What are effects?
What do Leydig cells make?
What effect does Wolffian duct have?
What is DHT?
TESTES –
Sertoli cells make AMH and Inhibin B – AMH induces regression of the Mullerian duct
Leydig cells make androgens: testosterone and DHT stimulate formation of internal genitalia from Wolffian duct: Testosterone: top = epidiymis, middle = ductus deferens, base = seminal vesicle, ejaculatory duct
DHT: prostate, external genitalia
Describe the female internal genitalia.
What induces the regression of Wolffian ducts?
Absence of Testes (not presence of ovary) induces regression of Wolffian ducts
Describe female internal genitalia:
How do mullerian ducts differentiate (top, middle, bottom)
Mullerian Ducts differentiate:
Top – fallopian tubes
Middle – fuses to become uterus
Bottom – cervix and upper 1/3 of vagina
Describe contrasting patterns of male and female differentiation of the internal genital ducts. Experiments of Alfred Jost (1953) → important determinants of these patterns.
Slide 21
What do penis, scrotum, prostate require?
What is effect of “propecia”?
-DHT
Penis, scrotum, and prostate require conversion of testosterone into DHT.
”Propecia” inhibits 5alpha-reductase
Inhibition or mutation of converting enzyme (5alpha-reductase) will cause developmental
defects in external male genitalia.
Describe the following as pertains to male:
genital tubercle
urogenital folds
urogenital sinus
labioscrotal folds
genital tubercle- glans penis
urogenital folds- ventral penis
urogenital sinus- prostate
labioscrotal folds- scrotum
Describe the following as pertains to female:
genital tubercle
urogenital folds
urogenital sinus
labioscrotal folds
genital tubercle- clitorus
urogenital folds- labia minora
urogenital sinus- lower vagina
labioscrotal folds- labia majora
Contrast mitosis and meiosis as it relates to the process of gametogenesis.
Define mitosis, meiosis I, and meiosis II.
Mitosis – somatic cells only. Daughter cells are genetically identical
Meiosis I – germ cells
Duplication of DNA. Recombination of chromosomes = genetic diversity.
Chromosomes split in meiosis I
Meiosis II
No duplication
Chromatids split
4 daughter cells
Define the following:
Gametogeneis
Spermatogenesis
Oogenesis
GAMETOGENESIS: process of forming a haploid gamete (spermatozoa or ovum)
SPERMATOGENESIS: specific to male
OOGENESIS: specific to female
Spermatogenesis =
4 daughter cells/germ cell
See diagram slide 26
When do chromosomes split?
Meiosis I
When do chromatids split?
Meiosis II
When is genetic diversity established in meiosis?
through recombination of chromosomes in meiosis I
Describe oogenesis.
When is meiosis I arrested?
Where is OMI secreted from and what effect does it have?
When is meiosis II arrested?
oogenesis =
1 daughter cell/germ cell plus polar bodies
Meiosis I is arrested at diplotene of prophase until activation (puberty to 45+ years).
Oocyte maturation inhibitor (OMI) is secreted from follicular cells in ovary and causes meiosis arrest.
Meiosis II is arrested at metaphase II until fertilized by sperm
Describe male spermatogenesis duration.
Ongoing process from puberty through old age
What composes a primordial follicle?
Primordial follicle = primary oocyte + follicular cells
Are there oogonia present at birth? Explain.
No oogonia are present at birth – all converted to primary oocytes or subject to atresia
List examples of chromosomal abnormalities.
Structural Errors =
Translocations – equal or unequal exchange of chromosomal material
Inversions – piece of chromosome gets inserted upside down
Deletions, Duplications – loss or addition of part of a chromosome
Rings - two ends of chromosome join to form a ring
Chimerism = genetically distinct cells (arising from different zygotes)
Mosaicism = cell specific chromosome differences (i.e. X inactivation) “calico cats”
Aneuploidy = abnormal numbers of chromosomes
“down syndrome = trisomy 21”
Describe a structural chromosomal abnormality.
Structural –
Part of the Y chromosome gets translocated to the X
XX female with male phenotype due to presence of SRY gene
XY phenotype with female phenotype due to lack of SRY gene – this happens because the X chromosome is inactivated
Explain the following chromosomal abnormalities:
XO
XXY
XY (2 possibilities)
XO – Turner’s Syndrome
XXY – Klinefelter’s syndrome (1:500 to 1:1000, most common chromosomal disorder in boys) – usually due to meiotic nondisjunction
XY – loss of X-linked androgen receptor (recessive) - pseudohermaphroditism
XY – loss of 5alpha-reductase gene
Describe Turner’s syndrome.
What karyotype?
Describe gonads.
Describe the phenotype.
45, XO KARYOTYPE “gonadal dysgenesis”
Both X chromosomes are required during development for oogonia. Ovary becomes a “streak” = fibrous tissue
Systemic phenotypic issues due to aneuploidy
Turner syndrome is characterized by gonadal dysgenesis – ovaries do not develop and becomes a
“streak” of fibrous tissue. Both XX chromosomes are required during early differentiation of the
ovary, although one X chromosome becomes deactivated later in life, so 2 copies are no longer
required. Chromosomal aneuploidy often results in multiple other systemic phenotypes, of which
the pathology is not completely understood. Turner syndrome patients have very short stature,
“shield” chest, webbed neck, and upper torso deformities. Most do not go through puberty or
have menstrual cycles.
Describe Klinefelter Syndrome 47.
XXY
Y chromosome: testes present (small, hyalinated); infertile
Testosterone is low (due to testicular dysfunction), micropenis
Eunuchoid body: lower segment greater than upper segment by more than 2”; short arms
Gynecomastia – elevated estradiol
Systemic phenotypic issues due to aneuploidy
Describe the etiology of hermaphroditism.
Etiology – Chromosomal (genetic); Hormonal (development) Hermaphrodite karyotype diversity: 60% are XX 20% are XY 20% mosaicism/chimerism.
Describe the following hermaphroditism phenotypes.
Male Pseudohermaphroditism
Female Pseudohermaphroditism
“True” hermaphroditism
Male Pseudohermaphroditism – Testes present, but some or all female internal/external genitalia also present
Female Pseudohermaphroditism – Ovaries present, but some or all male internal/external genitalia also present
“True” hermaphroditism – Both testes and ovaries present “gonadal” sex. Phenotypic sex ambiguous.
Describe Male Pseudohermaphroditism.
Complete:
What is present?
Describe phenotype for complete androgen resistance (hormones and phenotype)
Male Pseudohermaphroditism – Testes present, but some or all female internal/external genitalia
also present
Complete: loss of X-linked AR gene
Example: Androgen resistance due to loss (“complete) or mutation “partial” in X-linked
androgen receptor gene (karyotype 46, XY).
Phenotype for complete androgen resistance:
Hormones: Androgen levels are high (lack of feedback, estrogen levels high (for male). Gonadotropins?
Phenotype: female with blind vaginal pouch
Y chromosome – induces mullerian duct regression, testes (undescended); lack of androgen effects (no Wolffian duct development, no external genitalia)
High estrogens induce development of female body characteristics
Describe Female Pseudohermaphroditism. What is present? What causes it?
Describe the most common type.
Describe cause and phenotype.
Ovaries present, but some or all male internal/external
genitalia also present.
Developmental defect – not due to chromosomal abnormality.
1) Fetal congenital adrenal hyperplasia ** most common
2) Maternal androgen excess due to adrenal or ovarian tumors, possibly also due to
progestational drugs (drugs with progesterone-like action).
Phenotype: virilization due to increased androgens. Ambiguous genitalia, advanced skeletal age
Describe “true” hermaphroditism.
What is present?
Phenotypic sex?
Spermatogenesis?
External genitalia?
Both testes and ovaries present “gonadal” sex.
Phenotypic sex
ambiguous. XX hermaphrodites generally raised as females. Possible SRY translocation or loss of RSPO1 gene (testes repressor).
No spermatogenesis because other Y genes not present.
Differentiation of external genitalia is highly variable – ambiguous
Cryptorchidism (undescended testes) and hypospadias are common.
Describe Male Pseudohermaphroditism.
Phenotype for partial androgen resistance. What type of mutation? (hormones and phenotype)
What does Y chromosome do? High estrogens?
Phenotype for partial androgen resistance:
Partial: AR mutation – partially functional
Hormones: Androgen levels are high (lack of feedback, estrogen levels high (for
male). Gonadotropins?
Phenotype: ambiguous with blind vaginal pouch (under masculinized)
Y chromosome – induces mullerian duct regression, testes (undescended);
Wolffian duct develops, gynecomastia
Describe virilization by androgens?
What results?
Virilization by androgens- advanced skeletal “age”, clitoromegaly and other ambiguities of genital anatomy.
