Reproduction 1 Flashcards
describe the determinants of sexual differation
The type of sex: genetic, genotypic, or chromosomal
determines
gonadal sex: ovaries+/-female fetal tract or testis+/-male fetal tract
determines
genital or phenotypic sex with external sexual characteristics - most importantly external genitalia from lower fetal tract development
determines????
gender identification
What are the characteristics of genetic/genotypic/chromosomal sex and how is it identified?
determined by sex chromosome endowment: XX, XY (especially the Y determined at fertilization)
Karyotyping
What are the characteristics of gonadal sex and how is it identified?
determined by normal differentiation and especially the activation of SRY/TDF to yield male at about 7 weeks and female at 11 weeks
histology of gonads
What are the characteristics of genital/phenotypic sex and how is it identified?
determined by the activation and integration of
- neuroendocrine axes
- paracrine, endocrine control of genital tract development
physical exam
What are the characteristics of gender identity?
independent of genotype, unknown
discuss the general male genetic identity
Y chromosome required for testicular development with rare exceptions
Sry - sex determining gene on Y chromosome
XY with no Sry develop ovaries
XX with added Sry develop testis
X chromosome encodes androgen receptor
discuss the general female genetic identity
Ovary development depends on XX and no Y
Loss of one X results in ovarian dysgenesis but no loss of female ducts or genitalia
When do primordial germ cells migrate to the gonadal ridge?
5-6 weeks of gestation
is the gonadal ridge male or female specific?
neither - it is indifferent
What are the gene factors that determine maleness?
Sry is a transcription factor for Sox9, which induces proliferation of the primitive sex cords
What are the gene factors that determine femaleness?
Rspo1 and Wnt4 drive developmental progression, but ovary development will occur regardless due to lack of Sry
What do female internal genitalia develop from?
the cortex of the gonadal ridge
What do male internal genitalia develop from?
the medulla of the gonadal ridge
What are the three structures of the indifferent duct system?
mesenephros
mullerian duct
wolffian duct
What is the function of the mesenephros
produces urine during 6-10 weeks gestation and acts as a transient kidney for the developing fetus
What induces the regression of the mullerian duct in males?
AMH and inhibin B made by sertoli cellls
What stimulates the formation of internal genitalia in males?
Testosterone and DHT - androgens formed by Leydig cells
What induces the regression of the wolffian duct in females?
absence of testis, not the presence of ovaries!
What does the mullerian duct differentiate into in females?
top: fallopian tubes
middle: uterus
bottom: cervix and upper third of vagina
What does the genital tubercle develop into?
males: glans penis
females: clitoris
what doe the urogenital folds develop into?
males: ventral penis
females: labia minora
What does the urogenital sinus develop into?
males: prostate
females: lower vagina
What do the labioscrotal folds develop into?
males: scrotum
females: labia majora
What do the penis, scrotum, and prostate require?
The conversion of testosterone into DHT
What causes developmental defects in male external genitalia?
inhibition or mutation in converting enzyme 5-alpha-reductase
What are some general features of mitosis?
somatic cells only. daughter cells are genetically identical
What are some general features of meiosis I?
germ cells, duplication of DNA, recombination of chromes = genetic diversity. Chromosomes split in meiosis I
What are some general features of meiosis II?
no duplication, chromatids split, 4 daughter cells
What are the three main cell types in the testes?
gametes: sperm
sertoli cells: secrete AMH and inhibin B
Leydig cells: synthesize and secrete testosterone/DHT
What are the cell types of the ovaries?
Gametes (ova) and follicular cells are the follicles
What does follicular maturation result in?
Granulosa cells – secrete and synthesize estrogens and progesterone
Thecal cells – make androgens
What does DHT stimulate development of?
prostate and external genitalia
What does testosterone stimulate development of?
male internal genitalia
What does the wolffian duct differentiate into in males?
top: epididymus
middle: ductus deferens
bottom: seminal gland, ejaculatory duct
What is unique about Meiosis I in females?
arrested at diplotene of prophase until activation (puberty to 45+ years)
What causes meiosis arrest, and what produces it?
Oocyte maturation inhibitor (OMI), secreted by follicular cells in ovary
what is unique about meiosis II in females?
arrested at metaphase II until fertilized by sperm
discuss spermatogenesis in males
ongoing process from puberty through old age
discuss some structural errors that can result in chromosome abnormalities?
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 chromosomes attached to form a ring
what can happen if part of the Y chromosome containing the Sry gene gets translocated to the X?
XX female with male phenotype due to presence of Sry gene - this happens because X is inactivated
XY with female phenotype due to lack of Sry gene
What is the genotype of Turner’s Syndrome?
XO
What is the genotype of Klinefelter’s Syndrome?
XXY
What is Klinefelter’s Syndrome usually a result of?
meitotic non-disjunction
What is Turner’s Syndrome characterized by?
Gonadal dysgenesis - ovaries do not develop and become a streak of fibrous tissue
Although one X becomes inactivated later in life, and thus only one is necessary for life, at this stage you must have both Xs for ovary development
Discuss some physical presentations of a person with Turner Syndrome
Short statue, shield chest, webbed neck, upper torso deformities. Most do not go through puberty or have menstrual cycles
Discuss some physical and hormonal traits of someone with Klinefelter’s Syndrome
Patients have a Y chromosome - testes are present but are small and hyalinated, and they are infertile
Testosterone is low due to testicular dysfunction
Gynecomastia: elevated estradiol
micropenis, eunuchoid body: lower body > than upper body by at least 2” with short arms
What is the genetic etiology of hermaphroditism?
60% XX
20% XY
20% mosaicism/chimerism
What is the phenotype of hermaphroditism?
male/female designation is based on which gonad is present (internal or external for males)
What is male pseudohermaphroditism?
Testes present, but some or all female internal/external genitalia also present
What is an example of male pseudohermaphroditism?
Androgen resistance due to loss (complete) or mutation (partial) in X-linked androgen receptor gene (karyotype 46, XY)
discuss the hormonal and phenotypic traits of male pseudohermaphroditism due to complete androgen resistance
Y chromosome induces mullerian duct regression and testes (undescended)
lack of androgen effects (no Wolffian duct development, no external genitalia)
hormones: androgen levels are high due to lack of feedback, high estrogens lead to development of female body characteristics
phenotype: female with blind vaginal pouch
discuss the hormonal and phenotypic traits of male pseudohermaphroditism due to partial androgen resistance
Y chromosome induces mullerian duct regression and testes (undescended)
Wolffian duct develops, gynecomastia
hormones: Androgen levels are high due to lack of feedback, estrogen levels high (for male)
phenotype: ambiguous with blind vaginal pouch (under masculinized)
What is female pseudohermaphroditism?
Ovaries present, but some or all male internal/external
genitalia also present
female pseudohermaphroditism is a result of what?
Developmental defect – not due to chromosomal abnormality
What is the phenotype of female pseudohermaphroditism?
Virilization due to increased androgens. Ambiguous genitalia, advanced skeletal age
What are some examples of female pseudohermaphroditism?
Fetal congenital adrenal hyperplasia ** most common
Maternal androgen excess due to adrenal or ovarian tumors, possibly also due to progestational drugs (birth control)
what is “true” hermaphroditism?
Both testes and ovaries present “gonadal” sex, but phenotypic sex ambiguous (XX hermaphrodites typically raised as females)
Cryptorchidism (undescended testes) and hypospadias are common
No spermatogenesis because other Y genes not present
what might be a cause of true hermaphroditism?
Possible SRY translocation or loss of RSPO1 gene (testes repressor)
