[IEMR59-60.6]Sexual Differentiation and Fetal Endocrinology Flashcards
During what time in a female fetuses’ life does she have the greatest number of gametes? What is that approximate number?
During gestation or a couple of months before birth. The number is about 7 million.
Why does the corpus leteum die off during 8-9-12 week of gestation?
The secretion of hCG drops off once the placenta is large enough to be able to synthesize progesterone while utilizing the mother’s cholesterol found in circulation
What happens to the levels of DHEA, cortisone, DHEAs, cortisol and ACTH between 10 weeks gestation, birth and after birth?
All of the levels slowly rise to a peak value at birth. They hyperbolically drop to reach a horizontal asymptote during the first 6 weeks postnatally
What are the types of sex you see in the reproductive system?(2points)
Fertilization is the chromosomal type sex occurring between gametes. Bipotential sex is the type of sex that occurs between gonads.
How is cholesterol produced in the fetus?
It is produced in the gonads and the adrenal cortex
How does the placenta produce cholesterol?
It can’t. The placenta depends on the mothers circulating LDL, VLDL, HDL or chylomicrons.
The production of what hormone is very important for lung development before birth?
cortisol
What are the internal duct systems found in male and female?
The Mullerian system and the Wolfrian system.
How is cortisol production regulated in the fetus?
It is converted to cortisone in the fetus
The hypothalamo-hypophyseal system is in what type of secretory state during the 13-16 week of gestation?
Hypersecretory
After birth what happens to the concentration of estrogen?
It drops immediately
Initially, what is the purpose of the hCG hormone in pregnancy?
the small placenta secretes hCG to stimulate the corpus luteum to produce estrogen and progesterone
What are important enzymes in the synthesis of glucocorticoids and what steps do they catalyze?(2 -4 points)
21-hydroxylase synthesizes the conversion of 17-OH-pregnolone to 11-deoxy cortisol. 11β-hydroxylase catalyzes the conversion of 11-deoxycortisol to cortisol
What are the meiotic pauses in spermatogenesis?
none, they go straight through. There are no pauses.
Most of the thyroid hormone produce in the fetus is what?
Mostly T4
A small amount of what type of thyroid hormone is produced in the last 2 weeks of gestation?
Triiodothyronine
The Hypothalamo-Hypophyseal system is in what type of secretory state during the 5-13 weeks period of gestation?
hyposecretory
How is the production of growth hormone receptor regulated?
There is delayed expression or neutralization of the growth hormone receptor
What enzyme is needed for pregeneolone or progesterone to be shuttled over to glucocorticoid synthesis or androgen synthesis?
17-α-hydroxylase
What steroid abnormality do you see with 11-β-hydroxylase deficiency?(4 points) What are the symptoms?(2 points)
decreased cortisol, decreased aldosterone, increased androgens and increased DOC. You’re going to see mild masculinization and hypertension.
How is the delivery of substrates to the fetus controlled?
They’re controlled by the maternal-placental interface
What is the concentration of estrogen around 20 weeks gestation to birth?
It starts off at like 800 and it rises to about 1300 units and then drops significantly at birth
How does GH levels change during prenatal development for the fetus? How does this affect IGF levels?(before birth and after birth)
There is a small increase that peaks at about 25 weeks. It starts to drop after this point continuing to drop pass birth. IGF linearly rises to a peak around birth where is hyperbolically drops to a stable level throughout the first few weeks of development
What type of cellular division takes place with XY germs cell during the migration to the genital ridge? What type of division takes place after this?
They go through a mitotic division during their migration. No division takes place after this. They become arrested in G0 until after birth.
How does prolactin levels change in the fetus from before birth to after birth?
The prolactin levels start to rise at 30 weeks gestation, peaks at birth and then starts to drop after birth during development
What are the different substrates involved in the synthesis of glucocorticoid? You should start off with cholesterol.( 6 points)
Cholesterol is converted to pregenolone which is converted to 17-OH-pregnolone, which is converted into 17-OH progesterone, which is converted to 11-deoxycortisol which is converted to cortisol.
In the fetus what is the relative concentration of LH and FSH
They’re relatively low
What enzyme is used to carry cholesterol into the mitochondria for steroid biosynthesis in the adrenals to take place?
Steroid Acute Regulatory Protein
What type of cellular division takes place with XX germ cells during the migration to the genital ridge? Where do they enter after this point? What type of division takes place after this point? The surviving germ cells become surrounded by what?
Mitosis takes place during the migration to the genital ridge than to the ovaries. They start to undergo meiosis becoming arrested at prophase I by birth. The surviving germ cell becomes surrounded by granulosa cells.
When is there a peak of secretion for the hypothalamo-hypophyseal system?
20 weeks gestation
The promordial germ cells must migrate to what structure in the developing gonads to survive?
The genital ridge
How is temperature regulated in the fetus?
the maternal-placental interface
To a large extent, how is hormonal regulation in the fetus completed?
minimal
When does negative feedback develop in the hypothalmao-hypophyseal system?
After 20 weeks gestation when secretion peaks
Primordial germ cells migrate to developing gonads at what time?
Week 5
What type of substrate is used by the young fetal adrenal to synthesize progesterone?
the fetus can’t synthesize progesterone
How is the production of insulin and glucagon regulated?
There is limited hormone secretion
How are mineralocorticoids and glucocorticoids produced in the fetus? What substrate is used?
They’re produced in the adrenal cortex from maternal-placental progesterone
What are the substrates used to synthesize aldosterone?(4-6 points)
Cholesterol, pregenolone, progesterone, DOC, corticosterone and aldosterone
If there is a lack of 17-α-hydroxylase, there will be a build-up in what type of metabolites?
There will be a build-up in mineralocorticoidsq
What hormones in the fetus are going to be really important close to birth and after birth?(3 points)
Cortisol, thyroxine(T4) and triiodothryonine (T3)
What happens during week 5 of development when you considering the migration of primordial germ cells?
they migrate to developing gonads
What hormone is essential for CNS development?
Thyroid hormone
How is thyroxine production regulated in the fetus?(2-4 points)
Thyroxine is converted into rT3, T4s, rT, 3S
After birth what happens to the levels of testosterone?
Testosterone spikes up during the first few weeks after birth
When does meiosis begin in the testes?
puberty
What are the number of cells, chromosomes and the types of cells in the relevant stages of mitosis/meiosis in spermatogenesis?(5 points)
4 diploidy spermatogonia(spermatogonium singular) are at the beginning of the process. The spermatogonia mitotically divide to four diploidy primary spermatocyte. The four primary spermatocytes continue to meiotically divide to form four haploidy spermatocytes. The four haploidy secondary spermatocytes complete meiosis and form 4 haploidy spermatids. The spermatids go through spermiogenesis and form 4 spermatozoa.
What are the number of cells and chromosomes for the relevant stages of mitosis/meiosis in oogenesis?(6 points)
Oogonium is in the beginning and they’re diploidy with 2 cells in the beginning. They mitotically divide and form 4 diploidy primary oocyte. This all happens before birth. Meiosis begins but the primary oocyte is arrested at prophase I. After puberty, the beginning of the second meiotic division for the primary oocyte takes place which forms haploidy oocytes and 1 polar body. The cell continue to meitotically divide until it is arrested at metaphase II as two haploidy secondary occyte and polar body I
If there is a 21 hydroxylase deficiency what do you see? (3 points) How this affect males? How does this affect females? What are the symptoms?
You get a decrease in glucocorticoids, a decrease in glucocorticoids but an increase in androgens. This doesn’t affect males but this does lead to masculinization of females. You will have salt loss for both male and female.
What stages are the meiotic pauses in Oogenesis?
Prophase I until puberty and Metaphase II from just before ovulation to fertilization
What type of staining is used to recognize primordial germ cells in the yolk sac during development at week 3 of development?
alkaline phosphatase staining
What steroid abnormality do you see with 3βhydroxysteroid dehydrogenase deficiency? (3 points) What are the symptoms?
you have decreased aldosteorne, decrease cortisol and increased DHEA. There is mild masculinization and salt loss.
During birth, what is the relative amount and time of TSH hormone that is produced?
There is a massive amount produced which peaks within the first 60 minutes of delivery which drops off after the next few days
What type of substrate is used by the young fetal adrenal cortex to synthesize DHEA?
The maternal-placental progesterone
How is triiodothyronine production regulated in the fetus?(2 points)
It is converted into T3S, T2
What type of secretion of LH and FSH occur in men? What type of secretion occur in women?
It is a static type of diurnal secretion. Women have a more cyclic pattern.
How does the placenta synthesize esotradiol?
It does this by coordinating with the adrenal cortex. The adrenal cortex receives progesterone and allows it to go down the 17-hydroxylase pathway to synthesize DHEA to make androgens. The androgens are aromatized in the placenta to synthesize estradiol.
What are enzymes of clinical importance in the synthesis of aldosterone in the adrenals? What steps do they catalyze?(2- 4points)
21 hydroxylase catalyzes the conversion of progesterone to DOC. 11β-hydroxylase catalyzes the conversion of DOC to corticosterone
What is the concentration of hCG in the fetus from 10 weeks gestation to 30 weeks gestation
There is a drop from 2000 units to 30 units
Fetal thyroid depends on what?
fetal TSH
The primordial germ cells generated in yolk sac during what time in development?
Week 3
What type of steroid abnormality do you see with 17-α-hydroxylase deficiency?(5 points) What are the symptoms? (4 points
Decreased cortisol, decreased androgens, increased DOC, increased aldosterone and increased corticosterone. Hypertension, hypokalemia, alkalosis and sexual infantilism
How is the production of the thyroid hormone receptor regulated?
There is delayed expression or neutralization of the thyroid hormone receptor
How is the production of growth hormone, thyroid hormone, thyroid hormones, catecholamines, estrogens and glucagon regulated?
They’re is delayed expression or neutralization of the receptors
What are the different mechanisms utilized to neutralize hormone actions in the fetus?(3 points)
productive of inactive metabolites, delayed expression or neutralization of receptors; limited hormone secretion
How is the production of triiodothyronine, thyroxine and cortisol generally regulated?
They’re converted into inactive metabolites
Do you see significant differentiation between male and female genitalia at 6-7 weeks?
No
Do you see any significant differentiation of the external genitalia of the during 8-9 weeks of development?
No
Do you see any significant differences in the differentiation of the genitalia of developing males and females at 15 weeks for females or 11 weeks for males?
Yes, this is when you start seeing a significant difference
The urogenital sinus becomes what structure in the developing male? What does it become in the developing female?
It becomes part of the prostate in the developing male and it forms part of the vagina i the developing female
How many months does it take to decipher between a developing male and a developing female?
It takes two months
What happens if a developing male doesn’t have sufficient secretion of the anti-Müllerian duct hormone?
The person will have vestigial ducts which are usually asymptomatic. Sometimes they become entangled in other structures but this is rare.
What stimulates the development of the Wolfian Ducts? What happens to these ducts in developing females? Why do the Müllerian Ducts persist to grow?
testosterone; These ducts deteriorate due to the lack of testosterone; The Müllerian ducts grow due to the lack of the anti-Müllerian hormone
What happens if there is a lack of testosterone secretion in a developing neonatal male? What is the phenotypic description?
The lack of testosterone would result in the failure of proper differentiation of the external gentalia. The individual would “look” female but definitely be male.
What chromsomal factor presence stimualtes the differentiation of the male gonads to become testes?
SRY factor in chromsome Y
What cell produces anti-Müllerian hormone? What cell produces testosterone?
sertoli cells; Leydig cells
What stimulates the development of the penis and the scrotum?
dihyrotestosterone
What is the substarte and enzyme catalyzing the formation of dihydrotestosterone?
The substrate is testosterone and the enzyme catalyzing the conversion is 5-α-reductase
What stimulates the Wolffian ducts to form the epididymis, ductus deferens and seminal vesicles?
testosterone
Testosterone stimulates the Wolffian ducts to develop into what structures?(3 points)
epididymis, ductus deferens and seminal vesicles
What stimulates the formation of the ovaries from the primordial undifferentiated gonads?
Nothing, it is due to the lack of SRY from the Y chromosome.
In the absnece of MIH, the Müllerian ducts forms what structures?(2 points)
uterus and uterine tube
In the absence of testosterone, the Wolffian ducts fors into what structures?(3-5 points)
None*5; however, thre is the default development of vagina and female external genitalia due to the lack of testosterone
The presence of what hormones stimulate female sex differentiation?
the presence of estrogen and estradiol
Gonadal dysgenesis is the result of what?
The lack of the SRY gene from the Y chromsome
The lack of the WT-1 gene results in what reproductive abnormality?
male psuedohermaphrodite
A defect in the SOX9 gene results in what reproductive abnormality?
XY male psuedohermaphrodite
What happens if you get excess DAX1?
You get a mixed gonadal dysgenesis
The loss of what genetic factors would result in complete gonadal agenesis?
The lack of SOX9 and the lack of SRY
Does sexual differentiation occur earlier in females or males?
It occurs earlier in males
What is the problem with congenital adrenal hyperplasia male patients?
They don’t have production of cortisol. Androgens are produced but they can’t inhibited the production of ACTH from the anterior pituitary gland. Therefore, the adrenal glands get larger and larger.
What is the reproductive problem with patients who have testicular feminized males?
There is an issue with the testosterone receptors. They’re males but phenotypically femlaes due to the lack of testosterone action at multiple locations in the male reproductive system.
How does a lakc of 5α-reductase affect male reproductive development?
The patients don’t have a penis or a scrotum
A genotypic male (XY) is born with feminized external genitalia. The testes are retained within the abdominal cavity, and the internal reproductive tracts exhibit the normal male phenotype. Which of the following could account for this abnormal development?
5α-reductase deficiency
In a genotypic male, the testes fail to develop, and do not secrete testosterone or Müllerian regression factor. What would best describe the in utero reproductive system development of this individual ?
Female type internal reproductive tract and female-type external genitalia
An XX genotypic infant is born with ambiguous genitalia. Laboratoryexamination reveals hypoglycemia, hyperkalemia, and salt wasting. Serum 17-OH progesterone is markedly increased. What the most likely diagnosis?
21-hydroxylase deficiency
What reproductive problems could result in an ovary only 46XX psuedohermaphrodite?
21-hydoxylase deficiency; 11-β-hydroxylase deficiency; 3β-hydroxysteroid dehydrogenase deficiency or maternal administration of exogenous androgens
– 20-alpha-hydroxylase deficiency
– 3-beta-ol-dehydrogenase deficiency
– 17-alpha-hydroxylase deficiency
– 17,20-desmolase deficiency
– 17-ketosteroid reductase deficiency
46XY testes only male psuedohermaphrodite with inadaqute virlization of the male external genitalia
What percentage of hermaphrodite cases are true hermaphrodites?
less than 10% of intersex cases
Testis plus streak has what type of gonadal disorder? What is the prevalence? What is the chromosomal abnormality?(2 points) There is a high risk for what disorder? What about the reproductive and anatomical status(2 points)
Mixed gonadal dysgenesis; Second most prevalent; 45XO, 46XY mosaicism; There is a high risk for neoplastic degeneration after puberty; theyre may be two bilateral Müllerian ducts and interfile dysgenic testes
Streak plus streak has what type of gondal disorder? What are the chromosomal abnormalities?(3 points) What chromosomal abnormalities is prone to malignancy? What type of phenyotypic presentation for all of these patients?
bilateral gonadal streaks; 45XO(Turner’s), 46XX and 46XY; female
Klinefelter’s Syndrome: Karyotype?(2 points) Mullerian Duct Derivatives? Wolffian Duct Derivatives? Genitalia? inheritance?(3-4 points) Gonadal description?(2 points) How does this effect reproduction? How does the body try to compensate? What is the hormone profile?
47XXY, 46XY/47XXY; Absent Mullerian duct derivatives; normla Wolffian duct derivatives; male genitalia; sporadic inheritance, nondisjunction during mitosis, nondisjunction during second division of meiosis; small firm testes and semineferous tubules dysgenesis; azoospermia, no reproduction; Leydig cell hyperplasia; decreased testosterone but increase in LH and FSH postpubertally
Turner’s Syndrome: Karyotype?(2 points) Inheritance? Genitalia? Wolfian duct derivatives? Müllerian duct derivatives? Gonads?(1-2 points)
45XO or 45XO/46XX; it is associated with other preliminary diseases; female genitalia; Müllierian ducts is hypoplastic female; immature ovaries or gonadal streak
Poor to normal virilization at puberty: gynecomastia; disproportionately long legs; decreased facial/axillary hair; learning difficulties; obesity
Klenfelter’s Syndrome
lymphedema, web neck, cardiac defects, urinary tract malformations, horseshoe kidneys
Turner’s syndrome
short stature, short neck, hypoplastic nails, micrognathia, scoliolis, autoimmune thyroid disease, learning difficulties
Child with Turner’s Syndrome
pubertal failure, primary amenorrhea, HTN, obesity, dyslipidemias, impaired GLC tolerance, insulin resistance, CVD
Adult with Turner’s syndrome
A 46,XX newborn is noted to be highly virilized and salt losing. The diagnosis is congenital adrenal hyperplasia. The most likley enzymatic defect is in
21-hydroxylase
A 20-year-old female complains of amenorrhea, noting she has never had a period. On physical examination the patient is noted as having well developed breasts, but a small and shallow vagina. One round mass is present in the right inguinal region; a similar mass is present in an inguinal hernia on the left. The patient’s buccal smear is negative for Barr bodies. What is the problem?
Androgen Insensitivity syndrome
