Sexual Determination/Differentiation and Reproduction

hormone effects during development is ___, whereas in adulthood, these effects are ___

permanent; transient

sex determination

the process by which the decision is made for a fetus to develop as a male or female

• CHROMOSOME driven

• if the sperm that enters the egg has a Y chromosome = male

• if the sperm that enters the egg has a X chromosome = female

• mother provides X chromosome

sex differentiation

the process by which individuals develop either male or female bodies and behaviors

• HORMONE driven

bipotential gonads

• when gonads are first made, they are bipotential = same gonad can become either testes or ovaries

• occurs at 6 weeks of gestation until 8 weeks

SRY gene

• sex-determining region of the Y chromosome

• codes for the development of testes

• ~8 week gestation

what occurs to gonads without SRY gene?

ovary forms

• sexual determination in the absence of gene

hormones secreted early on by gonad, mainly from testes, direct _____ of internal and external sex organs

sexual DIFFERENTIATION

wolffian ducts

• early sexual differentiation

• in males

• precursor to the male system

  • develops into the epididymis, vas deferens, and seminal vesicels

  • mullerian system shrinks

mullerian ducts

• early sexual differentiation

• in females

• precursor to female system

  • develops into the oviducts, uterus, and vagina

  • wolffian system degenerates

If testes are present, which hormones will be present for sexual differentiation?

• anti-mullerian hormone (AMH)

• testosterone

• dihydrotestosterone (DHT)

anti-mullerian hormone

• causes regression of the mullerian system in males

testosterone

• masculinizes the internal organs by promoting development of the wolffian system

dihydrotestosterone (DHT)

• converted from testosterone via 5alpha-reductase

• masculinizes external structures

estradiol in males

• testosterone can be aromatized to estradiol via aromatase

• masculinizes the brain

sexual differentiation of external genitalia

• external structures are also bipotential at 6 weeks gestation

• genital tubercle, urogenital sinus, and anal fold

• the presence of DHT masculinizes external structures

• the absence of DHT feminizes external structures

what is responsible for determining if the testes will be made?

SRY gene

what causes the mullerian system to regress in males?

anti-mullerian hormone

which hormone is responsible for masculinizing the external genitalia?

dihydrotestosterone

Turner’s Syndrome

• single X chromosome

• develops as a female due to lack of SRY gene, with abnormal ovaries

  • no steroid hormone production or eggs = infertile

  • underdeveloped cardiovascular system

• estrogen treatment induces breast growth and a female-typical puberty

Klinefelter’s Syndrome

• extra chromosome, XXY

• masculine body develops because of the Y chromosome

• however, low testosterone production = little to no sperm produced = infertile

• with low testosterone, there is also low DHT, which means external structures are also underdeveloped (micropenis)

• hormone replacement therapy is also required for secondary sex characteristics

congenital adrenal hyperplasia (CAH)

• normally, the HPA axis has CRH —> ACTH —> cortisol

• but these pts lack the enzyme (21-hydroxylase) that produces cortisol, so there is no negative feedback

  • results in a much higher amount of hormone production, and the adrenal gland becomes enlarged

• the precursor that makes cortisol (17-OHP) builds up, and the adrenal gland can turn the 17-OHP into other androgens like testosterone to relieve some of the build up of 17-OHP

  • external genitalia in females is partially masculinized because of increased exposure of DHT during development

• can occur in XX or XY

• exogenous cortisol given after birth to halt excess androgen production

androgen insensitivity syndrome (AIS)

• only in XY people with defective androgen receptors (androgens cannot have action)

  • testosterone and androgen have no effect

• will develop testes (Y chromosome)

• will produce testosterone/DHT, and AMH

• ONLY AMH will act because its not an androgen

  • will suppress mullerian system, but wolffian system will not be developed because no testosterone —> no differentiated internal organ system

  • infertile

• genotype = male with small testes (but no female/male internal machinery)

• phenotype = female (DHT unable to act on receptors will allow external female genitalia to develop)

sexual dimorphism

males and females exhibit marked sex differences in appearance

• sex differences in the brain refer to differences in the number or density of neurons, dendritic branching, or connectivity

sexual dimorphism in rat brain

• sexually dimorphic nucleus of the POA (SDN-POA) is larger in males than in females

  • important for reproductive behaviors in males

• due to the peak in testosterone perinatally (just before and around birth) NOT because of peak in testosterone again during puberty

hormone exposure during ____ ____ of utero development have brain developmental effects

critical window

organizational effect of estradiol

• PERMANATELY alters the brain

• alters apoptosis, changes synaptic connectivity, and affects densities

organization vs activation effect of hormones

• organizational

  • occurs early in development during the critical period (when brain is still developing)

  • structural changes in brain

  • e.g. estradiol masculinizing the brain

• activational

  • transient

  • biochemical changes

  • occurs during adulthood

  • no sensitive period

• the timing of the hormone’s action will determine if it will be organizational or activational

why aren’t female brains masculinized during fetal development?

1. ovaries are quiescent until puberty (does not produce gonadal hormones until puberty)

2. maternal estrogen in developing females does NOT enter the brain due to alpha-fetoprotein, which is produced by both male and female fetus

pathway for masculinization of the brain

• maternal estrogen circulating is bound by alpha-fetoprotein, but testosterone is an androgen, so it cannot be sequestered by this protein

1. testes releases T

2. T molecules enter neurons in the brain

3. many hypothalamic neurons produce aromatase, which will convert testosterone into estradiol

4. estradiol binds to the estrogen receptors, and the estrogen-receptor complex will alter gene expression after binding to DNA in the nucleus

purpose of gonads

1. production of gametes (sperm or egg)

2. production of steroid hormones

• hormones are required for the development of the body and the brain, production of gametes, and encouraging behaviors that bring gametes together

male gonads

• testes

• primarily produces testosterone

  • androgen

female gonads

• ovaries

• primarily produces estradiol and progesterone

  • estrogen and progestin

gonadal steroids ___ reproductive behavior

activate

• circulating gonadal steroid hormones act upon the neural circuitry already in place in the brain, and are required for males and females of many species to engage in sexual activity

estrous cycle

• in female rats, they ovulate (release eggs) every 4-5 days

• controlled by hormones via the hypothalamic-pituitary-gonadal (HPG) axis

female HPG axis

1. hypothalamus releases GnRH in a pulsatile fashion

2. GnRH stimulates anterior pituitary to release follicle stimulating hormone and luteinizing hormone

3. FSH acts on the ovary to cause development of the follicle; LH increases release of estradiol

• estradiol acts to increase further LH secretion (POSITIVE feedback), resulting in a surge of LH that causes ovulation

4. during ovulation, progesterone production then increases, inhibiting the hypothalamus from releasing more GnRH (negative feedback)

5. If the egg isn’t fertilized, progesterone drops and the cycle starts over

• if the egg is fertilized, the progesterone stays high to put a hold on the ovulation cycle

estrus phase

• the rise in estradiol followed by progesterone during the ovulatory cycle are integral for female sexual behavior

  • increases receptivity and motivation for sex during behavioral estrus

  • a female not in estrus will fight a male who makes advances

the hormones that lead to ovulation in a female are the ____ ____ that increase her receptivity and motivation

same ones

• maximal channels of reproductive success via fertilization

• energy efficient

• eggs are limited

• reduces risky behavior

hormones associated with maternal behavior and lactation ____ GnRH and reproductive cyecle behavior

inhibit

oral contraceptive contain _____ that inhibits release of ____-

synthetic progesterone; GnRH

• progesterone halts the reproductive cycle, and acts as negative feedback

• lack of GnRH prevents release of FSH and LH, so no egg is released by thr ovary

• sometimes estrogens are added to the pill for physiological benefit, but progesterone is the active ingredient

male HPG axis

1. hypothalamic cells release GnRH in a STEADY state, not in pulses like in female

2. this results in the testes producing testosterone in the LEYDIG cells and sperm in the SERTOLI cells

• because the male axis is less pulsatile, production of T and sperm remain fairly consistent once they begin at puberty (unlike female cycling)

neural circuitry in female rats

1. centrally (in brain and spinal cord), estrogen acts to increase dendritic ranching and connections of neurons in the ventromedial hypothalamus and periaqueductal gray

• the VMH sends axons to the periaqueductal gray in the midbrain, which projects to the medullary reticular formation in the hindbrain

• this is turn projects to the spinal cord via the reticulospinal tract

• as a male mounts, sensory information that comes in via the spinal cord combines with info from the brain, and female reflexes lordosis

1. in the periphery, estrogen increases sensitivity of sensory fields in the rump

2. estrogen also stimulates production of progesterone receptors, which is important for behavioral receptivity and motivation

3. 
   

neural circuitry in male rats

1. vomeronasal organ detects pheromones which activate male arousal

2. the vomeronasal organ info is sent to the accessory olfactory bulb, which projects to the medial amygdala, and in turn to the mPOA

3. medial preoptic area (mPOA) coordinates male copulatory behavior

• seems to integrate hormonal and sensory info

1. the mPOA sends axons to the ventral midbrain then to the basal ganglia to coordinate mounting

2. axons also project through brainstem nuclei to the spinal cord