reproductive system

what is gonadal function controlled by?

neuronal systems, the hypothalamus, and anterior pituitary

what neurons synthesize and secrete Gonadotropin-releasing hormone?

hypothalamic neurons

what does the neuron KNDy do?

integrates neuroendocrine, metabolic, and environmental signals

what is kisspeptin?

a neuropeptide that stimulates GnRH release

what produces kisspeptin?

KNDy neurons

define sexual dimorphism

two sexes of the same species having different morphological characteristics

define genotypic sex

refers to individual’s two sex chromosomes

define phenotypic sex

refers to the structures of the internal and external genitalia, expression of secondary sex characteristics, and behavior

from where do male and female gonads develop from?

the urogenital (gonadal) ridge

what do both male and female embryos initially have?

double set of embryonic genital ducts: the Wolffian and Mullerian ducts

differentiate into: Wolffian - male

Mullerian - female

from what do external genitalia develop from?

three primordial embryonic structures: urogenital fold, labioscrotal fold, and genital tubercle

what does the genital tubercle give rise to in males and females?

males: glans penis

females: the clitoris

when does sexual differentiation begin?

~6 weeks post fertilization

what happens during sexual differentiation in a male?

Sex Determining Region on the Y chromosome (SRY) gene expresses the product SRY protein

what is the critical window for the SRY protein?

must be present after 9 weeks or else testes will not develop and ovaries develop instead

what is congenital adrenal hyperplasia?

a loss-of-function mutation in the gene that expresses the 21 alpha-hydroxylase enzyme results in over-production of adrenal androgens

females with the disorder develop ambiguous genitalia

what is 5-alpha reductase deficiency?

this enzyme is necessary to convert testosterone to dihydrotestosterone (DHT). a loss-of-function mutation of the gene that expresses this enzyme results in low DHT levels, resulting into failure of fetal/embryonic development of male external genitalia. Males affected with this deficiency develop ambiguous genitalia.

give an overview of male sex differentiation

• the presence of SRY gene (on the Y chromosome)

• primordial gonads differentiate into fetal testes and result in sertoli cells and leydig cells

• sertoli cells produce:

  • anti-mullerian-hormone (AMH)

    • AMH produces a regression in mullerian ducts

• leydig cells produce:

  • testosterone

    • testosterone produces:

      • dihydrotestosterone

        • dihydrotestosterone allows the development of the: penis, scrotum, prostate

      • testosterone allows for the transformation of the wolffian ducts into the epididymis, vas deferens, seminal vesicles, ejaculatory duct

give an overview of female sex differentiation

• no presence of the SRY gene

• the primordial gonads differentiate into fetal ovaries

• this leads to an absence of AMH and absence of testosterone

  • the absence of AMH results in:

    • the transformation of the mullerian ducts into the: uterus, fallopian tubes, inner vagina

  • the absence of testosterone results in:

    • the regression of the wolffian ducts

    • the development of the: outer vagina, female external genitalia

what completes sexual differentiation and development?

puberty

what are the two major physiological processes involved in puberty?

1. adrenarche: a prepubertal increase in adrenal androgens at about 6-8 years of age that induces growth of pubic hair

2. gonadarche: physical and functional maturation of the gonads

what gonadotropins increase at the time of puberty to induce gonadarche?

LH and FSH

what are the secondary sex characteristics that develop?

• males: gonadarche results in the initiation and production of sperm, called spermarche

• females: gonadarche stimulates folliculogenesis and the initiation of the menstrual cycle, called menarche, and the development of breasts, called thelarche

what controls puberty?

hypothalamic secretion of Gonadotropin-releasing hormone (GnRH)

what do LH and FSH stimulate growth of?

the gonads and steroid hormone production

relative sensitivity of negative feedback regulation of hypothalamus-pituitary

go back to making this

what is spermatogenesis?

sperm production

define testes

a pair of male gonads where spermatogenesis occurs

when do the testes descend from the abdomen into the scrotum?

around the 7th month of gestation

what do sertoli and ledig cells promote and support?

spermatogenesis

define seminiferous tubules

sites of spermatogenesis

what do the rete testes and efferent ductules do?

pass the sperms to the epididymis

define epididymis

involves in storage and maturation of sperms

define vas deferens

large thick tube lines with smooth muscles that store and transport sperm to the ejaculatory duct

what is connected to the ejaculatory duct?

the urethra

what structures produce secretions that make up seminal fluid?

seminal vesicles, prostate glands, and bulbourethral glands

what does seminal fluid consist of?

• nutrients

• alkaline buffers

• chemicals to enhance sperm motility

• mucus

• prostaglandins

how do sertoli cells support spermatogenesis?

• provide developing sperm cells with nutrients

• secrete laminal fluid

• secrete paracrine factors to initiate and stimulate spermatogenesis

• secrete androgen-binding protein (ABP) that binds to testosterone, maintaining high levels of testosterone in the seminiferous tubules

• form blood-testis barrier, which prevents many chemicals and antibodies from the blood to enter the lumen of the seminiferous tubule

give a timeline of spermatogenesis

1. spermatogonia, germ cells, begin mitotic division in the seminiferous tubules at puberty

2. some spermatogonia also undergo differentiation to become primary spermatocytes

3. first meitotic division occurs reulting in secondary spermatocytes

4. second meitotic division generates spermatids

5. spermatids produce sperms that are released into seminiferous tubules

6. spermatozoa stored in the vas deferens

7. ejaculated, can live in vaginal 4-6 days

what is spermiogenesis?

when spermatids undergo a morphological transformation

what are spermatozoa?

mature sperm cells

what is require for the reproductive function of a male?

coordinated action of neuronal and endocrine systems

what happens in the hypothalamus and anterior pituitary pathway of male reproductive function?

• hypothalamus secretes GnRH intermittently

• the release of GnRH causes the anterior pituitary to secrete FSH and LH from gonadotroph cells

what is the effect of LH and FSH on the testes?

• LH stimulates Leydig cells to synthesize and secrete Testosterone

• FSH stimulates Sertoli cells to grow and secrete spermatogenic substances to support spermatogenesis

describe the feedback control of the male reproductive function

• testosterone inhibits GnRH secretion

• testosterone inhibits LH secretion from the anterior pituitary

• too little secretion of testosterone allows hypothalamus to increase GnRH secretion

• Sertoli cells secrete inhibin, which inhibits secretion of FSH from the anterior pituitary

what are the gonadal hormones in men?

testosterone, hihydrotestosterone, androstenedione

describe the pathway of the synthesis of androgens in the testes and 17beta estradiol formation

• cholesterol —> pregnenolone —> 17-hydroxypregnenolone —> DHEA —> androstenedione

  • androstenedione + aromatase —> estrone —> 17beta estradiol

• androstenedione —> testosterone

  • testosterone + aromatase —> 17beta estradiol

• testosterone —> dihydrotetosterone

describe the fate of secreted testosterone in males

• testosterone circulates the blood for 30-60 minutes then binds to cellular receptors or becomes inactivated

• in peripheral tissues, testosterone often converted to dihydrotestosterone by 5 alpha reductase

• testosterone is inactivated in the liver

  • liver converts testosterone into androsterone and dehydroepiandrosterone

• some testoserone is converted into estrogens

• it diffuses into target cells and binds to androgen receptors

what are the puberty and post-pubertal effects of androgen hormones?

• growth of male genitalia

• required for initiation and maintenance of spermatogenesis

• development of secondary sexual characteristics

• required for sex drive

• stimulates erythropoietin (EPO) secretion from renal cells

what are the male secondary sexual characteristics

• pattern of hair growth

• hypertrophy of the laryngeal mucosa and enlargement of the larynx

• increased thickness and ruggedness of skin

• muscle development

• bone growth, increase in size and strength

• elevated BMR

• increased RBCs

• slight increase in extracellular fluid volumes due to reabsorption of sodium

• inhibition of breast development

define ovaries

a pair of female gonads where oogenesis occurs

define oogenesis

ovum production

define ovarian follicle

promote and support oogenesis

define corpus luteum

transformed from ovarian follicle after release of oocyte from the ovary

define fallopian tubes

catch the released oocytes from the ovary by their fimbriae, move the egg by their cillia to the uterus

define uterus

hollow, thick-walled, muscular organ that supports development of embryo

define cervix

the end of the uterus

define vagina

a canal connecting the uterus to the female external genitalia

define oogonia

primitive germ cells

describe oogenesis and development of ovarian follicles

• during fetal development, oogonia undergo mitotic division to make more but lost that ability around the 7th month

• oogonia differentiate into primary oocyte

• oocytes are at meitotic arrest until puberty

• from puberty to menopause, selected number of primary oocytes are destined for ovulation success

  • one primary oocyte generates a secondary oocyte and a polar body

• when the secondary oocyte is in the fallopian tube after ovulation, the secondary oocyte occurs only when the secondary oocyte is fertilized by a sperm

  • one secondary oocyte generates one ovum and a polar body

give an overview of oogenesis and spermatogenesis

oogenesis:

• fetal development: oogonia —mitosis differentiation —> primary oocyte

• childhood: primary oocyte completes 1st meiotic division prior to ovulation

• puberty: secondary oocyte — 2nd meiotic division: completed after fertilization—> ovum

spermatogenesis:

• spermatogonia —mitosis differentiation—> primary spermatocytes —1st meiotic division—> secondary spermatocytes —2nd meiotic division—> spermatids —differentiation—> spermatozoa

explain follicular growth from birth to menstrual cycle and ovulation

• birth: all primary oocytes exist inside primordial follicles

• childhood: some of the primordial follicles grow into primary, preantral, and antral follicles

• each menstrual cycle: 10-25 antral and preantral follicles continue to grow and mature to become antral follicles

• ovulation: secondary oocyte is released from the graafian follicle to the fallopian tube and graafian follicle transforms to the corpus luteum

what is secreted by the corpus luteum?

estrogen, progesterone, inhibin

describe the selection process of follicles?

• only one antral follicle is selected during each menstrual cycle, known as the dominant follicle, to mature into a mature follicle, or graafian follicle, containing the secondary oocyte

• other unselected follicles undergo atresia (follicular degenderation/death)

describe the structure of an ovarian follicle

• oocyte is surrounded by Zona Pellucida

• granulosa cella and theca cells make up the outer layer

• larger follicles contain antrum a cavity containing follicular fluid

what do theca cells and granulosa cells produce?

estrogen

what does the antrum do in a large follicle?

creates a microenvironment that nourishes and supports oocytes

what are the two types of sex hormones that ovaries secrete?

• estrogens: beta-estradiol, estrone, and estriol

• progestogens: progesterone, 17-alpha-hydroxyprogesterone

how does the menstrual cycle affect the development of follicular growth?

• during the follicular phase, several follicles begin to develop but eventually one becomes dominant and is ovulated

• the dominant follicle secretes large amounts of estrogen

how does the menstrual cycle affect ovarian hormone synthesis?

• in luteal phase, the corpus luteum forms and begins to secrete large amounts of both estrogen and progesterone

• Theca cells secrete androgens, mainly androstenedione and testosterone

  • most of the androgens are converted by the granulosa cells into estrogen

how does the menstrual cycle also affect the morphology of the endometrium?

• proliferative phase: the estrogen from the ovarian follicles stimulate growth of endometrium and myometrium; blood vessels grow, cervix mucus thins

• secretory phase: progesterone maintains thickness of estrogen-primed uterine wall and stimulates growth and function of uterine glands. blood vessels continue to grow, cervix mucus thickens

  • creates an environment to support implanted embryo

• menstrual phase: low levels of estrogen and progesterone causes degeneration of the endometrium; blood vessels rupture (which causes menstruation)

the reproductive function of the female require coordinated action from what systems?

neuronal and endocrine systems

what happens in the hypothalamus and anterior pituitary of the female reproductive function?

• hypothalamus secretes GnRH

  • anterior pituitary secretes LH and FSH from gonadotroph cells

what effect do LH and FSH have on the ovaries?

• LH stimulates Theca cells to proliferate and synthesize and secrete androgens

• an LH surge triggers ovulation and transformation of the dominant follicle to corpus luteum, which secretes both estrogen and progesterone

• FSH stimulates Granulosa cells in the ovarian follicle to grow and secrete spermatogenic susbtances to support oogenesis

• FSH stimulates Granulosa cells to express aromatase to convert androgens released from the theca cells to estrogen

describe the feedback control of the hypothalamus and anterior pituitary during the early and middle follicular phases

• relatively low concentration of estrogen inhibits GnRH, FSH, and LH secretioins

• inhibin secretion inhibits FSH

• environment and psychological factors affect GnRH secretion

describe the changes to ovarian function and feedback regulations during the menstrual cycle

• early and middle follicular phases:

  • low plasma concentration of estrogen inhibit LH and FSH in response to GnRH

  • granulosa cells secrete inhibin, which inhibits secretion of FSH

• late follicular phase leading to ovulation:

  • positive feedback: dramatic increase in plasma estrogen during the pre-ovulatory phase stimulates the pituitary gland to secrete more LH and FSH

  • LH surge triggers ovulation

• luteal phase:

  • high plasma concentrations of progesterone, in the presence of estrogen, inhibits the secretion of GnRH

    • result: negative feedback inhibition of FSH and LH

  • inhibin produced by the corpus luteum inhibits FSH

describe the pathway for the synthesis of ovarian hormones

• cholesterol + increase of LH in theca cells —> pregnenolone

  • pregnenolone —> progesterone (only in the corpus luteum)

• pregnenolone —> 17-hydroxypregnenolone —> dehydroepiandrosterone —> androstenedione —> testosterone

  • testosterone + increase of FSH in granulosa cells + aromatase —> 17beta estradiol (main form of estrogen in females)

what are estrogens and progestogens synthesized from?

cholesterol

how do estrogens and progestogens travel in the blood?

they are bound to plasma albumin or specific binding proteins

what happens to estrogen and progesterone not taken up by target tissue?

• liver degrades them

• estrogen is secreted in the bile and/or excreted in urine

• progesterone is degraded and excreted in urine

what are the effects of estrogen?

• stimulates growth of ovary and follicles

• stimulates growth of smooth muscle and epithelial linings of reproductive tacts

• stimulates secretion of a clear cervical mucus

• stimulates external genitalia growth

• stimulates breast development

• stimulates female body configuration

• stimulates bone growth and closure of epiphysis, protecting against osteoporosis

• protects against atherosclerosis

• stimulates fluid retention

• stimulates prolactin secretion

what are the effects of progesterone?

• converts estrogen-primed endometrium to an actively secreting tissue suitable for embryo implantation

• induces thick, sticky cervical mucus

• decreases contractions of myometrium and uterine tubes

• decrease proliferation of vaginal epithelial cells

• stimulates breast growth

• inhibits milk producing effects of prolactin

define menarche

1st occurence of menstruation

when does secretion of gonadotropins begin and when do they slightly increase in females?

secretion begins at about 8 years and increases slightly until menarche

define thelarche

development of breast bud

when does premenopause take place?

starts from the onset of first menstrual cycle until menopause

when does perimenopause take place?

transitional period before menopause; irregular menstrual cycles and ovulation

what occurs during menopause?

• cessation of ovarian production of ova

• absence of menstrual cycles exceeds 12 months

• loss of ovarian estrogen and progesterone

• low estrogen levels

• dramatic increase in secretion of gonadotropins due to lack of negative feedback from ovarian hormones

• due to low estrogen, people in post menopause are at increased risk for osteoporosis and cardiovascular disease

why are hormonal changes critical during pregnancy?

critical to maintain pregnancy, provide fuel, promote blood flow, and prepare mother for lactation

what are the physiological demands of pregnancy?

increased cardiac output, increased blood volume, increased hematopoiesis (produced of red blood cells), increased tidal volume, and increased caloric demand for protein, folic acid, and iron

what is the source for HUman chorionic gonadotropic (hCG) and when is it secreted?

source: embryo (embryonic trophoblastic cells)

peaks 60-80 days after last menstruation and declines to low at 3 months

what eventually happen to embryonic trophoblastic cells?

eventually become part of the placenta

what is the function of hCG

• detection of hCG to confirm pregnancy in pregnancy test

• stimulates maternal ovaries to secrete gonadal steroid hormones which provide negative feedback to inhibit maternal LH and FSH secretion which prevent menstrual cycle

• keeps the corpus luteum alive

what produces/supplies progesterone?

• first 2 months is supplied by the corpus luteum

• then is produced by the placenta until parturition

define parurition

events leading to and including delivery of baby

what is the function of progesterone in females?

• inhibits contractility of the uterus so the fetus is not expelled

• progesterone in the presence of estrogen provides negative feedback to Hypothalamus and Anterior Pituitary (results in no ovarian or menstrual cycles during pregnancy)

• increase alveolar ventilation

what supplies/produces estrogen?

• first 2 months is supplied by the corpus luteum

• produced by the placenta until parturition

how does the placenta provide estrogen?

placenta relies on maternal ovaries, maternal and fetal adrenal gland to provide androgens needed to convert androgens to estrogen

what is the function of estrogen?

• stimulates growth of uterine mass

• participates in negative feedback to prevent menstrual cycles

what is the source of Human Placental Lactogen?

the placenta