Lecture 10, 11, & 12 - Endocrine, Reproduction 1-3

The REPRODUCTIVE System

Objectives:

The reproductive system consists of the gonads, reproductive tract, and accessory sex glands.

Reproduction depends on the ___ of male and female gametes.
->The reproductive systems of the two sexes are designed to enable this union.

•The female system is also equipped to house and nourish the ___ developmentally until it is able to survive on its own.

•___ reproductive organs produce gametes and secrete sex hormones:
->Male – __ (produce spermatozoa and secrete testosterone)
->Female - ovaries (produce ova and secrete estrogen and progesterone )

•A reproductive tract plus accessory ___ are found in either sex.

•Unique ___ sexual characteristics are found in each sex.
->Differences in body configuration and distribution of body hair.
->Due to ___ in male and ___ in female.

Functions and anatomy of the male reproductive tract:

•Production of ___ (_____)

•Delivery of ___ to the female

Functions and anatomy of the female reproductive tract:

•Production of ___

•Reception of ___

•___ of sperm and ova to a common site for union

•Maintenance of the developing ___

•Parturition

•Nourishing the infant

Reproductive cells each contain a HALF SET of chromosomes.

Gametogenesis occurs by ____.
–Cell division involves the division of the nucleus and the division of the ___.

–___ is cell division that maintains the chromosome number, chromosome combination, and genetic identity of the chromosomes from the dividing parent cell to the two daughter cells produced. Mitosis produces ___ cells.

–Meiosis produces ___. Only one chromosome from each chromosome pair is inherited in each of the four daughter cells produced from parent cells. The gametes have __-__ the chromosome number.

Male & Female sex determination
and sexual differentiation:

->Genetic sex depends on combination of ___ ____.

->Gonadal sex determined by presence or absence of ___ gene.

->Sex-determining region of Y
chromosome (SRY) codes for production of ___-___ ___ (__)

->NO Y chromosome = NO __ & ___

->TDF directs differentiation
of gonads into ____ .

->With no TDF, undifferentiated
gonads develop into ____ .

Male & Female sex determination
and sexual differentiation:

->Testes secret testosterone and ___ ___ ___ (__).

->Mullerian-inhibiting factor leads to degeneration of ___ ___ .
(this is in ___)

->Absence of Müllerian-Inhibiting factor leads to development of ___ ___ in females.

->Absence of testosterone leads to degeneration of ____ ___ .
(this is in ___)

->____ sex determined by presence or absence of masculinizing hormones.

External genitalia develops from the SAME embryonic tissue:

Genital Tubercle = ___ tissue
•Glans penis
•Glans clitoris

Urethral folds
•Fuse to form ___ in male
•Labia ___ in female

Genital swellings
•Fuse to form ___ and prepuce in males
•Labia ___ in females

*No dihydrotestosterone (DHT) = _____
*Presence of DHT = _____

Reproductive tracts develop from DIFFERENT embryonic tissues:

->Mullerian ducts and Wolffian ducts are present in ___ sexes before sexual differentiation.

Placental human chorionic gonadotropin stimulates:
->Testosterone – ___ Cells

->__ ___ ___ (__) – Sertoli Cells

*Testosterone → __Wolffian ducts
*MIF → ↓___ ducts

->Wolffian ducts differentiate into ___ reproductive tract

->Müllerian ducts differentiate into ___ reproductive tract.

ERRORS in sexual differentiation

•If testes fail to properly differentiate → anatomic ___, but genetic ___

•___ ____ ____ = Genetic males whose target cells lack androgen receptors are feminized even though adequate testosterone is secreted

•__-___ ___ = testosterone does not get converted to dihydrotestosterone (DHT) → genetic male with testes and male reproductive tract, but female genitalia

•___ ___ = genetically female fetus that oversecretes DHEA can cause differentiation of the reproductive tract and external genitalia along male lines

REVIEW

Male Reproductive Physiology

Testes develop from the ___ ridge in the rear of the abdominal cavity.

•During the last months of fetal life, the testes ___ from the abdominal cavity through the ___ canal into the scrotum. ->This movement is induced by ____ and usually complete by 7 months of gestation.

•Incomplete closure of canal or rupture leads to an inguinal ___.

•____ – undescended testicle(s) – bilateral or unilateral

•The scrotum provides a ___ environment that is optimal for spermatogenesis (which cannot occur at ___ ___. A spinal reflex by scrotal muscles can retract the testes into the warmer abdomen.

•The seminiferous tubules in the testis carry out _____.

•___ cells in the testis secrete testosterone. Located in interstitial tissue between seminiferous tubules.

Light micrograph of the

Semiiniferous Tubules

EFFECTS OF TESTOSTERONE

Prior to Birth:
•Masculinizes the Reproductive tract and external genitalia

•Causes ___ of the testes into scrotum

•Secretion ___ after birth

Effects on sex-specific tissues after birth (Puberty):

•Growth and maturation of the entire ___ reproductive system:
->___ = period of arousal and maturation of a previously nonfunctional reproductive system to the point of being able to reproduce
->____ = entire transition between childhood and adulthood, not just sexual maturation

•Spermatogenesis
•Accessory sex glands ___ and become active
•Penis and scrotum enlarge
•Maintenance of reproductive tract through adulthood

EFFECTS OF TESTOSTERONE

Other Reproduction Related Effects:

•Development of sexual libido
•Maintains sex ___ in adult male
•___ feedback control of ___ - ___ ___ (___) (and thus luteinizing hormone & follicle-stimulating hormone)

Effects on Secondary Sexual Characteristics:

•All SSC depends on ____
•Male pattern hair growth, deepening of the voice, thickening of the skin, male body configuration

Nonreproductive Actions of Testosterone:

•___ to protein

•Promotes bone growth

•Terminating bone growth (epiphyseal plate closure)

•May induce ____ behavior

Spermatogenesis:

the production and development of mature spermatozoa

The ___ ____ carry out spermatogenesis.

Anatomy of spermatozoa

Nucleus – ___ material

____ – enzymes, a modified lysosome produced by the endoplasmic reticulum-Golgi complex

Tail powered by ___ concentrated in the midpiece.

Cytoplasmic ___ b/w sperms cells during development allow necessary __ chromosome support for Y-bearing sperm.

SERTOLI Cell Functions

Throughout sperm cell maturation, the cells are intimately associated with ___ cells in the wall of the ___ ____.

The FUNCTIONS of the Sertoli cells:

•____ junctions provide a blood-testes barrier

•Prevent antibody formation against highly-differentiated spermatozoa

•Provide nourishment via selective transport of materials through the blood-lumen barrier. Glut-1 transports ___ across where it’s converted to ___ for use by the sperm

•Carry out ___ (engulf extruded cytoplasm, get rid of malformed germ cells)

•Secrete a seminiferous tubule fluid which flushes sperm from lumen to ___

•Secrete androgen binding protein (maintains high __ within lumen). High luminal __ is essential for sustaining sperm production. __ also stimulates ABP production

•Acted upon by testosterone and FSH to control ____, also secrete ___ to regulate FSH secretion

•Secrete ___-___ factor

Gonadotropin-Releasing Hormone (GnRH):

•increases at the time of ___

•Do NOT have receptors for ___ or ___

•___ neurons have receptors for androgens and estrogen

•Increases to cause puberty:
->__ increase initially
->Involves __ neurons
->Likely involves other neuron types as well

____ ____ Hormone:
– enhances spermatogenesis, needed for remodeling

____ Hormone:
– stimulates testosterone production from Leydig cells

_______:
-necessary for mitosis and meiosis

-___ selectively inhibits FSH secretion from Sertoli cell

Remainder of Male Reproductive System
Reproductive tract:

-Accessory sex glands
-Penis
**All geared toward delivering ____

Epididymis:
->______ = the gaining of the ability to move and fertilize

-Sperm are ____ of mobility or fertilization when they leave the testes.

-stimulation by _____.

-They gain further ability to do so in the ____ reproductive tract.

->_____ sperm 100x

Remainder of Male Reproductive System
Reproductive tract:

Ductus Deferens:

•STORAGE
->Sperm can be stored for up to 2 months due to low ____ needs

•Empties into the ____

•____ – ligation of the ductus or vas deferens

The male accessory sex glands contribute most to semen:

____: mixture of accessory sex gland secretions, sperm, and mucus

SEMINAL VESICLES:
–supplies ___ for energy (primary energy source)

–secretes ____ for smooth muscle contraction in the tract of both male & females (transport)

–provides most (about 60%) of the semen volume, washing the sperm into the urethra and diluting the thick mass of sperm, allowing ____

–secretes ___ (precursor of ___ needed for clotting, which keeps sperm in female reproductive tract)

The male accessory sex glands contribute most to semen:

_____ Gland:
–secretes an alkaline fluid to neutralize the acidity of the female reproductive tract to increase sperm viability

–provides clotting enzymes that act on fibrinogen to cause formation of ___

–Produces __ -___ ____ (PSA). This breaks down clot of sperm inside female reproductive tract, releasing sperm for ___. (Often measured as an index of potential cancer)

–___ ___ ___ = enlarged prostate in older men

–____ = vesicles that transfer components needed to maximize use of calcium for optimal motility and efficient fertilization

->____ Gland: Secretes a mucus-like substance for lubrication during sex

There are 4 phases to the male sexual response cycle:

1) _____ :
-erection
-testicular vasocongestion
-heightened sexual awareness

2) _____ :
-intensification
-steadily increasing heart rate, blood pressure, respiratory rate & muscle tension

3) _____ :
-ejaculation

4) ____ :
return of genitalia and body systems to their pre arousal state

Erection is accomplished by ____ of the penis with blood (____).

(____ = increased pooling of blood, decreased venous drainage)

Parasympathetic mediator – ___ ___

Erectile ____ (Impotence)
-50% ages 40-70
-70% by age 70

Nitric Oxide -> Guanylate cyclase -> PDE5 cGMP breakdown -> Smooth muscle relaxation -> vasodilation

-____ inhibits PDE5 cGMP breakdown

**Parasympathetic supply to penile arterioles causes penile arterioles to ____, which leads to an erection (compressed veins).

**NO used by PNS as a ____

Ejaculation is the emission and expulsion of semen:

Accomplished by a spinal ___

Occurs in two phases:

1) ___ – sympathetic impulses cause smooth muscle contractions in prostate, reproductive ducts, and seminal vesicles, thus delivering semen into the ___

2) ____ - the expelling of the semen through the urethra. Filling of urethra triggers skeletal muscle ____ at base of penis.

->Female sexual cycle is similar except there is no counterpart to ejaculation and no ____ following orgasm

•____ – Heavy breathing, high heart rate, generalized skeletal muscle contraction, intense pleasure & gratification

•Resolution follows, including a refractory period of varying lengths, due to increased ___ input

->Average volume – 2.75 ml of 165 million sperm (<__ ___/ml - clinically infertile)

REVIEW

FEMALE REPRODUCTION

Objectives

General Male-Female Differences

->Unlike males, where sperm production is continuous and testosterone is relatively stable, release of ova is ___ & hormones display wide cycle-associated ___ in the female.

•Menstrual cycle (menstruus = ___)

->Ovaries perform the dual function of producing ___ and secreting the female sex hormones (___, ___).

•Like males, reproductive capability begins at ____

•Unlike males, it does NOT continue throughout life (____)

By month 5 of gestation – 6 to 7 million ___

-Remain ___ oocytes from birth to puberty

-Oocytes not incorporated into follicles undergo ____

-By birth – 2 million primary ___

-By puberty – 300,000 (primary follicles)

-__ will mature and release ova

-___ = degenerated follicle (99.97%)

Follicular phase about 14 days

Luteal phase about 14 days

1) LH stimulates the ___ cells in the ovarian follicle.

2) On stimulation, the thecal cells convert cholesterol into ___.

3) Androgen diffuses from the thecal cells to the adjacent ___ cells.

4) FSH stimulates the ____ cells in the ovarian follicle.

5) On stimulation, the granulosa cells convert androgen into ___.

6a) Part of the estrogen is secreted into the ___, where it exerts systemic effects.

6b) Part of the estrogen remains within the ___ and contributes to ___ formation.

7) Local estrogen, along with __, stimulates proliferation of the ____ cells.

FOLLICULAR PHASE

Estrogen and inhibin, through actions at the pituitary, COMBINE to reduce ___-___ hormone secretion

Estrogen NOT capable of fully suppressing ___ hormone release

->Kisspeptin neurons in the ___ ____ of the hypothalamus are targeted by ____ feedback

Tonic secretion (___ & graded secretion)

SURGE Secretion

GnRH surge:
•Stimulated by high ___ levels

•Estrogen acts upon ___ kisspeptin neurons to stimulate gonadotropin-releasing hormone (GnRH) secretion

•Estrogen acts upon the ___ pituitary to increase ____ hormone as well (relatively less for follicle-stimulating hormone)

•____ still inhibiting follicle-stimulating hormone but there is a follicle-stimulating hormone surge as well

Luteinizing Hormone Surge:

1. ___ estrogen synthesis

2. Reinitiates ___

3. Triggers ___ release leading to rupture of cell wall

4. Conversion of follicular cells to ___ cell

LUTEAL PHASE

Luteal Phase

•Corpus luteum maintained by ___ hormone

•Lots of ___ produced, less estrogen

•Progesterone BLOCKS any positive effects of ____ on gonadotropin-releasing hormone secretion

•_____ a very powerful inhibitor of gonadotropin-releasing hormone/___ hormone release

•Factors underlying the demise of the corpus luteum are NOT completely known, but may involve prostaglandins, estradiol, and ___ LH secretion

*Tonic secretion (slow & ___ secretion)

1 to 5, 24
•Antrum formation, ___ secreted in response to follicle-stimulating hormone and luteinizing hormone.
•Rising ___ stimulates thickening of the endometrium.

6 to 8
•Circulating and antral concentrations of estradiol rise due to increasing levels of ___ hormone.
•Estrogen and inhibin actions at the pituitary selectively lead to a decline in ___ -___ hormone.
•Decline in follicle-stimulating hormone leads to ___ in all but the dominant follicle

9 to 11
•Rising estradiol triggers the ___ -____ hormone/____ hormone surge, causing ovulation and ___ levels to plummet.

12 to 17, 25

•Follicular cells are transformed to luteal cells and secrete ____ and, to a lesser extent, estradiol.
•Progesterone strongly inhibits BOTH ___ hormone and ___-___ hormone.
•Progesterone stimulates ___ vascularization and secretory activity of the endometrium.

18 to 23
•If NOT impregnated, the ___ ___ degenerates and progesterone and estradiol ___, allowing for an increase in ____ hormone and ___-___ hormone to begin the cycle again.
•Withdrawal of progesterone & estradiol leads to ___ off of the uterine endometrium.

Changes in the uterus (menstrual cycle) occur with changes in ovarian hormones:

•Estrogen stimulates ___ and myometrial growth.
(Also stimulates ___ receptor expression in endometrium.)

•Progesterone can then act on the estrogen-primed endometrium.

–Lining becomes ___ and edematous due to accumulation of water and electrolytes

–Stimulates endometrial glands to secrete and store ___

–Causes tremendous growth of endometrial ___ ___

–Reduces ____ of the uterus

Changes in the uterus (menstrual cycle) occur with changes in ovarian hormones:

MENSTRUAL PHASE
−Characterized by ___ of blood and endometrium

−Drop in hormone levels increases ___ release and ____ (and lack of O2) to the lining

−PG also stimulates uterine ___.
Prostaglandin ___production causes menstrual ____ (dysmenorrhea)

−Blood clots in uterus then is broken down by ___ to flow out.
−Contains large numbers of leukocytes (white blood cells) that play a role in helping the raw endometrium resist infection
−Lasts about 5-7 days, concurrent with early ___ phase

PROLIFERATIVE PHASE
−Endometrium repairs itself and starts to proliferate due to ___ __ and ___ ___ hormone
-induced estrogen secretion
−Estrogen stimulates epithelium, glands, blood vessels

SECRETORY/PROGESTATIONAL PHASE
−After ovulation when a new corpus luteum is formed (luteal phase)

−Corpus Luteum secretes large amounts of ___ & ____

−Progestational secretion of ___ into uterine lumen for nourishment of embryo

Cyclical Changes in Cervical MUCUS:

FOLLICULAR phase

−Under the influence of ___, cervical mucus is clear, thin, and abundant
−Most obvious when estrogen is highest (near ovulation)
−Facilitates passage of ___ through the cervical canal

•LUTEAL Phase

−Mucus becomes thick and sticky
−Essentially __ __ the cervical opening
−This prevents ____ from entering the uterus from the vagina
−Prevents sperm ___

PUBERTY

−Changes are similar to those in males.

−___ secretion increases at the onset of puberty.

−GnRH stimulates the release of ___ hormone from the anterior pituitary, first occurring at ___ .

−Doesn’t involve ___. The role of ___ is at least permissive.

−____ release promotes many changes in the female reproductive system and in other body characteristics (fat deposition in breasts, buttocks and thighs) & eventually the preovulatory surge.
(Also closes ____ ___).

−Growth of axillary and pubic hair, pubertal growth spurt, development of libido due to increase in adrenal ____

MENOPAUSE

−Unique to females

−May involve depletion of ___, may involve hypothalamic dysfunction

−Preceded by a period of increasingly ___ cycles and ___ estrogen levels (climacteric or perimenopausal period)

−Potential ____

−Hot flashes, may be due to increased ___ ___ secretion at surface vessels

Fertilization normally occurs in the __ __ of the oviduct (___).

•Fertilization must occur within __ hours after ovulation. If not, the ovum ___.

•Sperm cells normally survive for ~ _ days in the female reproductive tract, but can last up to _. (Sperm deposited from 5 days prior to 24 hrs after ovulation may fertilize ova)

•___ pregnancy can occur when it doesn’t enter the oviduct or stays in oviduct

Sperm migration is aided by the female tract/ovum:

−____ of cervical mucus (due to high ___ near the time of ovulation) allows passage into the uterus. Sperm get through cervix under their own ___.

−contractions of the uterine myometrium (smooth muscle layer) distribute sperm throughout ___ lumen. Stimulated by high ___ and seminal ___

−____ contractions of the oviduct (induced by estrogen and prostaglandins) propel sperm to site of fertilization, fimbriae (cilia) in oviduct

Sperm migration is aided by the female tract/ovum.

-hOR17-4, ___ receptor on sperm that is attracted to ____, a chemoattractant produced by the corona radiata.

-Binding increases intracellular ___ release, allowing for increased swimming.

−____ released by cells around the ovum also serve as a chemoattractant. It binds to surface membrane receptors and opens calcium-permeable cation channels (___) in the ___ of the sperm.

->Increase in calcium causes:
1. ____ of sperm
2. Hyperactivated ____ which provides sperm with increased power needed to penetrate the corona radiata and zona pellucida
3. ___ reaction

REVIEW

->_____ from corpus luteum stimulates glycogen release from endometrium and ____ oviduct allowing for zygote to be expelled into ___ lumen

->Time allows for necessary nutrients to accumulate in uterine ____

->____ and uterine lining become “sticky” through expression of cell adhesion molecules

->_____ makes a hole via enzymatic breakdown, but also makes nutrients available for blastocyst

->Area of uterus that undergoes changes to accept blastocyst = _____
-Local ____ release increases vascularity, causes edema, and enhances nutrient storage

Acceptance of Fetus by Mother; fetus is actually a FOREIGN object

___ natural killer cells are unable to kill fetal cells (unlike the usual natural killer cells)
->lock decidual dendritic cells in a ___ producing state
->dNK’s and DDC’s induce apoptosis of maternal __ _ cells
->promote production of regulatory T cells

•____ cells produce a unique Class 1 MHC glycoprotein that allows them to evade interaction with killer cells

•Trophoblastic cells produce ___ ligand
->Binds fas
->Fas is a specialized receptor on the surface of activated maternal ___ _ cells (immune cells that destroy foreign cells)
->Binding triggers ___ of T cells

•Fetal portion of placenta produces indoleamine 2,3 dioxygenase (___):
->Destroys ____
->Tryptophan is critical for ___ of cytotoxic T cells

•Production of ___ T cells is doubled or tripled
->____ T cells ___ cytotoxic T cells

The placenta is the organ of exchange b/w the maternal and fetal blood.

•Glycogen from endometrium is sufficient only for a ___ weeks

•___ – begins when trophoblast layer is 2-cells thick.

•As chorion ____, it forms cavities within ___ into which maternal blood leaks. Blood is kept from clotting via an ____ produced by the chorion.

•Fingerlike projections of the chorionic tissue form placental ___ that extend into these pools of maternal blood.

•Fetal ___ project into the placental villi. Fetal and maternal blood are separated here by a thin ___ layer.

•Exchange occurs b/w the maternal and fetal blood.

•Fetal blood leaves through an ___ vein.

•Maternal blood exits through maternal ____.

In place & operational by __ weeks after implantation

Functions of the Placenta

•Digestion, Respiration, Kidneys:
->Nutrients and __ move from maternal blood to fetus
->___ and other metabolic wastes move from fetus to maternal blood

•Different substances cross in different ways:
->simple diffusion, facilitated diffusion, secondary active transport, receptor-mediated endocytosis

•Many unwanted substances can also cross
->_____ = tranquilizer that caused limbless babies
->Heroin and other drugs lead to addicted babies
->Aspirin, alcohol, agents in cigarette smoke
->AIDS virus

•Placenta is also an ____ organ

•Human chorionic gonadotropin (__) maintains the ___ ___ of pregnancy by acting in the place of ___ hormone.

•Normal ___ hormone secretion reduced by continuing ___ secretion.

•Human chorionic gonadotropin stimulates ___ ___ production of testosterone in the male fetus.

•Human chorionic gonadotropin (HCG) eliminated in the ___ and forms the basis for early detection of ___ (about two weeks following missed menstrual period).

->Estrogen not produced by placenta __ on because it lacks the enzymes needed to make it and thus has to wait on the fetal adrenal to develop the ability to produce ___.

-Major estrogen produced is ___, which can only be produced from fetal ___, so estriol in mother’s urine can be used as an index of fetal viability

Lack of early progesterone production due to ___ mass of placenta

Estrogen:
1. Grows the ___
2. Promotes development of ducts in mammary glands

Progesterone:
3. Prevent ___ by suppressing myometrial contractions
4. Promotes __ formation in cervix
5. Stimulates the development of milk glands

Changes in later gestation prepare for parturition.

*Parturition is ___. During the last trimester the uterus becomes more excitable. Mild contractions occur (___-___ contractions).

•The cervix begins to soften near parturition due at least in part to the effects of ___.

•The fetus shifts downward, with its head contacting the cervix.

•Rhythmic contractions begin at the onset of ___. There are high levels of ___ at this time.
->Estrogen increases connexons within uterine smooth muscle cells. Form ___ junctions b/w cells that allow them to be electrically linked for coordinated contractions
->Estrogen increases myometrial receptors for ____.
->Estrogen stimulates increased local ____ production to promote cervical ripening (degradation of ___). These prostaglandins also increase uterine responsiveness to ___.

•Factors triggering the onset of parturition are not well understood.

PARTUITION DIAGRAM

Uterine Involution:
->Return of the uterus to ____ state (4-6 weeks)

->Due to loss of ___ and ___ support

->Breast feeding hastens process due to release of ___ that causes uterine ____

1.) First stage of labor Cervical ____
2.) Second stage of labor: ___ of baby
3.) Third stage of labor:Delivery of ____

•Milk synthesized in ___ epithelial cells, secreted into the alveolar lumen, and ejected into a milk duct that leads to the nipple

•Estrogen promotes ___ development

•____ promotes alveolar-lobule development

•Prolactin and human ___ ______ (__) induce synthesis of enzymes for making milk & also promote growth of the fetus through stimulation of IGF-1 & IGF-2

->Breasts are capable of lactation by ___ through pregnancy. High ___ and P block prolactin from causing milk release. Thus, the drop in E and P initiate lactation.

SUCKLING REFLEXES

Advantages of Breast Feeding:

For the infant:
-Nutrients (water, fat, lactose, proteins, vitamins, Ca2+, PO4)
-Contains a host of immune cells (particularly the ___ – milk produced in the first 5 days)
-Secretory __ = protect against infectious microbes that the infant is most likely to encounter
-___ : may bind to and prevent uptake of harmful microorganisms through the intestinal wall
-___ = decreases availability of iron to harmful bacteria
-Bifidus factor = promotes growth of lactobacillus bifidus, which helps crowd out harmful bacteria
-Other factors promote maturation of the digestive tract

For the mother:
->Hastening of uterine involution
->Suppression of menstrual cycle (perhaps through prolactin)

*Milk production stops at weaning due to the lack of ___ stimulation.

REVIEW