CELL 305 -- unit 18 -- reproductive physiology

what are the male gonads

the testes

what is the function of the testes

produce sperm and testosterone

describe the anatomical build of the testes

divided into 250-300 lobes where there are seminiferous tubules able to transport stuff out (like sperm)

what are the two critical cell types of the testes

leydig and sertoli cells

describe leydig cells (function and where they are found)

- also known as interstitial cells

- produce sex hormones (testosterone and other androgens)

- found in the spaces between the seminiferous tubes

what are sertoli cells? where are they found?

epithelial cells found in the wall of the seminiferous tubules

what are the functions of sertoli cells

- nurture sperm and and control sperm development (help sperm mature)

- target cells of FSH and testosterone

- secrete inhibin

how do sertoli cells connect to neighboring cells? what does this allow for?

- tight junctions

- form the blood-testis barrier

- protects sperm from male's immune system

what is the function of the penis

press into the vagina to deposit sperm as close to the site of fertilization as possible

when and why does erection occur

the penis becomes erect during arousal because of erectile tissue

what is erectile tissue (of the penis)? what does it do?

- spongy connective tissue and smooth muscle

- capable of holding a large volume of blood

- increased volume and pressure produce swelling and elongation

what is the function of the scrotum

provides unique environment where testes are kept cooler than body temperature (ideal temp.)

- increased temperature suppresses sperm production

- suspends the testes outside the abdominal cavity

are testes one compartment or two

the testes are in separate compartments

What are the seminiferous tubules?

site of sperm production within the testes

what are the rete testis

short tubules formed by the convergence of the seminiferous tubules

what are efferent ductules

penetrate the fibrous coating of the testis and lead sperm to the exterior

what is the epididymis

- highly coiled duct loosely attached to testis's outer surface

- final site of sperm maturation (learn to swim)

- sperm stored here until ejaculation

What is the vas deferens?

- larger, muscular tube

- leaves the scrotum and enters the pelvic cavity

what is the ejaculatory duct

formed by the convergence of one vas deferens and the duct of one of the seminal vesicles

what are the 3 types of male accessory glands? what do they do?

1. seminal vesicles (two)

2. prostate gland (one)

3. bulbourethral glands (two)

they help the main pathway of sperm work

what are seminal vesicles? what do they do?

- two glands (one per vas deferens)

- produces 70% of seminal fluid (most of what is actually ejaculated)

characteristics and molecules included in the seminal fluid produced by seminal vesicles

- alkaline to neutralize acid in the vagina (keeps sperm alive)

- fructose to provide energy for sperm

- clotting proteins to facilitate clotting after ejaculation

- prostaglandins to suppress female immune response (tells female environment not to kill them)

what is the prostate gland

- one gland

- as all pathways converge to the urethra they will go through the prostate

- produces 25-30% of seminal fluid (contributes the rest of the ejaculate)

molecules included in the seminal fluid produced by prostate gland

contains citrate, zinc, and acid phosphates (minerals)

- functions not well established

prostate specific antigen (PSA)

- breaks down clotted semen to free sperm

- used as a prostate cancer marker

what are the bulbourethral glands

- two pea-sized glands

- close to the exit (penis)

- produce 'pre-ejaculate'

what is 'pre-ejaculate'

- viscous, sticky mucus

- serves as a lubricant

- cleans urethra prior to semen entering

* helps with insertion and sterilization

describe the pathway of the release of male reproductive hormones (order of release)

1. hypothalamus releases GnRH

2. gonadotropins come from the anterior pituitary (LH and FSH)

3.

- FSH acts on sertoli cells to stimulate spermatogenesis

- LH acts on leydig cells to trigger androgen secretion (lipophilic: diffuse to the rest of the testis, enter bloodstream)

describe the male reproductive hormone, testosterone

- promotes sperm production

- promotes development and growth of accessory reproductive organs during puberty (particularly relevant in utero development)

- maintains continued function in adult life

- development and maintenance of secondary sex characteristics (puberty)

- acts on the brain to promote the sex drive

what is the male gamete (sex cell)

spermatozoa (aka sperm)

describe the composition of spermatozoa

contain 23 chromosomes

- the 23rd chromosome is the sex chromosome

- can contain an x or y sex chromosome

- determine fetal gender

anatomy of a spermatozoa

1. head

- acromosome contains enzymes to allow fertilization to occur

2. midpiece

- anchors head to tail

- contains mitochondria (for energy)

3. tail

- flagellum

- propels sperm forward with whip-like motions

describe spermatogenesis

*because sperm is its own cell type it goes on its own division journey

*spermatozoa is its own population of cells

*each step = maturation of cells

1. spermatogonia undergoes mitosis and splits apart

2. spermatogonia then undergoes differentiation and becomes primary spermatocyte

3. undergoes meiosis I to become secondary spermatocytes (1 --> 2)

4. secondary spermatocytes undergo meiosis II and become spermatids (2 --> 4)

5. spermatids become spermatozoa

which way does spermatogenesis occur

- moves further and further into lumen to get captured into seminiferous tubules

- move tail first as they get released into tubules

what is the male sexual response at rest

- sympathetic NS dominates

- norepinephrine release at arterioles --> vasoconstriction

- Systemic vasoconstriction helps maintain normal blood pressure

what is the male sexual response during erection

- decreased SNS

- increased PNS input to arterioles

- PNS indices the increase of NO production (through signaling)

- nitric oxide (NO) release --> vasodilation --> filling of vascular compartments with blood --> erection

describe the physiology of metabolic infertility and erectile dysfunction (role of insulin in erectile function)

- nitric oxide (NO) is a potent vasodilator (necessary part of fertility and normal erectile function)

- Insulin plays a part in erectile functioning

Insulin sensitive state

- activation of the PNS induces the release of more insulin

- Insulin signals to blood vessels to create more NO which allows for vasodilation and normal erectile function

Insulin resistant state

- as the blood vessels become insulin resistant, Insulin is less capable of producing NO

- insulin-resistant endothelial cells fail to release nitric oxide

- Less NO = more vasoconstriction = more erectile dysfunction

characteristics of the female reproductive system

cyclic changes in activity (body's way of reassessing reproductive health each month)

- monthly cycle

- involves chemical and structural changes

restricted periods of fertility

- ova released one at a time

- period of fertility lasts only a few days

limited gamete production

what is the pathway of sperm

1. seminiferous tubules

2. rete testis

3. efferent ductules

4. epididymis

5. vas deferens

6. ejaculatory duct

7. urethra (actual exit)

gets sperm out to the female reproductive tract

describe the negative feedback system of the release of male sex hormones

1. hypothalamus releases GnRH

2. AP releases gonadotropes (LH and FSH)

LH

- LH acts on the leydig cells in the testis and tells it to produce testosterone

- testosterone elicits negative feedback and signals to the hypothalamus and gonadotropes of the AP to lessen their activity and reduce LH levels

FSH

- FSH acts on the sertoli cells to stimulate spermatogenesis and produce inhibin/sex-hormone binding protein/etc.

- Inhibin wants to turn things off, so it sends signals to the hypothalamus and AP to reduce activity

- at the same time, sertoli cells in response to FSH also produce sex-hormone binding globulin (protein that binds testosterone)

what is sex-hormone binding globulin

protein that binds testosterone; responsible for the bound pool

describe the ovaries

- slightly flattened oval structures

- one on either side of the uterus in the abdominal cavity

- full of follicles

what are follicles

- a single-developing egg (ovum) surrounded by a bunch of other cells

- increase in size and complexity during development

- eventually ruptures to release (the biggest) ovum (ovulation)

what three kinds of cells do follicles contain?

1. follicle cells

2. granulosa cells

3. theca cells

what do granulosa cells contained in follicles do

- analogous to sertoli cells

- respond to FSH and estrogen (sex hormone)

- secrete inhibin

- transport nutrients to developing eggs

what do theca cells contained in follicles do

- somewhat analogous to leydig cells

- produce androgens (earliest versions of the sex hormones) that are converted into estrogens by granulosa cells

what is the most important part of male fertility? female fertility?

spermatozoa

follicles (and ova in them)

describe the uterine tubes

- "fallopian tubes"

- about 10 cm long

- on each side of the uterus

- supporting and transporting the egg from the ovary to the uterus

- normal site of fertilization

how does the oviduct facilitate egg transportation

- fimbriae (finger-like projections on the ovary that allow oviduct to capture egg as it ruptures out of the ovary)

- ciliated epithelium (in actual tube; cilia gently pass egg down tubes from ovary to uterus)

- trip takes about four days

what is the uterus

- hollow, pear shaped structure (collapsed with nothing in it; not filled with air)

- houses and nourishes the growing fetus

- three layers thick

what are the three layers of the uterus

1. perimetrium: visceral layer of the peritoneum (outermost layer)

2. myometrium: smooth muscle layer

- thickest layer

- contracts during birth

3. endometrium: epithelial cells on connective tissue layer

- grows and thickens during the cycle

- provides nutritional support to the embryo

- sloughs off if fertilization doesn't occur (menses)

what is the cervix

- "neck" of the uterus

- narrow, little gap

- hundreds of glands produce mucus (consistency is affected by hormone levels and allows the sperm to move and fertilized egg to implant

what is the vagina

- 8-10 cm long canal

- outermost portion of female reproductive tract

- receives the penis

- acidic due to activity/presence of normal bacterial growth (this is a good thing!) (a little bit neutralized with ejaculate)

- prior to first copulation, opening is covered by a thin membrane called the hymen

what is oogenesis

development of the ova

describe the process of oogenesis

process begins during fetal development

- oogonia undergo mitosis

- begin first meiotic division, but stop during prophase (primary oocytes)

after puberty, and prior to ovulation, one primary oocyte resumes meiosis I every month (occurs in paused periods to delay development until it becomes more mature right before being released)

- results in secondary oocyte (what is released during ovulation into oviduct)

after fertilization the second meiotic division occurs

- results in ovum

what is the pathway of ova

1. ovaries

2. fallopian tubes

3. uterus (where fetus develops)

4. cervix

5. vagina

what is the menstrual cycle

repeated changes in the ovary and uterus through time

what are the two subcycles of the menstrual cycle

1. ovarian cycle

2. uterine cycle

menstrual cycle = net dynamic of all components (what happens at ovary and uterus)

what causes the menstrual cycle

caused by changes in estrogens and progesterone concentrations (sex hormones)

describe estrogens role in the ovarian cycle

- essential for ova maturation and release (ovulation)

- establishment of female secondary sexual characteristics (everything that makes her body a female body)

- essential for transport of sperm from vagina to fertilization site in oviduct (in part because of changes in endometrium as a result of estrogens)

- contributes to breast development in anticipation of lactation

describe progesterones role in the ovarian cycle

- important in preparing suitable environment in the uterus for nourishing a developing embryo/fetus

- contributes to breasts' ability to produce milk

- hormone of gestation (pregnancy)

what are the two phases of the ovarian cycle

1. follicular phase

ovulation in the middle of all phases

2. luteal phase

describe the follicular phase of the ovarian cycle

phase during which follicle matures (multiple are maturing, but only one will become the most mature and be ovulated)

- follicle: developing ovum and surrounding follicular cells

- menstruation (uterine cycle) --> ovulation

- lasts approximately 14 days

- estrogen dominated period of time

- no progesterone involved

describe the luteal phase of the ovarian cycle

marked by presence of corpus luteum (yellow body)

- corpus luteum develops from ruptured follicle

- ovulation --> before menstruation

- lasts approximately 14 days

- once follicle has released the ovum, the structure remains = the corpus luteum

- estrogen AND progesterone involved

describe the role of sex hormones in the follicular phase

- dominated by estrogen secretion

- theca and follicular cells function to secrete estrogen from the follicle

- rising LH levels (LH surge) leads to increasing estrogen secretion which is essential for maturation of ovum (where we start to have positive feedback where LH and estrogen start to play off each other resulting in huge peak)

- allows for maturation of ovum

describe the process of follicular maturation in the follicular phase

1. primordial follicle: follicle cells and the oocyte

2. primary follicle: oocyte and other cells like the theca cells and granulosa cells

3. secondary follicle: antrum develops

4. graafian follicle: antrum gets bigger

5. follicle ruptures and sends egg out (ovulation)

as follicle develops and gets bigger and bigger, fluid-filled area called antrum gets bigger too and balloons the follicle out until eventually it gets so big it bumps into edge of ovary and bursts egg out (ovulation)

describe the process of the corpus luteum after ovulation in the luteal phase

* follicle ruptures (ovulation)

1. corpus luteum degenerates

what day is ovulation

day 14 (middle)

how is ovulation controlled

- triggered by LH surge

- LH surge occurs because when estrogens reach a certain concentration it switches from an inhibitor (negative feedback) to a stimulator (positive feedback) of LH secretion

describe hormone regulation during early- to mid-follicular phase

- hypothalamus releases GnRH to AP

- AP releases the gonadotropes LH and FSH

LH

- LH stimulates the theca cells in the ovaries to produce estradiol

- estradiol inhibits hypothalamus and gonadotrope release from AP to turn stuff off (negative feedback)

FSH

- FSH signals to granulosa cells in the ovaries to produce/synthesize estradiol

- estradiol sends inhibitory signal to hypothalmus and AP to reduce the release of sex hormones

- FSH also stimulates the release of inhibin from granulosa cells

- inhibin sends direct inhibitory signals (negative feedback) to hypothalamus and AP

* FSH has a modest contribution to estradiol production, but a significant contribution to inhibin production

- FSH also stimulates granulosa cells to produce sex-hormone binding globulin/protein

* negative feedback of estradiol

hormone regulation during late follicular phase

- hypothalamus releases GnRH

- AP releases the gonadotropes LH and FSH

LH

- LH stimulates the theca cells in the ovaries to produce estradiol

- estradiol activates hypothalamus and gonadotrope release from AP (positive feedback)

FSH

- FSH stimulates the granulosa cells in the ovaries to produce estradiol

- estradiol activates hypothalamus and gonadotrope release from AP (positive feedback)

* positive feedback of estradiol (due to LH pumping, pumping, pumping---steady increase)

describe the role of sex hormones in the luteal phase

- marked by presence of corpus luteum ("yellow body")

- corpus luteum secretes progesterone and estrogens (luteal phase is dominated by progesterone)

- progesterone peak is responsible for inhibition of LH and FSH secretion (prevents new follicle maturation and ovulation)

- ^^^ essential check on ovulation to avoid hyperovulation

what does the luteal phase do

- prepares uterus for implantation of fertilized ovum (sex hormones help, particularly progesterone) (ovarian cycle contributes to uterine cycle)

- if fertilization does not occur, the corpus luteum degenerates

- after degeneration, the luteal phase is complete, follicular phase begins again

what are the three parts of the uterine cycle? How long/when do they occur?

1. menstrual phase: starts on day 1, lasts 3-5 days

2. proliferative phase: during the rest of the follicular phase

ovulation

3. secretory phase: during the luteal phase

connect the parts of the uterine cycle to parts of the ovarian cycle

1. (uterine cycle) menstrual phase: sloughing out your unoccupied endometrial lining = (ovarian cycle) follicular phase: early stages of follicular development

2. (uterine cycle) proliferative phase: endometrium begins building back up = (ovarian cycle) follicular phase: mid-late follicular development

3. ovulation: ovum is released from follicle into fallopian tube, into uterus

4. (uterine cycle) secretory phase: endometrium builds for implantation = (ovarian cycle) luteal phase: if fertilization does not occur, the corpus luteum degenerates

* if the corpus luteum degenerates, progesterone and any chance of gestation is gone so the phases start again. Next follicles start maturing as the endometrium is shed

what is the menstrual phase

discharge of blood (from ruptured blood vessels) and endometrial debris (what developed during previous cycle)

- decreased estrogen and progesterone

- increased uterine prostaglandin --> uterine contractions and vasoconstriction

- blood flow to tissue decreases

- tissues die and slough into vagina, causing menstrual flow

how long does menstruation last

lasts five to seven days after degeneration of corpus luteum

what is the proliferative phase

uterus prepares for fertilized ovum

- endometrial lining develops

- stimulated by estrogens (promotes development of endometrium: blood vessels increase and cells are growing)

what is the secretory phase

endometrium prepared for implantation

- blood supply increased

- glands enlarge and secrete glycogen-rich fluids (to fuel energetic needs of growing fertilized egg)

- cervical secretions are more sticky, forming a plug (to lock in fertilized egg)

when does the secretory phase end

when corpus luteum degenerates and there is no more progesterone/chance of gestation

what is the most common form of infertility in men? women?

men: erectile dysfunction

women: polycystic ovary syndrome (PCOS)

what defines PCOS

the meeting of 2 of 3 criteria of the rotterdam criteria

what are the 3 criteria of the rotterdam criteria

1. hyperandrogenism

- ovaries aren't finishing the full production of estrogens (ovaries aren't converting androgens into estrogens); too little estrogen (for the sake of ovulation) and too much androgens (testosterone) --> causes hirsutism (male-adjacent hair growth)

2. oligomenorrhea

- doesn't have frequent or normal menstrual cycles

3. polycystic ovaries

- lots of follicles grow, but because of the absence of an LH spike and estrogen surge, none ever dominate/get big enough to ovulate and so they accumulate over time and become lots of cysts

about what percentage of women have PCOS

about 15%

T or F: all estrogens were once androgens

true

relationship between insulin and PCOS in women

- PCOS is a disease of hyperinsulinemia

- MOST women with PCOS have confirmed insulin resistance (pre-diabetes) (all are treated with insulin-sensitizing medication like metformin)

what is insulins role in PCOS

- within the ovaries there is an enzyme called aromatase that converts androgens to estrogens

- insulin inhibits this enzymatic process and stimulates the androgen secretion by ovaries, meaning people who have hyperinsulinemia/insulin resistance have lots of androgens but not enough estrogens because they are not getting converted

- increases free testosterone and stimulates follicle development but NOT ovulation (not enough estrogen for estrogen spike needed for ovulation)

relationship between insulin and testosterone in women with PCOS

insulin increases testosterone release from theca cells by roughly 13x

basically, PCOS is a disease based on what 2 things

1) too much insulin eliciting... 2) not enough estrogens, thereby preventing normal ovulation

explain how the journey of an oocyte occurs (ovulation --> fertilization). how long does it take? what needs to happen within the journey for fertilization to occur?

1. at ovulation, fluid movement causes the secondary oocyte (from ruptured follicle in ovary) to enter the fimbriae of the uterine tube

2. peristaltic contractions move the secondary oocyte toward the uterus for several minutes

3. activity of cilia move the oocyte toward the uterus for a few days

- entire trip takes four days

- sperm must meet ovum during these four days (needs to go from edge of cervix through mucus-rich environment of uterus to oviduct)

explain the journey of sperm after sex. how long and how many sperm survive?

1. millions of sperm are deposited into vagina during copulation

2. sperm swim upstream (against cilia trying to push stuff out) to the uterus and uterine tube

3. survival time in reproductive tract is approximately five days

4. only a few hundred sperm reach the uterine tubes

explain the process of fertilization if the sperm reaches the oocyte

1. several sperm generally reach the ovum and try penetrating the corona radiata

2. when they get through/erode the corona radiata (because of enzymes on head), sperm bind to sperm-binding protein

3. enzymes break through the zona pellucida, allowing (one) sperm to access the oocyte

list the events of fertilization (oocyte --> zygote)

1. the first sperm to access the oocyte binds to a receptor on the oocyte plasma membrane

2. sperm transported into cytoplasm = fusion

3. sperm-binding proteins become inactivated and the zona pellucida hardens, preventing polyspermy

4. fusion stimulates second meiotic division of the oocyte (oocyte --> ovum)

5. sperm plasma membrane disintegrates

6. chromosomes from sperm and ovum migrate to center (23 from egg, 23 from sperm)

7. DNA replicated --> zygote

when does implantation occur

occurs 6-7 days post fertilization

what is responsible for implantation? why/how?

trophoblast:

- secretes enzymes (cytokines) that digest endometrial cells to provide nourishment for the embryo

- secretes paracrines that stimulate the decidual response

- infiltrates endometrial tissue to develop into the placenta (due to enzymes created by trophoblasts)

* initiate implantation and contribute to placenta formation

describe the formation of the placenta (why do we need it? what does it do? how?)

As the embryo grows, oxygen and nutrient demand (metabolic needs) increases

Placenta is the connection between mother and fetus

Projections called chorionic villi grow from the trophoblast into the endometrium

- endometrium is broken down

- fetal blood vessels are surrounded by maternal blood

- acts as the kidney, lung, and stomach (digestive tract) for baby -- bringing in and taking out nutrients/waste

- allows for exchange of stuff

explain weeks 5-10 of late embryonic development

week 5: heart, spinal cord, and GI tract start to develop

week 6: heart beating

week 8: lungs develop

week 9: remaining organs develop

week 10: size of a kidney bean = fetus

during pregnancy, what hormone does the placenta secrete

hCG (human chorionic gonadotropin)

hCG ensures:

- signals from placenta in uterus back into mom's circulation, telling ovaries we're pregnant so don't reset the menstrual cycle

- sustains corpus luteum

- corpus luteum secretes estrogens and progesterone during first two months of pregnancy

- placenta secretes estrogens and progesterone during remainder of pregnancy

- progesterone inhibits hypothalamic-pituitary-gonadal axis and GnRH, LH, and FSH release, preventing LH surge

- no follicles are developed or ovulated

- (birth control)

role of estrogens in pregnancy

- growth of duct tissue in the breasts

- prolactin secretion

- growth and enhanced contractile responsiveness of smooth muscle in uterus (oxytocin)

keep fetus developing/growing

role of progesterone in pregnancy

- growth of glandular tissue in the breasts

- maintenance of secretory-phase uterine conditions

- suppression of contractile activity of smooth muscle in uterus

maintains uterine conditions and helps breast tissue get ready for lactation