Reproduction

reproductive endocrine organs

• hypothalamus

• pituitary gland

• ovary

• testes

HPG axis

1. hypothalamus releases GnRH

2. anterior pituitary gland releases gonadotropins (FSH and LH)

3. gonads release sex steroid hormones

4. sex steroid hormones inhibit secretion and responsiveness to GnRH (negative feedback)

mitosis

produces diploid cells

meiosis

produces haploid cells

zygote

ovum is fertilized by sperm in Fallopian tube

testis-determining factor (TDF)

transcription factor located on Y-chromosome (SRY gene) that determines if testes will develop; occurs in the first 40 days following fertilization

X-chromosome inactivation

in females, one X-chromosome is inactivated

intersex

• reproductive or sexual anatomy does not fit typical definitions of male or female

• causes: reduced or loss of function in TDF, TDF translocation to X-chromosome, androgen insensitivity

placenta

formed by embryo after implantation in uterine wall

gestation

developmental milestones tracked across three trimesters

first trimester

• ~8 weeks

• external genitalia begin to emerge (determines sex)

  • male = testosterone or dihydrotestosterone (DHT) present

  • female = testosterone or DHT absent

second trimester

• weeks 13-25

• typical first movement (weeks 16-20)

• lungs start to produce surfactant (week 29)

third trimester

• weeks 13-25

• most organs developed

• weight gain

full term

38 weeks after conception

intersex females

• too much androgen exposure

• not enough Wnt4 exposure

• aromatase deficiency

• masculinization

intersex males

testicular feminization (ex: testosterone, testosterone receptors, problem with 5α-reductase)

puberty

• process of sexual maturation, triggered by high pulsatile LH

• females: > 8 years

• males: > 10 years

thelarche

start of breast development

menarche

first menstruation

menstrual cycle

drives maturation and release of oocyte about once a month

spermatogenesis

spermatogonia → spermatozoa in ~74 days

menopause

• ovarian follicles are depleted

• change/loss of hormones

• transition from high estrogen state to low estrogen state (hot flashes)

• loss of estrogen protection (heart, vasculature, bone mass)

hypogonadal

occurs in males by ~70 years

ovaries

produce oocytes and release estrogen and progesterone

Fallopian tubes

transport sperm to ovum and fertilized ovum to uterus

endometrium

• layer of glands and blood vessels lining uterus

• shed during menstruation

myometrium

• uterine smooth muscle

• contracts during child birth (parturition)

oogenesis

1. primary oocyte in immature follicle

2. FSH stimulates growth

3. secondary follicle (develops fluid vesicles)

4. meiosis → secondary oocyte + polar body

5. only one follicle matures to ovulation each cycle

6. LH causes mature (Graafian) follicle to rupture, releasing oocyte (ovulation)

7. if fertilized by sperm, second meiotic division occurs (zygote)

8. if no fertilization, corpus luteum degenerates and menstruation occurs

follicular phase

• days 1-13

• days 1-4 = menstruation

• days 5-13 = proliferative FSH, then estrogen

ovulation

• ~day 14

• LH surge

luteal phase

• days 15-28

• progesterone and estrogen from corpus luteum

• expansion of endometrial lining and glands

GnRH release

influenced by stress, emotion, and rigorous athletic activity (low body fat, decreased leptin)

amenorrhea

loss of menstruation

acrosome reaction

1. contact of acrosome (head of spermatozoa) to zona pellucida (ovum)

2. fusion occurs, exocytosis to release acrosome enzymes

3. inner acrosomal membrane fuses, enters ovum

4. creates calcium wave in ovum

5. in ovum, induction of second meiotic division and changes to block other sperm

6. now a zygote (diploid)

7. travels to uterus for implantation

human chorionic gonadotropin (hCG)

• mimics LH

• prevents menstruation

• maintains uterine lining for pregnancy until placenta secretion of progesterone

placental hormones

• hCG

• hCS

• progesterone

• estrogen

labor

stimulated by oxytocin and prostaglandins

childbirth

fetal CRH (from placenta), ACTH, and corticosteroids are important

lactation

1. suckling/baby’s cry

2. ascending sensory signal

3. hypothalamus

4. decreased dopamine

5. anterior pituitary

6. prolactin

7. milk production

8. posterior pituitary

9. oxytocin

10. milk ejection reflex

hormonal actions during pregnancy

• promote implantation

• dampen mother’s immune system (limit reaction to fetal antigens)

• myometrial quiescence (prevents mestruation)

  • hCG (first 8-10 weeks)

  • progesterone (by 8 weeks)

• parturition

estrogen (females)

• increases…

  • blood volume by 40% in third trimester

  • stroke volume by 30%

  • heart rate by 15%

  • tidal volume by 50%

  • renal blood flow by 40%

  • production of clotting proteins (late in pregnancy)

  • antibodies for passive immunity (IgG in late pregnancy, IgA after birth)

human chorionic somatomammotropin (hCS)

• opposes insulin which minimizes hypoglycemia to protect energy source for fetus

• increases lipolysis, FFA, glucose, and ketones

• burden on mother, increases susceptibility to gestational diabetes

preeclampsia-eclampsia

• pregnancy-induced hypertension, proteinuria, and edema

• common cause of maternal death

• treating hypertension may cause placental insufficiency

dysmenorrhea

• painful menstruation and cramping in lower abdomen

• primary: abnormally high prostaglandin production (endometrium) causes excessive contractions

• secondary: to pelvic disease (ex: endometriosis → extrauterine “ectopic” endometrial tissue)

• treatments reduce hormone fluctuations

abnormal vaginal bleeding

• structural lesions (ex: endometrial polyps)

• cancers (uterine, cervical, endometrial)

infertility

• inability to achieve pregnancy for > 1 year

• source can be either male or female

• ovarian dysfunction

• tubal or pelvic dysfunction (ex: endometrial scarring)

epididymis

sperm maturation

vas deferens

transports sperm from testes to urethra

prostate

secretes prostate fluid for semen

testes

• testosterone release and sperm production

• ~2°C below body temperature

semen

• male reproductive fluid

• suspension of spermatozoa

penis

• voids urine

• ejaculates semen

seminiferous tubules

• sertoli cells → respond to FSH

• site of spermatogenesis

• secretes inhibin → negative feedback to inhibit FSH release

interstitial tissue

• leydig cells → respond to LH

• secretes testosterone which stimulates meiosis of spermatogonia

estrogen (males)

• at least part of negative feedback

• bone mass

• fusion of epiphyseal plates (bone)

aromatase

converts testosterone into estradiol

spermatogenesis

1. spermatogonia (diploid)

2. mitosis → spermatogonia + primary spermatocyte

3. primary spermatocyte undergoes meiosis

4. after two meiotic divisions → four haploid spermatids

5. maturation of spermatids

   • develop flagellum

   • develop acrosome (cap with digestive enzymes for penetrating ovum)

6. transported to epididymis

   • flagellum matures, becomes motile

erectile tissue

• corpus cavernosa and corpus spongiosum

• during arousal, fills with blood, causing erection

• PNS activates nitric oxide release

• vasodilation of penile vasculature fills corpi

• pressure of corpi limit venous outflow, trapping blood

• SNS stimulates ejaculation (expulsion of semen from penis)

erectile dysfunction

• difficulty in developing or maintaining an erection

• treatment with PDE inhibitors (ex: sildenafil)

  • inhibits phosphodiesterase → reduces breakdown of cGMP → extends inhibition of calcium channel → extends relaxation

pre-testicular infertility

• abnormal hypothalamus (GnRH) or anterior pituitary (LH, FSH) function, typically genetic

• anabolic steroid use

testicular infertility

• varicocele (dilates scrotal veins) → abnormal temperature, blood flow impairs spermatogenesis

• chromosomal structure abnormalities → low or no sperm (ex: Klinefelter syndrome)

• toxins, smoking, or temperature

post-testicular infertility

ductal obstruction, caused by genetic abnormality, surgery, inflammation, or infection

benign prostatic hyperplasia

• non-malignant growth

• enlargement of prostate

• common with age

  • one-third of men over 65 years

• symptoms: compression of urethra (urinary retention), increased bladder pressure, painful urination, nocturia, difficulty starting urination

• treatments: relax bladder and prostate smooth muscle

  • α1-adrenergic receptors (ex: prazosin)

  • PDE5 inhibitors (ex: sildenafil)

  • 5α redcutase inhibitors (ex: finasteride)