Figure 266

1
Figure 26-6
2
Male Reproduction -Testis

• Compartments
• Interstitial tissue - Site of steroidogenesis
• Vascularized
• Contains Leydig cells
• Seminiferous tubules - site of spermatogensis and
  sperm transport
• Avascular
• Contains Sertoli and Germ cells
• Figure 26 9

3
Testicular cell types

• Germ cells - spermatogenesis
• seminiferous tubules
• Requires 64 days in humans for maturation
• Rate is hormone-independent
• Yield is hormone-dependent
• During the later stages of development - male
  fetal gonads contains 3 x 105 germ cells
  (spermatogonia)/gonad.
• increases to 6 x 106 spermatogonia/testes at
  puberty - produce 2 x 108 spermatozoa per day.

4
Molecular Structure of LH and FSH
5
Figure 26-5
6
Spermatogenesis

• Spermatogonium figure 26 9e

Mitotic divisions
Resting cell and 3 active cells
Mitotic divisions
Type B spermatogonia
spermiogenesis
Mitotic divisions
spermatids
1o spermatocytes
Meiosis I
Meiosis II
2o spermatocytes
7
Spermiogenesis

• Spermatids become
• spermatozoa
• Condensation of chromatin
• Formation of acrosome
• Growth of tail
• Extrusion of cytoplasm
• spermatozoa sloughed off into the lumen of the SM
  through spermiation

8
Sperm Maturation vs Capacitation

• Sperm stored in the cauda epididymis are able to
  fertilize ova in vitro
• Ejaculated sperm can not fertilize ova in vitro
  unless they are first "capacitated"
• Mixing of sperm with seminal plasma "coats" the
  cell membrane
• quality of seminal plasma differs among males
• fertilizing capacity of sperm may be affected by
  the quality of the seminal fluid

9
Sperm vs Seminal Plasma vs Semen

• Seminal plasma is the collective term used to
  describe the media in which ejaculated sperm are
  suspended
• Seminal plasma is produced by the accessory sex
  glands
• Size and level of function of the various
  accessory sex glands will vary among species as
  will the composition of seminal fluid
• Accessory sex glands and their secretion are
  regulated by androgens
• See figure 26 3

10
Somatic cells

• Leydig cells - under influence of LH
• Synthesize testosterone and androstenedione
• Testosterone diffuses across basement membrane
  into seminiferous tubules
• Sertoli cells
• Required for maintainence of normal
  spermatogenesis
• Regulated by FSH

11
Sertoli cell function

• Maintain blood-testis barrier
• Phagocytosis of damaged cells
• Provide nourishment for developing sperm
• Maintain ionic composition of seminal fluid
• Target cell for hormonal regulation of
  spermatogenesis
• Synthesis of E from A
• Synthesis of specific proteins - ABP, inhibin

12
Figure 26-11
1 pulse /70-90 min.
13
Figure 26-7
14
Major Actions of Testosterone

• Regulation of GnRH pulse generator
• Required for
• differentiation of reproductive tract and
  external genitalia in utero
• Maturation at puberty (development of 2O sex
  characteristics)
• Maintenance of reproductive tract in adults
• spermatogenesis
• expression of male behavior
• Other non-reproductive effects
• Blood and muscle
• bone metabolism pubertal growth spurt

15
Androgens

• 97 bound in plasma to
• SBG - 42
• Albumin - 39
• Other plasma proteins - 16
• Metabolism of Testosterone is to
• DHT
• E
• Androstenedione to androsterone

16
Actions of androgens and metabolites

• Androstendione
• Required for growth of secondary sex structures
• DHT
• Required for fetal development of prostate, penis
  and scrotum
• Active in promoting sperm maturation transport
  in adult
• Synthesized by 5 a reductase in peripheral
  tissues
• Skin, prostate, seminal vesicles and liver

17

• Estrogens
• 60-75 converted in peripheral tissues
• provides selective feedback regulation on LH
• Synthesized by aromatase in
• Sertoli cells, brain, skin, fat and liver

18
Relative abundance of steroids in males and
females
19
Major Components of the Reproductive Female System

• Hypothalamus - Location of the GnRH pulse
  generator. Major site of steroid negative
  feedback.
• Progesterone exerts inhibitory effects on the
  pulsatile secretion of GnRH and these effects are
  increased by estradiol.
• In castrate animals there is approximately 1
  pulse of GnRH (and consequently LH) every 60
  minutes. This is slowed to about 1 pulse per 4-6
  hours during the luteal phase or following
  progesterone/estradiol treatment of castrated
  animals.

20

• Anterior Pituitary - Secretes LH, FSH and
  prolactin. LH and FSH are gonadotropins. These
  have a and b sub-units. The a sub-unit is the
  same for LH and FSH, while the b imparts
  biological specificity.
• Ovary - Serves both exocrine (release of the egg)
  and endocrine functions.
• Mullerian duct-derived structures - oviduct,
  uterus, cervix, anterior vagina
• External genitalia

21
Figure 26 13
22
GnRH pulse generator

• LH secretion is pulsatile in nature in response
  to GnRH
• The frequency of GnRH discharges is steroid
  dependent.
• Progesterone inhibits the GnRH pulse generator
  and during the luteal phase estradiol increases
  the effectiveness of progesterone.
• Actions of estrogen are complex. In the absence
  of progesterone, estradiol may increase the rate
  of GnRH release. Also, estradiol will induce the
  preovulatory surge of LH.

23
Progesterone Effects on the Pulse Generator

• slows the GnRH pulse generator
• does not act directly on the GnRH neuron
• dominant steroid during the luteal phase
• effectiveness is enhanced by estradiol

24
Effects of Estradiol on the Pulse Generator

• Potentiates action of progesterone
• Acts directly at the hypothalamus to accelerate
  GnRH pulse generator when P4 is absent
• Can also act at the level of the pituitary to
  inhibit LH pulse amplitude during the follicular
  phase

25
Ovarian Cell Types

• Germ cells - oogenesis
• Follicular somatic cells
• Luteal somatic cells

26
Germ Cells

• Full complement of oogonia formed in fetal
  development
• 6 million oogonia initially formed
• 2 million incorporated into primordial follicles
• 400,000 present at puberty
• 400 destined to ovulate - rest (99.9) undergo
  atresia

27
Stages of Follicular development

• Primordial follicle (begins in fetal development)
• Spindle cells (later become GC)
• Basal lamina
• Oocyte (entering meiosis)
• Primary follicle (can also begin in fetal dev.)
• Spindle cells become cuboidal granulosa cells
• Secondary follicle
• Several layers of granulosa cells
• Theca interna forms outside basal lamina
• Zona pellucida formed (mucopolysaccharide coat)

28
Stages of Follicular developmentcont.

• Antral follicle
• Granulosa cells extrude fluid
• Fluid coalesces into the antrum
• GC continue to proliferate and form multiple
  layers
• Theca externa forms
• Dominant follicle is picked
• Continued growth of antrum
• Rest undergo atresia

29
Ovulation

• Basal lamina undergoes proteolysis
• Antrum increase in size
• Theca bcomes further vascularized
• Follicle ruptures
• Oocyte extruded and completes Meiosis 1
• 1st Polar body formed
• If fertilized completes Meiosis II with 2nd polar
  body formed

30
Figure 26-14a
31
Figure 26-14b
32
Corpus Luteum formation

• Following ovulation the follicle differentiates
  into a corpus luteum
• Produces increasing amounts of progesterone
• Undergoes luteolysis after 14 days

33
Figure 26-14c
34
Figure 26-14d
35
Ovarian Cycle

• Follicular phase - Most variable phase of the
  cycle, in terms of length, in most individuals.
  Characterized by increasing estradiol secreted by
  the developing follicle. LH pulse frequency is
  about 1 pulse per hour and may exceed this
  slightly during the late follicular phase.
• Luteal phase - Characterized by by the growth
  and development of the corpus luteum and then
  full luteal function. In primates the CL produces
  both progesterone and estradiol.

36

• Ovulation - requires no external stimulus to
  initiate the LH surge. Increasing estradiol
  causes the LH surge, thought to act directly at
  the level of the anterior pituitary gland to
  cause LH release.

37
Human Menstrual Cycle

• Days 1-14 follicular phase (ovary) proliferative
  (uterus)
• Estrogen dominated
• Endometrium in proliferative phase
• Estrogen priming required for subsequent
  implantation

38

• LH surge
• Terminates E production
• Reinitiates meiosis
• Stimulates PG production for rupture
• Stimulates development of luteal cells
• Ovulation
• Days 15-28 Luteal phase/secretory
• Progesterone dominated
• Endometrium in secretory phase

39
Maternal Recognition of Pregnancy

• In non-fertile cycles CL regresses.
• Humans embryo secretes human chorionic
  gonadotropin (hCG). HCG has LH-like activity and
  maintains CL function.
• Once placenta is established it secretes
  Progesterone and corpus luteum no longer
  necessary

40
Physiological effects of ovarian steroids

• Estrogens
• Circulate bound 98
• 50 each to SBG and albumin
• Required for
• Follicular maturation
• Hyperplasia of uterus
• Synthesis of rec. for E and P in endometrium
• Feedback on hypothalamus and pit
• Prepubertal female - breast dev., maturation of
  external genitalia, fat distribution (female
  pattern)

41

• Progesterone
• Circulates 98 bound
• 50 each to CBG and albumin
• Required for
• Implantation
• Gland coiling glycogen secretion in endometrium
• Inhibition o uterine contractions and endometrial
  sloughing
• Negative feedback on hypothalamus and pit.
• Development of breast alveoli in prepub. Females

42
Sexual Differentiation

• chromosome sex - First level of differentiation.
  Heterogametic sex directs development. In mammals
  this is the male (XY)
• gonadal sex - ovaries develop from the cortex of
  the genital ridge and testis from the medulla of
  the genital ridge. Testis-determining factor
  (TDF/SRY) is thought to be the product of a
  single gene in the male embryo. See figure 24-4
• phenotypic sex - Development of the internal duct
  systems and external genitalia are determined by
  testicular secretion of several factors and
  enzymes within embryonic primordia.

43
Duct Development

• embryos have a pair of Mullerian and Wolffian
  ducts.
• Wolffian ducts (WD) develop into the epididymis,
  vas deferens and seminal vesicles in males.
• Testosterone reqd for normal development action
  is local.
• The embryonic testes secrete Mullerian inhibitory
  hormone (MIH) - inhibits the development of the
  Mullerian ducts.
• Female embryos lack testosterone and MIH
  resulting in atrophy of the WD and development of
  the Mullerian ducts into the oviduct, uterus,
  cervix and anterior vagina.

44
Figure 26-3 a
MIH
testosterone
45
External Genitalia
In the male, testosterone is locally metabolized
to dihydrotestosterone by 5- a reductase in
tissues that form the external genitalia. Genetic
defects in either the receptor for testosterone
or 5- a reductase will result in genetic males
which have external genitalia that resemble the
female this is called testicular feminization.
46
Figure 26-3b
Response to dihydrotestosterone
47
 Brain

• The brain is a sexually dimorphic organ.
• Testosterone is converted to estradiol within the
  hypothalamic tissues of the male and estradiol is
  the steroid responsible for directing the final
  stages of sexual differentiation of rodent
  brains.
• Administration of large amounts of testosterone
  or estradiol to other species also has been shown
  to alter the physical and functional status of
  neuronal tissues involved in reproduction.

48
Sexual Differentiation of the Hypothalamus

• functional correlates
• pattern of LH release in response to estradiol
• lordosis behavior