Module 4 - Reproduction Flashcards

1
Q

What does the ovary contain

A
  • stromal matrix
    (connective tissue,
    nerves, lymphatic and
    blood vessels)
  • follicles
  • tunica albuginea
  • surface epithelium
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2
Q

List the stages of Ovarian Follicles during Folliculogenesis

A
  1. primordial follicles (non-growing)
  2. preantral follicles (early growing)
  3. early antral follicles
  4. antral follicles
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3
Q

Describe Primordial to preantral
stages:

A
  • Gonadotropin INDEPENDENT i.e. no exogenous factors
  • Intraovarian/paracrine factors
  • Balance of stimulatory (activation/recruitment) and
    inhibitory (quiescence/apoptosis) factors
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4
Q

Describe Early antral and beyond stage

A
  • Gonadotropin DEPENDENT i.e. FSH and LH
  • Follicle cells acquire FSHR and LHR
  • Dominant follicle is selected
  • Some regulation by intra-ovarian factors (inhibin and activin)
    ➢ via +ve and –ve feedback loops
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5
Q

When does the preantral stage occur in the menstrual cycle

A

Throughout

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6
Q

When does the very early antral stage occur in the menstrual cycle

A

throughout

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7
Q

When does the early antral stage occur in the menstrual cycle

A

1-6

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8
Q

When does the expanding antral stage occur in the menstrual cycle

A

6-10

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9
Q

When does the expanded antral stage occur in the menstrual cycle

A

10-12

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9
Q

When does the preovulatory stage occur in the menstrual cycle

A

13-14

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10
Q

Overview of meiosis

A

Prophase I
Metaphase I
Anaphase I
Telaphase I
Prophase II
Metaphase II
Anaphase II
Telaphase II

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11
Q

Define meiosis

A

Meiosis is a type of cell division that occurs in sexually reproducing organisms and reduces the number of chromosomes in gametes (the sex cells, or egg and sperm).

  • During meiosis, the four daughter cells produced are haploid, meaning they only have half the number of chromosomes of the parent cell
  • Meiosis produces our sex cells or gametes (eggs in females and sperm in males)
  • Meiosis II is an equational division analogous to mitosis, in which the sister chromatids are segregated, creating four haploid daughter cells
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12
Q

FOLLICULOGENESIS

A

growth and
development of the follicle. it accompanies and supports oogenesis

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13
Q

OOGENESIS

A

growth and maturation of
the oocyte

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14
Q

Events of oogensis

A
  1. Before birth EVENTS
    At birth, all
    primordial follicles
    are already present
    and contain primary
    oocytes arrested in
    prophase I.
  2. Throughout life
    until menopause
    Primordial follicles
    begin to grow and
    develop. (Before
    puberty all
    developing follicles
    undergo atresia.)
  3. From puberty to
    menopause
    After puberty, some
    antral follicles are
    rescued from atresia
    each month and the
    primary oocyte in one
    (the dominant follicle)
    completes meiosis I.
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15
Q

Regulation of the ovarian cycle

A
  1. GnRH stimulates FSH and LH secretion
  2. FSH and LH stimulate follicles to grow,
    mature and produce steroid hormones
    2-cell 2 gonadotropin hypothesis
  3. Negative feedback inhibits gonadotropin
    release
  4. Positive feedback stimulates
    gonadotropin release
    - Estrogen levels continue to rise as a result
    of continued release by dominant follicle
    - When levels reach a critical high value, a
    brief positive feedback occurs on brain and
    anterior pituitary
    - Triggers LH surge
  5. LH surge triggers ovulation and formation
    of the corpus luteum
    - LH surge triggers primary oocyte to
    complete meiosis I to become the secondary
    oocyte
    - Secondary oocyte enters meiosis II and
    arrests at metaphase II
    - Shortly after ovulation:
    Estrogen levels decline
    LH transforms ruptured follicle into corpus
    luteum
    LH stimulates corpus luteum to secrete
    progesterone (and some estrogen)
    almost immediately
  6. Negative feedback inhibits LH and FSH
    release
    - Negative feedback from rising plasma
    progesterone and estrogen levels
    - Inhibin enhances inhibitory effect
    - Declining LH inhibits follicle development
    - If no fertilisation occurs:
    * Corpus luteum degenerates
    * Sharp decrease in progesterone and
    estrogen
    * Ends the negative feedback and cycle
    starts again
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16
Q

The uterine (menstrual) cycle

A

Cyclic changes in the endometrium that occur in response to fluctuating ovarian hormone levels

Three phases:
1. Days 1–5: menstrual phase
2. Days 6–14: proliferative (preovulatory) phase
3. Days 15–28: secretory (postovulatory) phase

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17
Q

Days 1–5: menstrual phase

A
  • Gonadotropin levels beginning to rise
  • By day 5, growing follicles starting to
    produce more estrogen
  • Functional layer of the endometrium shed
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18
Q

Days 6-14: proliferative phase

A
  • LH steadily rising with surge just before
    ovulation
  • FSH declining with increase just before
    ovulation
  • Rising estrogen levels → regeneration of
    the functional layer of the endometrium
  • Ovulation at end of the proliferative phase
    on day 14.
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19
Q

Days 15-28: secretory phase

A
  • Begins immediately after ovulation
  • Most consistent in duration
  • Drop in LH, but level still high enough to
    support progesterone (P) production by
    corpus luteum
  • P promotes well-developed blood supply
    and endometrial glands provide nutrientrich secretions to prepare for implantation
  • P thickens cervical mucus to form a plug
    that blocks entry of more sperm,
    pathogens or debris
  • If corpus luteum degenerates, P causes
    spiral arteries in endometrium to constrict
    and endometrial tissue dies
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20
Q

why does the female cycle have 2 phases

A

The two phases of the female cycle are necessary for the preparation of the uterus for pregnancy and the release of an egg for fertilization. The follicular phase prepares the egg for release, while the luteal phase prepares the uterus for implantation of a fertilized egg.

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21
Q

Identify some actions of estrogen and progesterone on reproductive
organs

A
  1. stimulate growth and maturation of reproductive organs and breasts and maintain their adult size and function
  2. promote the proliferative phase of menstrual cycle
  3. stimulate production of watery cervical mucus and activity of fimbriae and uterine tube cilia
  4. promote oogensis and ovulation
  5. during pregnancy, stimulate growth of uterus and enlargement of external genitalia and mammary glands
  6. metabolic effects
  7. neutral effects
  8. promotion of secondary sex characteristics
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22
Q

Define progesterone

A

Progesterone is a hormone that plays an important role in the menstrual cycle, pregnancy, and embryogenesis of humans and other species

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23
Q

Define estrogen

A

Estrogen is a group of hormones that play an important role in the sexual and reproductive development in women.

Estrogen is responsible for developing female sexual characteristics, including breast development, growth of pubic and underarm hair, and the start of menstrual cycles.

Estrogen is produced by the ovaries, adrenal glands, and fat tissues

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24
Q

True or false: Men do not have estrogen

A

False - they do have estrogen but in smaller amounts.

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25
Q

Testis migration during development

A

10-15 weeks
- Pelvic position
- Suspensory ligament
lengthens and
regresses
25-28 weeks
- Migrates over pubic
bone
- Reaches scrotum by
35-40 weeks

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26
Q

identify and describe the 2 functional compartments of the testis

A

The intratubular compartment:
- seminiferous tubules
- lined with complex stratified
germinal epithelium
- contains sperm cells and sertoli cells
- Sperm production

The peritubular:
- neuronal and vascular elements
- connective tissue, immune cells,
interstitial Leydig cells
- Steroid (androgen) production

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27
Q

Function of testis

A

Sperm and steroid hormone production

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28
Q

Leydig cells

A

(interstitial cells) =
steroidogenic
(cf theca cells in females)
-synthesize and secrete androgens (testicular hormones).

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29
Q

Summary of events in Spermatogenesis

A
  1. Mitotis
    - produces large numbers of cells
  2. Meiosis
    - generates genetic diversity and ½
    chromosomes
  3. Spermiogenesis (Cytodifferentation)
    - packages the chromosomes for effective
    delivery to the oocyte
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30
Q

Hormonal regulation of testis by HPG

A
  1. The hypothalamus releases GnRH,
    which reaches the anterior pituitary
    via the hypophyseal portal veins.
  2. GnRH causes anterior pituitary
    gonadotropic cells to release FSH
    and LH.
  3. FSH indirectly stimulates
    spermatogenesis by causing
    Sertoli cells to release ABP, which
    keeps the local concentration of
    testosterone high.
    ABP = androgen binding protein
  4. LH stimulates Leydig cells to
    secrete testosterone, which is
    essential for spermatogenesis.
  5. Testosterone acts at other body
    sites [e.g., to stimulate maturation
    of sex organs, development and
    maintenance of secondary sex
    characteristics, and libido (sex drive)].
  6. Negative feedback by testosterone
    inhibits FSH and LH release from the
    anterior pituitary and GnRH release
    from the hypothalamus.

7 Inhibin released by Sertoli cells
feeds back on the anterior pituitary,
decreasing FSH release.

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31
Q

Interstitial Leydig cells

A
  • Large, polygonal
    *Lipid droplets
    *Elaborate smooth ER
    -Testosterone synthesis from
    cholesterol
  • Differentiate to secrete testosterone in
    early fetus
    *Essential for development of male gonads
  • Period of inactivity (from about 5 months),
    activated at puberty by gonadotropins
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32
Q

Actions of testosterone on reproductive organs

A
  1. stimulates formation of male reproductive ducts, glands, external genitilia
  2. promotes descent of testes
  3. stimulates growth and maturation of internal and external genitilia at puberty
  4. promotes long bone growth
    promotes growth of larynx
  5. enhances sebum and hair growth
  6. anabolic
  7. libido in males - promotes aggressiveness
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33
Q

Functions of the oviduct/Fallopian tube

A
  • Capture of the newly ovulated oocyte
    infundibulum
  • Transport of sperm and
    oocyte(s) to the site of
    fertilisation
  • Oviductal factors facilitate
    fertilisation ampulla
  • Storage and capacitation of sperm
    isthmus
  • Supports early embryonic development
    ampulla & isthmus
  • Transport of the early embryo to the uterus
    isthmus
  • Embryo modulates the oviductal
    environment
34
Q

Sperm maturation and movement in the male reproductive tract

A
  • Maturation in epididymis
    *DNA stabilisation
    *Chromatin condensation
    *Concentration
  • Storage also in vas deferens
    before ejaculation in seminal
    fluid (= semen)
35
Q

Accessory glands

A

Seminal vesicles
* 70-75% of volume
* Alkaline fluid, fructose-rich
* Energy/muscular
contractions in female tract
Prostate
* 20-25% of volume
* Enhances sperm motility
* Proteases to fluidize the
ejaculate
* Antimicrobials
Bulbourethral glands
* Mucous secretion
(preseminal fluid)
* Lubricates end of penis
(glans penis)

36
Q

Role of the oviduct in sperm transport and maturation

A
  • Formation of a holding
    reservoir in the isthmus
  • Binds ejaculated sperm to
    the epithelium
  • Allows sperm to complete
    capacitation
  • Precisely times sperm
    transport with the arrival of
    a mature oocyte in the
    ampulla
37
Q

Capacitation: preparing the sperm for action

A

Process required before sperm can fertilise the oocyte
- Stripping of non-covalently bound epididymal/seminal
glycoproteins and sterols (e.g. cholesterol)
-  Sperm plasma membrane stability – allows release of
enzymes from acrosome
- Hyperactivation and increased motility
- Female reproductive tract ideal for capacitation
- Proteolytic enzymes,
sterol-binding albumin
- High ionic strength

38
Q

Summary of preimplantation development

A
  1. zygote
  2. 4-cell stage
  3. morula
  4. early blastocyst
  5. mature blastocyst
39
Q

Two different types of the contraceptive pill:

A
  1. The combined oral contraceptive pill (COC)
    contains estrogen and progestin
  2. The progestin only pill (POP)
40
Q

How does the pill work?

A

High plasma
estrogen
* Inhibits secretion of FSH
(and to a lesser extent, LH)
via -ve feedback (hypo & pit)
* Inhibits follicle maturation &
ovulation

High plasma
progestin
* Inhibits synthesis of LH
(via -ve feedback to the
hypothalamus & pituitary)
* Prevents LH surge
required for ovulation

41
Q

High estrogen

A

Very fluid
Enhances sperm
penetration into
uterus

Thick
Prevents sperm
penetration into
uterus

42
Q

High progesterone

A

Thickens cervical mucus
* Forms a mucus ‘plug’
around the cervix
* Prevents sperm gaining
access to the uterus

43
Q

Why choose to take the progestin only pill over
the combined pill?

A

Women who have contraindications to
taking estrogen:
* History of hypertension
* History of stroke
* History of thromboembolism (DVT)

Problems with progestin only pill
* Irregular vaginal bleeding
* Potentially higher contraceptive failure rate

44
Q

Common side effects of the COC pill

A

➢ tender breasts
➢ nausea and bloating
➢ headache
➢ weight gain/water retention
➢ less interest in sex
➢ brown patches on the face - melasma
➢ mood changes
➢ spotting

45
Q

rare side effects of the COC pill

A

➢ increased risk of rare blood clots (more likely if
>35 years and smoke)
➢ increased risk of stroke
➢ increased risk of cancer (breast, cervical)
➢ migraines
➢ dizziness
➢ increased BP

46
Q

Other hormonal contraceptive methods

A
  • Injection (e.g. Depo-Provera)
  • Vaginal ring (e.g. NuvaRing)
  • Implant (e.g. Implanon NXT)
  • Hormonal IUD (e.g. Mirena, Kyleena)
47
Q

Infertility – What are the common causes in females

A
  • Endocrine abnormalities
  • Hypothalamic dysfunction
    Weight/strenuous exercise/stress/travel
  • Pituitary disease
    Hypothyroidism/hyperprolactinemia
  • Ovarian dysfunction
  • PCOS, premature ovarian failure, abnormal follicle development
  • Implantation abnormalities
  • Luteal phase deficiency, ↓ progesterone production
  • Delayed maturation of endometrium

Reproductive:
- Disrupted cycles and ovulations
oligomenorrhea/amenorrhea
- Arrested follicle maturation
- Polycystic ovaries

Endocrine:
- Hyperandrogenism
- acne, hirsutism
- LH hypersecretion

Metabolic:
- Obesity
- Insulin resistance
- Increased risk of type 2 diabetes and cardiovascular disease

48
Q

Infertility – What are the common causes in males

A
  • 2nd most common factor (after woman’s age)
  • Varicocele – dilatation of Pampiniform plexus
  • Reduced semen quality ( temp)
  • Vas deferens blockage
  • Retrograde ejaculation – problem with ejaculation reflex
  • Hypogonadotropic hypogonadism (Kallman Syndrome)
49
Q

Other risk factors for infertility

A

Overweight or obese
Oocyte quality
Sperm quality
* Stress
Sperm production
Ovulation/cycles
* Smoking
Sperm count/quality
Oocyte quality
* Alcohol
Sperm count/quality
Impacts on ovarian reserve
Disrupted cycles

50
Q

Hormones in ART

A
  • Required for controlled ovarian hyperstimulation
  • Maximise number of follicles ovulating per cycle (1 → many)
  • Exogenous gonadotropins:
  • Injection of FSH daily for growth of follicles to large antral stage
    (monitored by ultrasound); aim for 22-35; <9 = low responder
  • Injection of LH to induce resumption of meiosis in oocyte (maturation)
    and ovulation (typically 36-40 h post-LH)
  • GnRH agonist – given continuously prior to and during
    gonadotropins to suppress natural ovulation
  • Progesterone also given for luteal support after embryo transfer
51
Q

What can go wrong with fertility treatments?

A
  • Ovarian hyper-stimulation syndrome (OHSS)
  • Due to hormone treatments for oocyte pickup
  • Women with PCOS are susceptible
  • Mild, moderate, severe, critical (can be fatal)
  • Multiple birth rate (relatively low in Australia due to SET) * Preterm delivery
  • Low birth weight babies
  • No pregnancy or miscarriage (~20% result in live birth)
  • Costly, emotionally draining, and painful for oocyte donor
52
Q

Progestin

A

synthetic form of progesterone

53
Q

COC

A

The combined oral contraceptive pill
contains estrogen and progestin

54
Q

POP

A

The progestin only pill

55
Q

ART

A

(Assisted Reproductive Technology)

Generally involve surgically removing eggs, combining them with sperm in the laboratory, and returning them to the woman’s body or donating them to another woman

Most common types of ART:
1. IVF
2. ICSI

This definition does not include:
- Treatments involving only sperm (e.g. artificial insemination, IUI)*
- Treatments to stimulate egg production/ovulation without subsequent retrieval.

56
Q

IVF

A

In Vitro Fertilisation

  • 2-3 day cleavage stage transfer or 5-6 day blastocyst transfer

General procedure:
Aim for ~8 viable embryos; transfer to mother (usually 1-2) or cryopreserve.

Issue: Often excess viable embryos

57
Q

ICSI

A

IntraCytoplasmic Sperm Injection

  • single sperm injected
  • increasingly common
  • used when male infertility measured (motility/sperm count)
58
Q

PCOS

A

Polycystic ovary syndrome
* Most common endocrine disorder of women in their reproductive years.
* Has a prevalence of 6-15% worldwide, causing major economic burden.
* Is a complex, heterogeneous disorder with reproductive, endocrine and metabolic features.
* Aetiology of PCOS is unknown and there is no cure.

59
Q

Two different types of the contraceptive pill:

A
  1. The combined oral contraceptive pill (COC) contains estrogen and progestin
  2. The progestin only pill (POP)
60
Q

Why choose to take the progestin only pill over the combined pill?

A

Women who have contraindications to
taking estrogen:
* History of hypertension
* History of stroke
* History of thromboembolism

61
Q

Problems with progestin only pill

A
  • Irregular vaginal bleeding
  • Potentially higher contraceptive failure rate
62
Q

Clinical features of PCOS

A

Reproductive:
- Disrupted cycles and ovulations - oligomenorrhea/amenorrhea
- Arrested follicle maturation - Polycystic ovaries

Endocrine:
- Hyperandrogenism - acne, hirsutism
- LH hypersecretion

Metabolic:
- Obesity
- Insulin resistance
- Increased risk of type 2 diabetes and cardiovascular disease

63
Q

Female anatomic abnormalities

A
  • Tubal disease
    Inflammatory scarring (STIs, pelvic inflammatory disease), septic abortion, surgery, IUD, salpingitis
  • Tubal blockage
  • Endometriosis
  • Uterine fibroids/polyps/septum
64
Q

Endometriosis

A
  • Abnormal growth of endometrial tissue outside the uterus in pelvic cavity
  • Responds in normal way to hormones → pain and fibrosis
  • Affects ovaries, fallopian tubes and uterus
  • Can block movement of sperm and egg/embryo in tubes
65
Q

Female fertility tests

A
  1. blood test and ultra sound
  2. X-ray
    3.ovarian reserve
66
Q

Male fertility tests

A
  1. semen analysis (sperm count, motility, morphology, consistency of seminal fluid)
  2. DNA fragmentation test
  3. Sperm aggultination
67
Q

LH

A

Luteinizing hormone (LH) is a hormone produced by the pituitary gland that plays an important role in sexual development and functioning

In women, LH is required to stimulate the ovarian follicles in the ovary to produce the female sex hormone.

In men, LH causes the testes to make testosterone.

68
Q

FSH

A

Follicle-stimulating hormone (FSH) produced by the anterior pituitary gland in response to gonadotropin-releasing hormone (GnRH) from the hypothalamus.

In males, FSH stimulates Sertoli cell proliferation, which is the most significant contributor to testicular volume in children.

In females, during the follicular phase of the menstrual cycle, FSH stimulates the maturation of ovarian follicles.

69
Q

Andorgens

A

Androgens are a group of hormones that contribute to growth and reproduction in both males and females.

Androgens are synthesized from cholesterol and are produced primarily in the gonads (testicles and ovaries) and also in the adrenal glands

In females, androgens play an important role in sexual development, libido, and bone health

70
Q

Gonadotropin

A

Gonadotropins are a group of hormones that regulate ovarian and testicular function and are essential for normal growth, sexual development, and reproduction

The human gonadotropins include 1. follicle-stimulating hormone (FSH)
2. luteinizing hormone (LH)
3. human chorionic gonadotropin (hCG)

71
Q

Granulosa cells

A

Granulosa cells are a type of cell in your ovaries that produce hormones including estrogen and progesterone.

72
Q

GnRH

A

gonadotropin-releasing hormone

controls pituitary gonadotropins

produced in the hypothalamus and released in response to circulating levels of estrogens and progesterone

73
Q

HPG

A

The hypothalamic-pituitary-gonadal (HPG)

a complex endocrine system that regulates normal growth, sexual development, and reproductive function.

74
Q

Major androgen in males

A

Testosterone

75
Q

Major androgen in females

A

DHEA

76
Q

Capacitation: preparing the sperm for action

A
  • Process required before sperm can fertilise the oocyte
  • Stripping of non-covalently bound epididymal/seminal glycoproteins and sterols (e.g. cholesterol)
  •  Sperm plasma membrane stability – allows release of enzymes from acrosome
  • Hyperactivation and increased motility
  • Female reproductive tract ideal for capacitation
  • Proteolyticenzymes, sterol-binding albumin
  • High ionic strength
77
Q

Blocks to polyspermy

A
  • Oocyte membrane block:
  • oocyte sperm-binding receptors shed
  • Cortical reaction:
  • sperm into oocyte triggers Ca2+ surge from intracellular stores in ER
  • cortical granules fuse to oocyte plasma membrane and undergo exocytosis
  • ZP hardens and destroys sperm- binding receptors (zona reaction)
78
Q

Fertilisation

A
  1. Meiotic division completed:
    - ovum and 2nd polar body formed
  2. Formation of male and female pronuclei
  3. DNA in each pronucleus
    replicates, pronuclei move
    together and mitotic spindle forms - nuclear envelopes dissolve, releasing chromosomes
  4. Maternal and paternal chromosomes combine, forming diploid zygote. = Fertilization
79
Q

Sertoli cells

A

support the developing sperm
‘nurse cells’

(also called sustentocytes) extend from basal lamina to tubule lumen and surround developing spermatogonium and all other stages

  • Maintains blood-testis-barrier
  • Provides nutrients from blood
  • Move developing sperm towards the lumen
  • Secrete testicular fluid for sperm transport
  • Phagocytosis
  • Produce androgen-binding protein
    (ABP) – concentrates T
  • Produce inhibin - -ve feedback to inhibit FSH release
80
Q

Compare oogenesis and spermatogenesis

A

Time to produce one gamete:

Oo = 13-50 years
spermo= 74 days

occurrence during lifetime
spermo= puberty to old age
oo= begins in fetal life ends menopause

number of gametes per meiotic division

spermo= 4 equal size
oo = 1 large ovum 2-3 polar bodies

number of gametes per lifetime
spermo= >1 trillion
oo = <500

error rate
spermo = 5%
oo = 20%

Cells surrounding developing gametes

spermo - one sustentocyte
oo= many granulosa cells

81
Q

Spermiogenesis = cytodifferentiation

A
  • One spermatid develops into one spermatozoan
  • Shape change: round → elongated
  • Formation of tail: motility
  • Midpiece: mitochondria for energy
  • Superfluous cytoplasm shed into tubule
  • Acrosome formation: modified lysosome structure
    ‘enzymatic knife’
82
Q

Structure of human spermatozoan

A

Head:
- Condensed nucleus
- Acrosome: contains enzymes important
for fertilisation
Midpiece:
- Metabolic region containing coiled mitochondria
- Provides energy (ATP) for motility
Tail (flagellum):
- Fibrous sheath around continuous axonemal core