Physio Final

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Spermatogenesis refers to

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the entire sequence of events by which primitive germ cells (spermatogonia) are transformed into sperms or spermatozoa.
This maturation process of germ cells begins at puberty (13 years) and continues into old age

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Spermatogonia

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which have been dormant in the seminiferous tubules of the testes since the fetal period, begin to increase in number at puberty .After several mitotic divisions, the spermatogonia grow and transform into primary spermatocytes.

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Each Primary spermatocyte subsequently undergoes a

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reduction division (the first meiotic division) to form two haploid secondary spermatocytes

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Secondary spermatocytes undergo a

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second meiotic division to form four haploid spermatids

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spermiogenesis

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Spermatids are gradually transformed into four mature sperms by a differentiation process

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Sperms are transported to the

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epididymis, ductus deferens, and urethra

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Sertoli cells:

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lining the seminiferous tubules support and nurture the germ cells, and may be involved in the regulation of spermatogenesis.

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Head of the sperm (contains

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nucleus)

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Acrosome

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(enzymes, acrosin)

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Tail of the sperm: middle piece

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(mitochodria, ATP), principal piece, end piece.

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Picture ppt 16

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slide 3

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The hypothalamus is the
regulates

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integrative center of the reproductive axis and receives messages from both the central nervous system and the testes to regulate the production and secretion of gonadotropin releasing hormone (GnRH).

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Neurotransmitters and neuropeptides have both

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inhibitory and stimulatory influence on the hypothalamus.

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The hypothalamus releases

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GnRH in a pulsatile nature which appears to be essential for stimulating the production and release of both luteinizing hormone (LH) and follicle stimulating hormone (FSH).

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after the initial stimulation of these gonadotropins, the exposure to constant GnRH results in

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inhibition of their release.

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LH and FSH are produced in the

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anterior pituitary

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LH and FSH

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are secreted episodically in response to the pulsatile release of GnRH.

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LH and FSH both bind to specific receptors on the

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Leydig cells and Sertoli cells within the testis

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Testosterone, the major secretory product of the testes, is a primary inhibitor of

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LH secretion in males.

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Testosterone may be metabolized in

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peripheral tissue to the potent androgen dihydrotestosterone or the potent estrogen estradiol.

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androgens and estrogens act

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independently to modulate LH secretion

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The mechanism of feedback control of FSH is regulated by

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a Sertoli cell product called inhibin.

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Decreases in spermatogenesis are accompanied by

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decreased production of inhibin and this reduction in negative feedback is associated with reciprocal elevation of FSH levels.

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Isolated increased levels of FSH constitute an important,

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sensitive marker of the state of the germinal epithelium.

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Male fertility
Depends on the

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number and motility of sperm

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The average volume of semen in a normal, fertile male ejaculate is

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3.5 ml, with a concentration of about 100 million sperm/ml of semen.
10% usually is deformed

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Erection is achieved by

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parasympathetic nerve-induced vasodilation of arterioles that allows blood to flow into the corpora cavernosa of the penis.

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The neurotransmitter that mediates this increased blood flow in an erection is

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nitric oxide. Nitric oxide, released in the penis in response to parasympathetic nerve stimulation, diffuses into the smooth muscle cells of blood vesseles and stimulates the production of cGMP. The cGMP, in turn, causes the vascular smooth muscle to relax, so that blood can flow into the corpora cavernosa.

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Emission is controlled by

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sympathetic

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Ejuaculation is controlled by

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sympathetic and parasympathetic.

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Leydig cells secrete

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Testosterone episodically in response to LH pulses which has a diurnal pattern, with the peak level in the early morning and the trough level in the late afternoon or early evening. In the intact testis, LH receptors decrease or down-regulate after exogenous LH administration

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The seminiferous tubules contain

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all the germ cells at various stages of maturation and their supporting Sertoli cells. These account for 85-90% of the testicular volume. Sertoli cells are a fixed-population of non-dividing support cells.

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Oogenesis

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Refers to the transformation of oogonia into mature oocytes

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Prenatal maturation of oocytes:
During early fetal life, oogonia proliferate

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by mitotic division. Oogonia enlarge to form primary oocytes before birth

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connective tissue cells surround this single layer

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follicular epithelial cells

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As the primary oocyte enlarges during puberty, the follicular epithelial cells become cuboidal in shape and then forming a

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primary follicle

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Primary oocyte becomes surrounded by a covering of

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amorphous acellular glycoprotein material called the zona pellucida.

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When the primary follicle has more than one layer of cuboidal follicular cells, it is called a

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maturing or secondary follicle

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Primary oocyte begin the first meiotic division before

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birth, and remain in suspended until sexual maturity and the reproductive cycles begin during puberty

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The follicular cells surrounding the primary oocyte secrete

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oocyte maturation inhibitor (OMI), which keeps the meiotic process of the oocyte arrested

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Postnatal maturation of oocytes Begins during

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puberty, usually one follicle matures each month and ovulation occurs.
No primary oocytes form after birth in females, the primary remain dormant in the ovarian follicles until puberty.

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As a follicle matures, the primary oocyte

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increases in size and shortly before ovulation, completes the first meiotic division

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At ovulation the nucleus of the secondary oocyte begins

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the second meiotic division.

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If a sperm penetrates the secondary oocyte,

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the second meiotic division is completed, (the fertilized oocyte, or mature ovum.)

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The uterus averages length and width

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7-8 cm length. 5-7 cm width

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Klinefelter syndrome

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XXY

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Ovulation is triggered by a surge of

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LH production. Ovulation usually follows the LH peak by 12-24 hour
A small avascular spot, the stigma, soon appears on this swelling, then the stigma ruptures, expelling the secondary oocyte with the follicular fluid.

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Corpus luteum
It secrets

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progesterone and estrogen

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If the oocyte is fertilized, the corpus luteum enlarges to form a

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corpus luteum of pregnancy and increases its hormone production. (under control human chorionic gonadotropin, hCG).

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If the oocyte is not fertilized corpus luteum begins to

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degenerate about 10 to 12 days
after ovulation. It is transformed into white scar tissue in the ovary called a corpus albicans.

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If fertilization does not occur, the corpus luteum

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degenerates and is replaced by connective tissue forming a corpus albicans.

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Fertilization normally takes place within the

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uterine tubes (ampulla), after ovulation has occurred

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During the menstrual mid cycle, the cervical mucus changes to become

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more abundant, thinner and more watery. These changes serve to facilitate entry of the sperm into the uterus and to protect the sperm from the highly acidic vaginal secretions.

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Passage of sperm through corona radiata surrounding the zona pellucida of an oocyte.
Penetration of zona pellucida surrounding the oocyte. (enzymes: neuraminidase, acrosin)
Fusion of plasma membranes of the oocyte and sperm
Completion of second meiotic division of oocyte and formation of female pronucleus

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Formation of male pronucleus
Membranes of pronuclei break down, the chromosomes condense and become arranged for a mitotic cell division.
The fertilized oocyte or zygote is a unicellular embryo. The combination of 23 chromosomes in each pronucleus results in a zygote with 46 chromosomes

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LH peaks

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before ovulation

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oestrogen peaks

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during ovulation

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temp rises

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during ovulation

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Traditionally a human pregnancy is considered to last approximately

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40 weeks (280 days) from the LMP, or 38 weeks (266 days) from the date of fertilization.

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Presence of in the blood and urine, detectable by laboratory testing; this is the most reliable early sign of pregnancy
-Missed menstrual period.

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human chorionic gonadotropin (hCG

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the post-implantation phase, the blastocyst

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secretes a hormone named human chorionic gonadotropin which in turn, stimulates the corpus luteum in the woman's ovary to continue producing progesterone. This acts to maintain the lining of the uterus so that the embryo will continue to be nourished

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Uterine contractions are known to be stimulated by two agents:

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Oxytocin
prostaglandins (PGF2alpha, PGE2)

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A hormone have a permissive effect on the action of a second hormone when it

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enhances the responsiveness of a target organ to the second hormone or when it increases the activity of the second hormone.
Example: Cortisol and catecholamines

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Some hormones bind cell surface receptors,

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e.g., insulin, growth hormone, prolactin

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Some hormones bind to intracellular receptors that act in the nucleus,

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e.g., steroids, thyroid hormone.

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G-proteins are

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guanosine triphosphate (GTP)-binding proteins that couple
receptors to adjacent effector molecules

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G-protein coupled receptors used in the adenylate cyclase,

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Ca2+_ Calmodulin, and inositol 1,4,5-triphosphate
(IP3) second messenger system.

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Binding of ligand to the receptor activates G proteins, which in turn act on

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effectors
such as adenylyl cyclase and phospholipase C and in that way initiate production of
second messengers with resultant influences on cell organization, or transcription.

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The α subunit can bind .

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GDP or GTP. When GDP is bound to α subunit, the G protein
is inactive. When GTP is bound, the G protein is active

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G proteins are either stimulatory (Gs) or inhibitory (Gi). Stimulatory or inhibitory activity
resides in the

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α subunits, which are accordingly called (αs) and (αi)

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Cytokine receptors: are part of a receptors that also mediate the actions of
growth hormone (GH). This class contains a surface-exposed amino terminal
domain that binds ligand, a single membrane-spanning domain, and a carboxyl
terminal effector domain.

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GH receptors lack a tyrosine kinase domain, when GH bind to the receptor in the extracellular space (their mechanism of action is not perfectly understood ) but appears to involve the participation of signaling intermediates, like JAK2, a protein that possesses intrinsic tyrosine kinase activity. The association of JAK2 with the liganded GH receptor leads to change in JAK2 and activation of its tyrosine kinase catalytic activity. This, in turn, triggers downstream signaling events.

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Growth factor receptors

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contains an amino terminal surface exposed ligand-binding domain, a single
membrane-spanning domain, and a carboxyl terminal catalytic domain.

Growth factor receptors, including those for insulin, IGF and EGF, possess tyrosine kinase activity. Ligand binding results to activation of tyrosine kinase, and
autophosphorylation.

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Ligand-regulated transporters (Guanylyl cyclase receptor)

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can bind ligands and respond by opening the channel for ion flow.
In this case, the ion flux acts the second messenger, it increases nitric oxide synthases (NOS) , it leads to stimulation of soluble guanylyl cyclase (GC) activity. Subsequent elevations in cGMP activate cGMP -dependent protein kinase (PKG) and promote vasorelaxation.

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Nuclear receptors

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Nuclear receptors mediate actions of steroid hormones, vitamin D, thyroid hormones,
retinoids, fatty acids and bile acids.
Nuclear receptors control gene expression by binding to DNA response elements
in the promoters of target genes or to other transcription factors.

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Nuclear receptor is composed of three domains:

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The amino terminal domain is the most variable and mediates
effects on transcription.
2- The DNA-binding domain
3-The carboxyl terminal domain
is also well conserved and mediates ligand
binding, dimerization, and effect on transcription.

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Steroid hormone and thyroid hormone mechanism

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Steroid or thyroid hormones diffuse across
the cell membrane of target cells and bind to
a cytosolic receptor and then to a nuclear receptor.
Binding to the nuclear receptor causes a
conformational change in the receptor,
which exposes a DNA-binding domain.

2- In the nucleus, the DNA-binding domain on
the receptor interacts with the hormone
regulatory elements of specific DNA.
Transcription is initiated and results in the
production of new mRNA.

3- mRNA is translated in the cytoplasm and
results in the production of specific proteins
that have physiologic actions.

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PPT 2 and

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3

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Growth factor receptors

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contains an amino terminal surface exposed ligand-binding domain, a single
membrane-spanning domain, and a carboxyl terminal catalytic domain.

Growth factor receptors, including those for insulin, IGF and EGF, possess tyrosine kinase activity. Ligand binding results to activation of tyrosine kinase, and
autophosphorylation.

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Ligand-regulated transporters (Guanylyl cyclase receptor)

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can bind ligands and respond by opening the channel for ion flow.
In this case, the ion flux acts the second messenger, it increases nitric oxide synthases (NOS) , it leads to stimulation of soluble guanylyl cyclase (GC) activity. Subsequent elevations in cGMP activate cGMP -dependent protein kinase (PKG) and promote vasorelaxation.

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Nuclear receptors

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Nuclear receptors mediate actions of steroid hormones, vitamin D, thyroid hormones,
retinoids, fatty acids and bile acids.
Nuclear receptors control gene expression by binding to DNA response elements
in the promoters of target genes or to other transcription factors.

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Nuclear receptor is composed of three domains:

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The amino terminal domain is the most variable and mediates
effects on transcription.
2- The DNA-binding domain
3-The carboxyl terminal domain
is also well conserved and mediates ligand
binding, dimerization, and effect on transcription.

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Steroid hormone and thyroid hormone mechanism

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Steroid or thyroid hormones diffuse across
the cell membrane of target cells and bind to
a cytosolic receptor and then to a nuclear receptor.
Binding to the nuclear receptor causes a
conformational change in the receptor,
which exposes a DNA-binding domain.

2- In the nucleus, the DNA-binding domain on
the receptor interacts with the hormone
regulatory elements of specific DNA.
Transcription is initiated and results in the
production of new mRNA.

3- mRNA is translated in the cytoplasm and
results in the production of specific proteins
that have physiologic actions.

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PPT 2 and

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3