Meiosis, Mitosis, Uterus and Uterine Cycle

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Spermatogenesis,

Oogenesis, Uterus &


Uterine Cycle
Ms Moratuwa January
Anatomical Sciences
[email protected]
Disclaimer
Please note that the purpose of this lecture is to
provide an overview of the work. Lecture notes
alone are not sufficient to prepare for tests and
examinations. Students are advised to
supplement with readings from the prescribed
textbook, completion of exercises from the
practical manual and other relevant resources.
• Knowledge of spermatogenesis and oogenesis.

• Understand the process of meiosis and mitosis.

• Histological structure and function of the ovary and uterus

• Hormonal influence and cyclical changes in structure and


function within ovary and uterus

• Implantation, implantation window and decidualisation


• Basic overview of mitosis and meiosis.
• Basic understanding of spermatogenesis and oogenesis.
• Provide the general histology of the ovary
• Provide the detailed histology of the ovarian follicles, including their location and
• function: primordial follicle, primary unilaminar follicle, primary multilaminar
follicle, secondary antral follicle and tertiary (mature), Graafian follicle
• Comment on the influence of the hypothalamus and pituitary on the
hormonal secretion within the ovary
• Provide the histology of the Corpus luteum and its corresponding endocrine
function
• Provide the general histology of the uterus
• Provide the histological structure of the endometrium during the proliferative,
secretory and menstrual phases
• Explain the influence of the hypothalamus-pituitary-ovarian axis on the events
taking place during the three phases of the menstrual cycle
• Relate the events that simultaneously take place in the ovary and uterus during
the 28 day menstrual cycle
• Overview of decidualisation and the window of receptivity.
Mitosis & Meiosis
What is mitosis?
Mitosis is a type of cell division in which one cell (the mother) divides to
produce two new cells (the daughters) that are genetically identical to itself.
In the, the cell cycle, mitosis is the part of the division process.
DNA of the cell's nucleus is split into two equal sets of chromosomes.

During development and growth, mitosis populates an organism’s body


with cells, and throughout an organism’s life, it replaces old, worn-out cells
with new ones.

The “goal” is to make sure that each daughter cell gets a perfect, full set of
chromosomes.

Cells with too few or too many chromosomes usually don’t function well:
they may not survive, or they may even cause cancer. Cells don’t just
divide their DNA at random and toss it into piles for the two daughter
cells.

Instead, they split up their duplicated chromosomes in a carefully


organized series of steps.
What is Meiosis?
Meiosis is a process where a single cell divides twice to produce four cells
containing half the original amount of genetic information. These cells are
our sex cells – sperm in males, eggs in females.

•During meiosis one cell? divides twice to form four daughter cells.

•These four daughter cells only have half the number of chromosomes? of
the parent cell – they are haploid.

•Meiosis produces our sex cells or gametes? (eggs in females and sperm in
males).

•Meiosis can be divided into nine stages. These are divided between the first
time the cell divides (meiosis I) and the second time it divides (meiosis II):
Meiosis
Meiosis Continued
Spermatogenesis
Spermatogenesis
• Phases:
– Spermatogonial phase –
spermatogonia divide by
mitosis
– Spermatocyte phase –
primary spermatocytes
undergo meiotic divisions
to produce haploid
spermatids
– Spermatid phase
(spermiogenesis) –
spermatids differentiate
into mature spermatozoa
• Mature sperm
– Head: flattened
contains
acrosomal
enzymes
– Tail: subdivided
into the neck,
middle piece,
principal piece,
end piece
SEMINIFEROUS TUBULE

Myoid Cell
Sertoli
Cells
Primary
Spermatocyte
Spermato-
" ♦ ......\-- -=- ;....._..=; - - - 1 1 - - -
gonium
Spermato
gonium
Lumen

Early
Spermatids
Late
Spematids

Spermato
+- - - - ;;; --=---- - 1-- goniu
m
oogenesis
http://monashivf.com/wp-content/uploads/2012/09/female-anatomy2.jpg
http://www.buzzle.com/articles/ovaries-function.html
1. Production of gametes – gametogenesis

• Female - Oogenesis
• Developing gametes - oocytes
• Mature gametes - ova
• Oogonia (fetal life)  oocytes (at birth, arrested at the first meiotic
division)  ova (puberty)

2. Production of hormones – steroidogenesis

Oestrogen - growth and maturation of internal and external sex


organs and development of female sex characteristics (puberty) +
mammary gland development
Progesterone - secretory changes in the endometrium + mammary
gland proliferation (lactation)
Lining cuboidal ‘germinal’
epithelium (instead of mesothelium)

Tunica albuginea
(dense connective tissue)

Medulla - loose CT Cortex - cellular CT + SM


1. Primordial follicles

Unilaminar
Primary
Multilaminar
2. Growing follicles

Secondary - Antral

3. Mature or Graafian follicles


Ovarian follicles provide the
microenvironment for the
developing oocytes
3rd month of fetal
• Primordial germ cells development;
Extragonadal origin (migrate from embryonic yolk  Oocyte at birth
cortex of embryonic gonad) arrested in
development

• Primordial follicles
First appear during 3rd month of fetal
development (no gonadotropin stimulation)
Oocyte at birth arrested in development at the
first meiotic division (600,000-800,000)
Puberty - follicles undergo cyclic changes and
maturation

• Growing follicles (microenvironment for


developing oocyte)
• Primary follicles (unilaminar 
multilaminar)
• Secondary (antral) follicles

• Mature (Graafian) follicles


400 during reproductive life

http://dev.biologists.org/content/142/15/2554
• Oocyte - Ooplasm with large eccentric
nucleus, dispersed chromatin and 1-2
nucleoli
• Follicular cells - single layer of squamous
follicle cells + Basal lamina (outer surface)

http://www.cytochemistry.net/microanatomy/medical_lectures/female_reproduc
tive_system_ovary.htm

http://en.wikipedia.org/wiki/Histology http://www.meddean.luc.edu/LUMEN/MedEd/Histo/frames/histo_frames.html
http://www.udel.edu/biology/Wags/histopage/histopage.htm
• Centrally placed oocyte
• Surrounded by the gel like zona pellucida
(ZP) (glycosaminoglycans and glycoproteins)
• Follicle cells = granulosa cells (GC) proliferate
– single layer of cuboidal cells
• Stromal cells form theca folliculi

http://www.cytochemistry.net/microanatomy/medical_lectures/female_reproductive_
system_ovary.htm

http://en.wikipedia.org/wiki/Histology http://www.meddean.luc.edu/LUMEN/MedEd/Histo/frames/histo_frames.html
http://www.udel.edu/biology/Wags/histopage/histopage.htm
• Oocyte enlarging
• Granulosa layer – stratified layer of follicle cells
• Theca interna - steroid producing cuboidal cells, LH
influence (LH receptors) - androgen > oestrogen
(granulosa cells) + fibroblasts, collagen fibers and
rich blood supply
• Theca externa - smooth muscle and collagen fibers
• Boundaries between thecas and maturation of the
oocyte

http://en.wikipedia.org/wiki/Histology http://www.meddean.luc.edu/LUMEN/MedEd/Histo/frames/histo_frames.html
http://quizlet.com/12908246/bio-142-female-reproductive-flash-cards/
• Factors for follicular maturation - FSH,
growth factors and Ca2+
• Stratum granulosum or granulosa cells
(GC) 6-12 layers
• Fluid (liquor folliculi) forms cavities
• Antrum - single crescent shape
• Oocyte eccentrically displaced (no further
growth)

http://en.wikipedia.org/wiki/Histology http://www.meddean.luc.edu/LUMEN/MedEd/Histo/frames/histo_frames.html

https://www.studyblue.com/notes/note/n/secondary-follicle/deck/11689619
• Spaces between GC enlarge while the
GC layer increases in size
• GC no longer produce oestrogen in
response to LH
• Meiosis complete, secondary oocyte
and first polar body formed
• Cumulus oophorus
• Oocyte ready to be released
surrounded by corona radiata
• Theca interna – steroid producing
cells (FSH  Oestrogen)
• Ovulation

http://en.wikipedia.org/wiki/Histology http://www.meddean.luc.edu/LUMEN/MedEd/Histo/frames/histo_frames.html
http://www.udel.edu/biology/Wags/histopage/histopage.htm
• Female reproductive organs undergo regular structural and
functional cyclic changes from puberty to menopause

• Changes related to neural activity and changes in hormone levels


during each menstrual cycle and pregnancy

• Menarche – occurs in females between 9-14 years - End of puberty


and beginning of the reproductive life

• Menstrual cycle

• Menopause (climacterium) – “change of life”


Follicular phase Luteal phase

Ovarian
cycle

Pituitary
hormones

Ovarian
hormones

Uterine
cycle

Proliferative phase Secretory phase

http://monashivf.com/wp-content/uploads/2012/09/female-anatomy2.jpg
http://en.wikipedia.org/wiki/Histology http://www.meddean.luc.edu/LUMEN/MedEd/Histo/frames/histo_frames.html
http://www.udel.edu/biology/Wags/histopage/histopage.htm
https://yildontanju.tr.gg/Korpus-Hemorajikum-Kist-R.ue.pt.ue.r.ue..htm
Hormone mediated process
resulting in the release of the
secondary oocyte (viable for
24h)

http://en.wikipedia.org/wiki/File:Blausen_0404_Fertilization.png
The actual release of the secondary oocyte influenced by:

• Increase in volume and pressure of the follicular fluid


• Enzymatic proteolysis of the follicular wall by activated plasminogen
• Hormonally directed deposition of glycosaminoglycans between the oocyte
–cumulus complex and the stratum granulosum
• Contraction of the smooth muscle fibers in the theca externa triggered by
prostaglandins
The collapsed follicle after
ovulation
Stroma
• Corpus haemorrhagicum
• Temporary structure with a central clot
SG
• CT from stroma invades the lumen

• LH influence – Corpus Haemorragicum


Blood becomes Corpus luteum
clot

http://kobiljak.msu.edu/cai/histology/Hist14_06.htm
• Granulosa lutein cells and Theca lutein
cells increase in size and filled with lipid

• Lipochrome – yellow appearance

• Highly vascularized structure

• Luteal phase - Secretion of P and E 


preparation for implantation

• Corpus luteum of menstruation - If


implantation does not occur (active for
14 days)

• Corpus luteum of pregnancy - If


implantation occurs - active for 6 weeks
until placenta takes over

http://embryology.med.unsw.edu.au/embryology/index.php?title=File:Corpus_luteum_lutein_cells.jpg
• Corpus albicans forms in the absence of
fertilization (absence of hCG)

• Decreased P and E – degeneration of


corpus luteum (10-12 days after ovulation)

• Cells loaded with lipids and fibrous tissue,


decrease in size, degenerate and undergo
autolysis

• Later phagocytosed by macrophages

• Intercellular hyaline material (white scar)

http://www.vetmed.vt.edu/education/curriculum/vm8054/Labs/Lab28/lab28.htm
http://biology-forums.com/index.php?action=gallery;sa=view;id=8250
http://www.histology-world.com/photoalbum/displayimage.php?album=39&pid=3619
Lumen

Perimetrium

http://www.onlineveterinaryanatomy.net/content/canine-uterine-tissue-histology
http://courses.md.huji.ac.il/histology/female/XIII-6a.html
The uterine wall has three layers:
• Endometrium (E)
• Myometrium (M)
• Perimetrium (P)
Primarily endometrium (& myometrium) undergo cyclic changes
(menstrual cycle)
Stratum functionale (SF)

Stratum basale (SB)

Myometrium (M)
• Uterine artery  6-10 arcuate arteries
(myometrium)

• Branches = radial arteries (str. basale)

• Branches = straight arteries; main


branch = spiral artery (Str. functionale)

• Arterioles, capillaries, lacunae

• Only distal portion of spiral arteries


change under the influence of P and E2
Three phases of the menstrual cycle:

• Proliferative – influenced by Oestrogen (E2)


Coincides with follicular maturation (follicular phase or pre-ovulatory phase of
the ovary)

• Secretory – influenced by Progesterone (P)


Coincides with corpus luteum (CL) function - (luteal or post-ovulatory phase
of the ovary)

• Menstrual
( P and E2) coincides with CL degeneration
E

M
• Epithelial cells reconstitute the glands and migrate to cover
endometrial surface
• Stromal cells proliferate
• Spiral arteries lengthen (bottom 2/3 of endometrium)
• Glands with narrow lumina and relatively straight

St. Rosemary Education Institution © 2010-2015


SF

SB
• Endometrium becomes edematous
• Glands enlarge and become corkscrew
• Lumina filled with secretory products (glycogen)
• Spiral arteries lengthen and coil (almost to the surface of the
endometrium)
• Stromal cells decidualise (favorable environment)

http://www.proteinatlas.org/learn/dictionary/normal/uterus/detail+1
SF

SB

http://www.bu.edu/histology/p/19202ooa.htm
• Hormone levels decline (CL - CM)
• Periodic contraction of the spiral artery walls
• Stratum functionale becomes ischemic
• Glands stop secretion
• Endometrium shrinks, stroma less edematous
• Disruption of the surface epithelium
• Vessels rupture

medcell.med.yale.edu
https://quizlet.com/22133175/srwk1-tuesday-flash-cards/
Decidualisation
Decidualisation

Decidualization is a process that results in significant changes


to cells of the endometrium in preparation for, and
during, pregnancy.

This includes morphological and functional changes


(the decidual reaction) to endometrial stromal cells (ESCs), the
presence of decidual white blood cells (leukocytes), and
vascular changes to maternal arteries.

The sum of these changes results in the endometrium


changing into a structure called the decidua. In humans, the
decidua is shed during childbirth.
Decidualisation

Decidualization plays an important role in promoting placenta


formation between a mother and her fetus by mediating the invasiveness
of trophoblast cells.

It also triggers the production of cellular and molecular factors that result in
structural changes, or remodeling, of maternal spiral arteries.

Decidualization is required in some mammalian species where


embryo implantation and trophoblast cell invasion of the endometrium
occurs, also known as hemochorial placentation.

This allows maternal blood to come into direct contact with the
fetal chorion, a membrane between the fetal and maternal tissues, and
allows for nutrient and gas exchange.
Decidualisation

In humans, decidualization occurs after ovulation during the menstrual


cycle. After implantation of the embryo, the decidua further develops to
mediate the process of placentation.

In the event no embryo is implanted, the decidualized endometrial lining


is shed or, as is the case with species that follow the oestrogen cycle
absorbed. In menstruating species, decidualization is spontaneous and
occurs as a result of maternal hormones.

In non-menstruating species, decidualization is non-spontaneous,


meaning it only happens after there are external signals from an
implanted embryo.
Decidualisation
Window of receptivity
Window of receptivity
The implantation window is defined as that period when the uterus is
receptive for implantation of the free-lying blastocyst.

This period of receptivity is short and results from the programmed


sequence of the action of oestrogen and progesterone on the
endometrium.

Implantation itself is a process that commences with apposition, continues


through attachment to trophoblast outgrowth and decidualization.

For maximal effectiveness of assisted reproductive technologies in women,


it is important to know the optimal time for embryo transfer which implies
a need to predict the period of uterine receptivity.

At present there are no good markers of, or for prediction of, uterine
receptivity.
Window of receptivity

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