Physiology of Reproduction and Endocrinology - Ovary

Celia Costa Gomes da Silva

Department of Agricultural Sciences University of the Azores
Introduction
Production of viable gametes Ovarian Production of steroid hormones
Primordial germ cells embryos ≈ 3 weeks of gestation up to multiplication by mit
osis: before birth (human, cow, sheep, goat) or a few days after birth (pig, cat
and rabbit)
Germ cell meiosis ⇒
⇒ oocyte prophase I (pachytene or diplotene)
Endocrine activity of the ovary is not necessary to develop the female phenotype
during fetal development. Top of endocrine activity ovarian ⇒ sexual transforma
tion of puberty
• Germ cells ⇒ haploid cells (female gametes) • Ageing and female gametes releas
e ⇔ ovarian endocrine activity
Oocytes released in small numbers in sporadic occasions ⇒ Ovulation
Estrogen
Major ovarian steroid excretions
Progestogens Cycle ovarian activity: estrogen ovulation → → progestogens
Cycle of ovarian activity
•
Two main phases of development
1) 2) estrus
The v u l a t i o n
Follicular development Development luteum
Estrogen-progestogen estrus
The v u l a t i o n
Luteum Development estrogen - progestins
3 6 9 12 15 Day of estrous cycle 18 21
1
Organization of the ovary - Follicles
Primordial follicle
Bovine Ovary
Follicular
Although some follicles may start their development sporadically during fetal an
d neonatal life, it is only after puberty that starts the regular recruitment of
primordial follicles to join the group of growing follicles. Thus, only a few f
ollicles begin their growth every day, forming a continuum of growing follicles.
Bovine follicles:
Follicular growth:
• Growth of the oocyte: 20-30 mm → 100-130 mm. • Increase in the synthesis of RN
A and protein synthesis. • Formation of a layer of glycoproteins that surrounds
the oocyte zona pellucida ⇒. • Growth and proliferation of granulosa cells. • Fo
rmation of a network of links gap between granulosa cells and oocyte. • Condensa
tion of ovarian stromal cells to form the theca layer. • thecal cells grow and d
ivide into two types: theca interna (highly vascularized) and theca externa (fib
rous nature). • Formation of a viscous fluid between granulosa cells comprising
mucopolissacáridos excreted by granulosa cells and other compounds from the bloo
d plasma ⇒ follicular fluid. • Differentiation of granulosa cells into cumulus o
ophorus - surround the oocyte and mural granulosa cells located near the membran
e of the follicle.
Follicular
•
Follicles grow and regress in waves during the follicular phase
Recruitment
Selection
Dominance
Regulation of follicular growth
Initiation of follicular growth: Primordial follicles ⇒ primary follicles (witho
ut return)
Ovulation atresia
Sign?
• Regardless of extra-ovarian factors • Action parócrina cytokine? EGF?
Follicular growth is continuous until such time as it becomes dependent on exter
nal support - hormonal (gonadotropins - FSH and LH). Follicular atresia:
• Reduction of protein synthesis • Accumulation of lipid droplets and pyknotic n
ucleus of the oocyte • Death • Follicle invaded by leukocytes and macrophages ⇒
fibrous tissue.
Key Reproductive Hormones
* Hypotálamo
Oxytocin-gonadotropin-releasing hormone - GnRH-Factor inhibitor of prolactin (PI
F)-FSH-LH, Prolactin
* Anterior pituitary
Gonads
Testis-Androgens (e) Ovary-Estrogens (e) Progestogens (e) Relaxin (p) Activin (p
) Inhibin (p)
p-and steroid-protein
Placenta - Estrogen (e)
Uterus
Progesterone (e) growth hormone (p) human chorionic gonadotropin (hCG) (p) - Pro
staglandins "Pregnant Mares Serum Gonadotropin (PMSG) (p)
p-protein
e-steroid
Hormone Action
Gonadotropins
LH - luteinizing hormone - FSH follicle stimulating hormone
Gonadotropins
Α subunit
Β subunit
Β subunit
LH
FSH
Molecular Weight: LH FSH-25-32.000-32-37.000 Functions: 1. Growth of ovarian fol
licles 2. Maturation of oocytes in the follicle 3. Estrogen production by follic
ular components 4. Ovulation of preovulatory follicle 5. Development of the corp
us luteum (CL) 6. Excretion by the P4 CL 7. Regulation of ovarian blood supply
Gonadotropins
Follicle stimulating hormone - FSH
1. Stimulates the development and growth of follicles 2. Stimulates estrogen pro
duction by granulosa cells in follicles romatase 3.€Stimulates the expansion of
cumulative maturation of oocytes
Luteinizing Hormone - LH
1. Stimulates the production of androgens by theca follicle cells at 2. Cause ov
ulation the release of the oocyte follicle 3. Stimulates the formation of the co
rpus luteum (luteinization of granulosa cells and theca) 4. Stimulates productio
n of progesterone by CL
GnRH - Gonadotropin-releasing hormone
10 amino acids - decapeptido MM = 1183 induces the release of LH and FSH half-li
fe time of ~ 7 minutes • GnRH causes the "surge" in LH
Pituitary GnRH LH ovulation
15
Day 18 of oestrus
21
GnRH
•
The present dominant follicle in the ovary will ovulate in response to "peak" in
duced LH
Injection of GnRH LH ovulation ovulation
1
3
6
9 12 15 Day of oestrus
18
21
Hypothalamic - Pituitary - Ovarian
ntral follicles (Graafian Follicle)
• granulosa cells to FSH receptors ⇒
• ⇒ thecal cells to LH receptors and produce hormones released by the action of
gonadotropin
Steroid hormones
Steroid hormones
Progestogens
Properties: • Preparation of the uterus Preparation
receive the embryo. Embryo • Maintenance of pregnancy. Maintaining pregnancy. •
Stimulation of the growth stimulation of mammary gland. gla mamá laughed. • Effe
ct catabolic. catabolic lico. • Regulation of the secretion of gonadotropin secr
etion regulation. gonadotropins. 20α-Hydroxyprogesterone 20α 17α 17α-Hydroxyprog
esterone (40-70%)
Estrogen
(Rel
tive potency)
Progesterone (100%)
(Rel
tive potency)
Estr
diol 17β 17β (100%)
Properties: • Stimul
tes the second
ry ch
r
cters in the second
ry
fem
le. • Prep
r
tion of the uterus for the tr
nsport of the sperm prep
r
tion.
sperm
tozo
. • Stimul
tion of
ctivity
nd growth stimul
tion of m
mm
ry gl
nd

nd endometrium. gl
m
má endometriosis trio. • Regul
tion of gon
dotrophin
 secre
tion. Regul
ting gon
dotropin secretion. • Associ
ted with the sexu
l eh
vior o
f some species. spe
Estriol (10%)
(5%)
Estrone (1%)
Androgens
Properties: • Induction
nd m
inten
nce of m
sculine differenti
tion of tissues.
M
int
ining differenti
tion induction
• Induction of m
le ch
r
cters in m
les. • Support Induction
 of sperm
togenesis.
esperm
togé nese. • Influence on sexu
l
nd
ggressive
 eh
vior in m
les
nd fe
m
les. • Promoting did influence muscle protein
n
olism, som
tic growth
nd c

lcific
tion. Promotion sum c
lcific
tion. • Regul
tion of gon
dotrophin secretio
n (testosterone). Regul
ting secretion
(Rel
tive potency)
5α-Dihydrotestosterone (100%) Testosterone (50%) Androstenedione (5%) Dehydroepi

ndrosterone (4%)

Hormon
l regul
tion

Steroid hormones: 
• Action intr
-follicul
r Androgens
 •: • • ↑ su str
te of
rom
t
se
ctivity of

rom
t
se • Estrogens: • They ind to receptors on gr
nulos
cell
rom
t
se
cti
vity • ↑ • Estrogens + FSH: • ↑ synthesis of LH receptors in gr
nulos
cells + ⇒
exterior ensures the m
inten
nce of follicul
r growth when FSH levels f
ll
Hormon
l effect on follicul
r development
(A)
Ov
ries of mice th
t were removed their pituit
ry gl
nds: (
) Untre
ted
(C)
(B) tre
ted with estrogen (c) tre
ted with FSH (d) tre
ted with estrogen + FSH
(B)
(D)
Autocrine regul
tion
nd p
rócrin


Inhi ins
nd
ctivin

Inhiins,
ctivin
nd follist
tin
Inhi in:
• ↓ secretion of FSH from the pituit
ry.• ↑ follicul
r recruitment. • ↑ product
ion of
ndrogens in thec
cells induced y LH. • ↓ tumors of the gon
ds.
Activin:
• ↑ secretion of FSH from the pituit
ry. • ↑ Expression of the FSH receptor in d
ifferenti
ted gr
nulos
cells. • ↑ Cell prolifer
tion. • ↑ Activity of
rom
t
se
. • ↑ expression of LH receptors in gr
nulos 
cells not differenti
ted. • ↓ prod
uction of
ndrogens in thec
cells induced y LH. • ↓ production of progesterone


nd luteiniz
tion of gr
nulos
cells. • ↑ m
tur
tion of oocytes. • ↑ em ryo dev
elopment.
αN:
• ↑ Ovul
tion.
proαNαC: • ↓ Action of FSH on gr
nulos
cells.
• ↓ m
tur
tion of oocytes.
Follist
tin:
• Neutr
liz
tion of the
ction of
ctivin. • In speci
l circumst
nces potenti
te
s the
ction of
ctivin. ↑ ↓ Leteiniz
ção follicul
r development
nd
tresi

Growth f
ctors
Insulin growth f
ctor - IGF Gr
nulos
+ FSH Te
k
Growth preovul
tory
After 3-12 hours of pe
k LH ⇒ m
tur
tion of the oocyte

M
tur
tion of ovine oocytes
fter the LH pe
k
Ovul
tion
Pe
k LH induces ovul
tion only in underdeveloped follicles whose gr
nulos
cells

cquire receptors for LH.
LH FSH
Luteolysis gr
nulos
cells
nd progesterone production.
+ Gr
nulos
cell pl
sminogen
ctiv
tor
 
prote
se: procol
gen
se → coll
gen
se re
kdown of the follicul
r w
ll cells te

k ⇒ renin: prote
se
Lute
l Ph
se
•
After ovul
tion formed the corpus luteum cont
ining luteinized cells (gr
nulos


nd thec
) of the follicle th
t ovul
ted.
Lute
l Ph
se estrus estrus
1
3
6

Septem er 12th D
y of oestrus
15
18
21
Corpus luteum (CL) 
Luteinized gr
nulos
cells progesterone + te
k ⇒ Yellow ody
(Estrogen) Prim
te
Dur
tion of the corpus luteum in nonpregn
nt ⇒ 2 - 14 d
ys
Regression
 of the corpus luteum (luteolysis) ⇒ ↓ ⇒ progesterone production corpu
s
l ic
ns

Yellow ody
Uterus
Oxytocin
↑ Prost
gl
ndin F2α
Luteolysis
Other th
n prim
tes
Oestrus or menstru
l cycle (prim
tes) 
Functions:
 • Unlocking the g
metes (oocytes) to e fertilized. • Prep
re the sit
e of em ryo impl
nt
tion if fertiliz
tion h
s occurred.
Wom
n
Cow
Oestrus Ve
l
•
Follicul
r w
ves
- With
dur
tion of 7-12 d
ys - usu
lly two or three w
ves during
n estrous cy
cle
estrus
Follicul
r 1st W
ve 2nd W
ve Follicul
r
estrus
3rd W
ve Follicul
r
P
4
1
3
6
9 12 15 D
y of oestrus
18
21
Follicul
r w
ves
Selection of domin
nt follicle
Selection process of the domin
nt follicle
(Mono-ovul
tory species)
Assumptions:
• Selection of the domin
nt follicle: ↓ ↓ FSH FSH follicle growth
+ ⇒ follicle developed expression of LH receptors in gr
nulos
cells of domin
nt
follicle growth LH
• domin
nt follicle

f
ctor inhi iting the growth of rem
ining follicles.
⇒ loc
l effect demonstr
ted in vitro studies. Not expl
in the effect in the othe
r ov
ry.
How m
ny follicles ovul
te in
cycle?
Oocyte m
tur
tion
nd fertiliz
tion
Imm
ture oocytes (proph
se I)
After oocyte m
tur
tion (met
ph
se II)
Oocyte
fter fertiliz
tion

Em ryonic Development

Inhi ins,
ctivin
nd follist
tin in the oocyte
Imm
ture

)

After M
tur
tion

)
After Fertiliz
tion
c)
α
m)
n)
o)
Pro-α
Imm
ture
d)
After M
tur
tion
e)
After Fertiliz
tion
f)
βA
g)
h)
i)
βB
j)
k)
l)
FS