Luteolysis in Cattle, Buffalo, Sheep, Dogs, Cats & Mare

Luteolysis: It is a process by which corpus luteum undergoes irreversible degeneration characterized by a dramatic
drop in blood concentration of progesterone. Harmones controlling luteolysis are Oxytocin,progesterone from CL
and PGF2α produced by uterine endometrium.

Role of uterus in luteolysis

The endocrine organ “Uterus” is responsible for producing PGF2α that causes luteolysis.
If luteolysis does not occur animal will remain in sustained luteal phase because P4 inhibits gonadotropin secretion.
During complete removal of uterus, after Ovulation CL still persists. Life-span of CL is prolonged by total
uterectomy.
In partial uterectomy, when Ipsilateral horn to CL is removed, Life-span of CL is twice as compared to normal cycle.
When contralateral uterine horn is removed,there is little or no effect on lifespan of CL. Uterus must be near to the
ovary, to normalize the life-span of CL.

Mechanism: PGF2α is transported to CL either locally, systemically or by countercurrent mechanism PGF2α from
the uterus is transported to the ipsilateral ovary through a Vascular countercurrent exchange mechanism. It
involves two closely associated blood vessels in which blood from one vessel flows in the opposite direction to that
of adjacent vessel. The PGF2α enters the uterine vein and then uterine lymph vessels as present in higher
concentration, the ovarian artery lies in close association to utero-ovarian vein.

PGF2α is transferred across the wall of uterine vein into blood of ovarian artery by passive diffusion. PGF2α thus
transported from uterus to ovary and CL without dilution.
This mechanism is important as much of PGF2α is denatured during one circulatory pass through the pulmonary
system in the ewes and the cow ( 90%). In sow, only 40% PGF2α is denatured. By entering the ovarian artery,PGF2α

can exert its lytic effect directly on CL before entering systemic circulation.
In mare, this mechanism is not successful as mare CL is more sensitive to PGF2α than cow,sow and ewe. In Mare,
Exogenous PGF2α causes luteolysis during about 60% of the cycle. In pig,CL is not responsive to single dose of
PGF2α until day 12 to 14 of the cycle.
Luteolysis occurs through series of actions including , Reduction in blood flow, downregulation of receptors
for leutotropic hormones, Inhibition of P4 synthesis.
In Mare, Exogenous PGF2α causes luteolysis during about 60% of the cycle.In pig,CL is not responsive to single dose
of PGF2α until day 12 to 14 of the cycle.

Requirements of luteolysis
 Presence of oxytocin receptors, Presence of critical level of oxytocin and PGF2α synthesis by endometrium
PGF2a Production mechanism

In addition to P4, luteal cells also secrete oxytocin,stored in nerve terminals of posterior pituitary gland,synthesized
by mRNA found in posterior pituitary gland. Luteal oxytocin pulses are nearly coincident with the pulses of PGF2α
metabolites.
During first half of luteal phase PGF2α secretion by endometrium is nonexistent. During late luteal phase, secretion
occurs in pulses which increase in frequency and amplitude at the end of luteal phase.

Luteolysis in ewes

In ewes, about five pulses in 24 hours period are required for luteolysis. Exact stimulus of PGF2α secretion is
controversial, during first half of estrus cycle, P4 prevents secretions of PGFα by blocking formation of oxytocin
receptors. After 10-12 days, P4 allows secretions of PGF2α. During late luteal phase, exogenous oxytocin injection
causes secretion of PGF2α by uterus.

In ewes, the uterine responsiveness to oxytocin is increased by rise in the number of oxytocin receptors in the
endometrium. However, the major role to secrete PGF2α is done by P4.decrease in receptors of P4 in endometrium
results in increase in PGF2α secretion.

Intracellular Mechanism

Corpus luteum caused reduction in blood supply by causing vasoconstriction of arterioles supplying the luteal
tissue. Blood flow to CL is decreased during luteolysis,but sill 5 to 20 times greater than surrounding ovarian tissue.
Capillaries in the CL undergo degeneration during luteolysis,thus causes decrease in blood flow. Other theory is that
PGF2 binds to specific receptors on large luteal cells, triggers resulting in death of cells. PGF2α in womens is
produced by corpus luteum itself.
Uterectomy has no effect on ovarian cyclicity. Oxytocin from the posterior pituitary act as ovarian oxytocin
receptors to generate small amounts of intra-ovarian PGF2α. Luteolysis is done locally and small amount of PGF2α
is required to lyse the CL.

Luteolysis in Bitch

In the bitch, immune system seems to participate in the mechanisms regulating CL-function as an increased
presence of lymphocytes within the CL could be detected at the beginning and during the latter half of dioestrus
Thus, leucocyte-derived cytokines may be important and the expression of the mRNA for interleukin tumour
necrosis factor (TNF)alpha and transforming growth factor (TGF) beta1 was observed throughout diestrus.they also
inhibit P4 secretions,
Electron microscopy confirmed the slow process of luteolysis first distinct signs of degeneration were seen on day
60, accompanied by some apoptotic events. Uterectomy has no effect on cyclicity in bitches.

Luteolysis in Bovines

In the cow, during late luteal stage,luteolysis can be induced by injection of exogenous PGF2α given at the mid
luteal stage. Although uterine PGF2α is main luteolytic factor, its direct action on the CL is mediated by the products
of accessory luteal cells: immune cells, endothelial cells, pericytes and fibroblasts.cytokines (tumor necrosis factor-
alpha, interferons) and nitric oxide play critical roles in functional and structural luteolysis in cattle by stimulating
leukotrienes and PGF2α,thus decreasing P4 secretion.
Reduced luteal blood flow and P4 concentrations decrease in parallel during both spontaneous and PGF2α induced
luteolysis.a decrease in luteal blood flow resulting in hypoxia has been proposed as one of the main luteolytic
mechanisms in the cow. Hypoxia inhibits P4 synthesis in luteal cells by inhibiting the steroidogenic enzymes and
promotes apoptosis of luteal cells.
 Luteolysis in Equines:

Exogenous PGF2α is administered to mare during diestrus which causes fluctuaution in oxytocin secretion.
In mares PGF2α and oxytocin secretion patterns are consistent with the ruminant model of the initiation of
luteolysis, in which pulsatile secretion of oxytocin from the posterior pituitary triggers episodic release of uterine
PGF2α.