Topic 8

What are the 5 steps of parturition

What causes Decidual and Myometrial Inflammation

Infiltration of leukocytes (Monocytes, granulocytes, lymphocytes) into reproductive tissues e.g. cervix, decidua, myometrium and fetal membranes prior to and during human labour

What initiates Decidual and Myometrial Inflammation

the upregulation of pro-inflammatory cytokine and chemokine secretion by the uterine tissues

What activates the myometrium

Increase in oestrogen

What does Myometrial Activation result in

Altered Progesterone Receptor Expression

• Increase in (A progesterone receptors) PR_A: PR_B ratio

• PR_A is not as responsive a progesterone B receptors 

• Reduces myometrial responsiveness to progesterone

Myometrial expression of Contraction Associated Proteins (CAPs)

What does the increased PR_A: PR_B ratio trigger

Increase expression of 20α-HSD in the myometrium

Increase expression of 20α-HSD in the myometrium leads to what

Increased irritability of myometrium (→ contraction)

Higher Progesterone Metabolism → Localised Progesterone Withdrawal

We know that Myometrial Activation leads to Myometrial expression of Contraction Associated Proteins (CAPs). Name some of these proteins

AP-1, NF KB, PGs, Connexin-43, PGF2α receptor, oxytocin receptor and COX-2

Effect of expression of Contraction Associated Proteins (CAPs)

Uterus is converted from quiescent organ to a contractile muscle

Forceful synchronous contractions to expel the mature fetus

How does Progesterone control both pro-gestation genes & pro-labour genes

Depends on the receptor it activates

What leads to the switch from PR-B (pro-gestation) dominance to PR-A (pro-labor) dominance

Increased inflammatory load

Name some sources of pro-labour signals

• Uterine distention (stretch)

• Infection

• Foetal stress

• Abruption

• Maternal stress

• Senescence (placental aging)

What tissues respond directly to pro-labour signals

Myometrium, decidua, and cervix

What 3 things do tissue-level inflammation & pro-labour signals/genes cause to happen to the cervix, decidua & myometrium

What gets released from the hypothalamus on the side of the foetus at around 40 weeks & follow that pathway down to its pro-labour effects

What is the purpose of the cortisol released by the foetus

Cortisol helps the foetus deal with the stress of labour & delivery

What is the result of the prostaglandins being released

Causes the myometrium to contract

DHEAS from the foetus makes its way to the placenta. What does it get converted to there

Estriol released from the placenta has what effect

Increases uterine contractility

What is released from the mother’s hypothalamus to contribute to the start of labour

Increased oxytocin produced & huge increase in oxytocin receptors

What effect does increased oxytocin have in initiating labour

How does the placenta contribute to lactation (what does it produce & what does that do?)

It produces oestrogen & progesterone, both of which promote growth & development of mammary glands & ducts

Also oestrogen stimulates the hypothalamus

Oestrogen stimulates the hypothalamus to do what

Inhibit the prolactin inhibitory hormone (PIH)

What produces prolactin & where does it go

Anterior pituitary gland → Mammary glands

What other endocrine glands promote the normal growth & development of mammary glands & ducts

Pancreas

Adrenal cortex

Thyroid

They don’t cause mammary growth on their own, but must be present for mammary glands and ducts to develop normally.

What hormones do these endocrine hormones produce:

Pancreas

Adrenal cortex

Thyroid

Pancreas → Insulin

Adrenal cortex → Cortisol

Thyroid → Thyroxine

The predominant pathway of lactation is stimulatory/inhibitory

Inhibitory - generally we’re not breastfeeding

True/False: At birth, prolactin begins working because it is upregulated

False - At first it works simply because inhibition is removed

It is then produced more with the sensory input of suckling

(Anterior = 1st = 1st reflex

Post = behind = 2nd reflex)

What type of drugs inhibit the milk ejection reflex

Anticholinergic drugs