Parturition and lactation

Faculty of Medicine

  • The Chinese University of Hong Kong (CUHK)

  • School of Biomedical Sciences

Learning Outcomes

Parturition

  • Describe hormonal and mechanical mechanisms in timing and initiation of labor.

  • Explain endocrine control by maternal and fetal uterotrophins.

  • Describe changes in the cervix during parturition and list key regulators.

  • Explain uterotonics and tocolytics.

Lactation

  • Describe mammogenesis and lactogenesis processes and their hormonal control.

  • Explain the development of lactational amenorrhea and its use in family planning.

Uterine Activity During Parturition

Inhibitors

  • Progesterone: inhibits myometrial contraction.

  • Relaxin: contributes to myometrial quiescence.

Uterotrophins

  • Estrogen: promotes uterine preparatory phases.

  • Cortisol: impacts labor onset.

  • Cytokines: modulate uterine responses.

Mechanical Agents

  • Mechanical Stretch: stimulates contractility, especially in multiple pregnancies.

  • Gap Junctions and Oxytocin Receptors: crucial for contractile activity.

Uterotonins (Stimulators)

  • Oxytocin: promotes contractions.

  • Prostaglandins: enhance uterine contractility.

Phases of Uterine Contractile Activity

  • Phase 0 (Quiescence): Myometrial quiescence maintained by progesterone and relaxin.

  • Phase 1 (Preparation for Labor): Induced by uterotrophins; begins expressions of contraction-associated proteins (CAPs).

  • Phase 2 (Active Labor): Uterotonins stimulate active contractions expelling fetus and placenta.

  • Phase 3 (Involution): Post-delivery recovery of uterus to its pre-pregnancy size (~6 weeks).

Proposed Mechanisms for Onset of Human Parturition

  • Hormonal Mechanisms:

    • Placental production of CRH (Chorionic Gonadotropin).

    • Maturation of fetal pituitary-adrenal axis.

    • Functional withdrawal of progesterone and estrogen activation.

  • Mechanical Mechanisms:

    • Stretching of uterus, including artificial/spontaneous rupture of membranes.

  • Result in increased prostaglandin production and sensitivity to oxytocin.

Endocrine Control of Human Parturition

CRH and Hormonal Rise

  • CRH bioavailability increases from decrease in CRH-binding protein at pregnancy's end.

  • Stimulates fetal ACTH secretion and adrenal production of DHEA/DHEAS and cortisol.

Fetal Adrenal Axis Development

  • Maturation leads to increased cortisol leading to positive feedback enhancing CRH production and aiding fetal organ development.

Hormonal Effects

  • Cortisol promotes a positive loop with placental CRH and aids in fetal organ systems (e.g., lung maturation).

  • Maternal cortisol exert moderated effects due to placental enzymes inactivating cortisol.

Progesterone and Estrogen Balance

  • High progesterone levels remain but ratio of estrogen increases, leading to activation of CAPs.

    • Estrogen production increases by:

    • Enhanced placental production.

    • Altered receptor expression ratios between PR-A and PR-B.

    • Metabolism of progesterone to inactive forms (inducing unliganded PR-A).

    • Increased expression of estrogen receptors (ERα).

Contraction-Associated Proteins (CAPs)

  • Promote myocyte contractility:

    • Facilitate prostaglandin production for cervical ripening.

    • Promote oxytocin/prostaglandin receptor sensitivity.

    • Increase myocyte excitability via Ca2+ channel modulation.

    • Enhance intercellular connectivity through gap junctions for synchronized contractions.

Mechanical Control of Human Parturition

  • Stretching uterine musculature enhances contractility via stretch sensors.

  • Stretch or irritation of cervix initiates contractions via nervous reflexes or myogenic signals.

Active Labor

  • Maintained by oxytocin and prostaglandins in a positive feedback loop (Ferguson reflex) from cervix mechanoreceptors.

  • Oxytocin facilitates fetal expulsion and placenta delivery by enhancing uterine contractions.

Cervical Ripening

  • Towards labor onset, the cervix softens and changes shape through effacement (thinning) and dilation (opening).

  • The Bishop score assesses the readiness of the cervix for labor, detailed by:

    • Signs: Bloody show, mucus passage, pelvic pain.

    • Effacement: Ranges 0% (no thinning) to 100% (fully thinned).

    • Dilation: Ranges from 0 cm (closed) to 10 cm (fully opened).

Control of Cervical Remodeling

  • Cervical ripening involves gene regulation for inflammation-like processes, with leukocyte infiltration and collagen degradation.

  • Stimulation factors include: Estrogen, CRH, PGE2, IL-8, Relaxin, NO; and inhibited by Progesterone.

Summary on Control of Labor/Parturition

  • Parturition onset is triggered via hormonal and mechanical stimuli leading to increased prostaglandin production and sensitivity to uterotonins.

  • In active labor, oxytocin maintains a positive feedback for uterine contractions.

Phase 3 of Human Parturition

  • Strong uterine contractions postpartum mediated by PGFα2 facilitating placental separation.

  • Hemorrhage risk minimized via vasoconstrictor prostaglandins and uterine contraction minimizing blood loss (~350 ml).

  • Uterine involution supported by lactation, returning to pre-pregnancy size in ~6 weeks.

Uterotonins/Uterotonics & Tocolytics

Uterotonins/Uterotonics

  • Induce or augment labor and control postpartum bleeding, e.g., Oxytocin, Prostaglandins.

  • Used in abortion procedures.

Tocolytics

  • Relax myometrium, prevent preterm labor, and delay birth by 1-2 days. Examples:

    • PR antagonist: Mifepristone

    • Calcium channel blockers: Nifedipine

    • β-mimetics: Terbutaline

    • Prostaglandin inhibitors: Indomethacin, COX2 inhibitors.

Mammary Gland Structure and Function

  • Branched epithelial organ organized into 15-20 lobes, involved in milk synthesis and secretion.

  • Composed of secretory and hormone-responsive cells surrounded by contractile myoepithelial cells for milk transport.

Development of Mammary Gland

  • Mammogenesis: Biphasic growth phase including:

    • Lactogenesis: Alveolar development and milk initiation.

    • Galactopoiesis: Maintenance of milk production.

    • Involution post-lactation.

Lactogenesis

Secretory Differentiation

  • Initiated by prolactin, with additional roles for progesterone and estrogen in mammary development.

Secretory Activation

  • Triggered by progesterone withdrawal post-partum, enhancing milk synthesis and ejection mechanisms.

Lactational Amenorrhea

  • Occurrence of amenorrhea in lactating mothers (25-30 weeks).

  • Prolactin levels inhibit ovulation and menstrual cycle resumption.

  • Utilized as a natural family planning method but not a reliable contraceptive.

Colostrum vs. Mature Milk

  • Colostrum: Rich in proteins and immunological agents, crucial for newborn immunity.

  • Mature milk: Composed of lactose, casein, and triglycerides, providing essential nutrients for infant health.

Conclusion

  • Comprehensive understanding of parturition, lactation mechanisms, hormone effects, and their physiological roles are critical for maternal-infant health and welfare.