Related Experiment Video

Updated: May 11, 2026

Using a Murine Model of Psychosocial Stress in Pregnancy as a Translationally Relevant Paradigm for Psychiatric Disorders in Mothers and Infants
06:39

Using a Murine Model of Psychosocial Stress in Pregnancy as a Translationally Relevant Paradigm for Psychiatric Disorders in Mothers and Infants

Published on: June 13, 2021

Spontaneous miscarriages are explained by the stress/glucocorticoid/lipoxin A4 axis

Zhangye Xu1, Jie Zhao, Huafeng Zhang

  • 1Department of Gynecology and Obstetrics, First Affiliated Hospital, Wenzhou Medical College, Wenzhou 325003, People's Republic of China.

Journal of Immunology (Baltimore, Md. : 1950)
|May 17, 2013
PubMed

Insights

Miscarriage may be caused by decreased lipoxin A4 (LXA4), a pregnancy-protective molecule. Stress reduces LXA4 by altering an enzyme that inactivates glucocorticoids, leading to pregnancy loss.

Area of Science:

  • Reproductive immunology
  • Molecular endocrinology
  • Inflammation biology

Background:

  • The molecular mechanisms underlying miscarriage remain largely unknown.
  • Suspected causes include endocrine, genetic, infectious, and immunological factors.
  • 11β-hydroxysteroid dehydrogenase (HSD) type 2 is crucial for inactivating glucocorticoids during pregnancy.

Purpose of the Study:

  • To elucidate the molecular mechanisms of early pregnancy loss.
  • To investigate the role of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) and lipoxin A4 (LXA4) in miscarriage.
  • To identify a common molecular pathway involved in stress-induced pregnancy loss.

Main Methods:

  • Analysis of 11β-HSD2, glucocorticoid activity, and LXA4 levels in women with spontaneous miscarriages and a murine model.
  • Investigating the effects of LXA4 replenishment and blockade on pregnancy outcomes in mouse models.
  • Examining the impact of stress and infection on the expression of 11β-HSD2 and 11β-HSD1.

Main Results:

  • Downregulation of 11β-HSD2 was observed in women with miscarriage and in a murine model.
  • Decreased levels of LXA4 and its biosynthetic enzymes were found in spontaneous miscarriages.
  • Restoring LXA4 levels prevented LPS-induced miscarriage, while blocking LXA4 signaling induced miscarriage in mice.
  • Stress or infection led to decreased 11β-HSD2 expression, increased glucocorticoid activity, and reduced LXA4.

Conclusions:

  • The stress/glucocorticoid/LXA4 axis represents a potential common pathway for miscarriage.
  • 11β-HSD2 downregulation and subsequent LXA4 inhibition contribute to pregnancy loss.
  • LXA4 plays a protective role by modulating uterine and placental inflammation and mast cells.

More Related Videos

Multiplexed Fluorescent Immunohistochemical Staining of Four Endometrial Immune Cell Types in Recurrent Miscarriage05:16

Multiplexed Fluorescent Immunohistochemical Staining of Four Endometrial Immune Cell Types in Recurrent Miscarriage

Published on: August 4, 2021

Ex Vivo Placental Explant Flow Culture - Mimicking the Dynamic Conditions In Utero04:17

Ex Vivo Placental Explant Flow Culture - Mimicking the Dynamic Conditions In Utero

Published on: September 8, 2023

Related Concept Videos

Hypothalamic-Pituitary Axis01:37

Hypothalamic-Pituitary Axis

The response to stress—be it physical or psychological, acute or chronic—involves activation of the Hypothalamic-Pituitary-Adrenal (HPA) axis. The HPA axis is part of the neuroendocrine system because it involves both neuronal and hormonal communication. Its function is to regulate homeostatic systems—metabolic, cardiovascular, and immune—providing the necessary means to respond to a stressor.
Ovarian Cycle01:27

Ovarian Cycle

The menstrual cycle includes a critical component known as the ovarian cycle, which undergoes two main phases each month—the follicular phase and the luteal phase. The follicular phase is variable and averaging around 14 days. Ovulation, triggered by a surge in luteinizing hormone (LH), marks the transition between the two phases. The second phase, the luteal phase, is relatively consistent, lasting approximately 14 days, and is marked by the activity of the corpus luteum. While a cycle length...
Physiological Foundation of Stress01:24

Physiological Foundation of Stress

Stress triggers a coordinated physiological response involving the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis. This dual activation ensures that the body is prepared for both immediate and prolonged stress management. The process begins with the perception of a stressor. This initial phase activates the SNS, leading to the rapid release of adrenaline (epinephrine) from the adrenal glands.
Role of the Sympathetic Nervous System
Adrenaline triggers the...
Introduction to Stress and Lifestyle01:27

Introduction to Stress and Lifestyle

Stress is a multifaceted response to events perceived as challenging or threatening, highlighting physical, emotional, cognitive, and behavioral reactions. Physically, stress can lead to fatigue, sleep disruptions, and various health issues such as frequent colds, chest pains, and nausea. Emotionally, it can manifest as anxiety, depression, irritability, and anger triggered by both minor and major life events. Cognitively, it may result in difficulty in concentration, memory, and...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.