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Epigenetics of functional hypothalamic amenorrhea.

L Fontana1,2, E Garzia3,4, G Marfia4,5

  • 1Medical Genetics, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy.

Frontiers in Endocrinology
|August 29, 2022
PubMed
Summary

Genetic and epigenetic factors influence functional hypothalamic amenorrhea (FHA), a temporary infertility. Understanding these individual differences in the reproductive axis response to stress is key to FHA research.

Keywords:
anorexia nervosadelayed pubertyepigeneticsfunctional hypothalamic amenorrhea (FHA)susceptibility genes

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Area of Science:

  • Reproductive Endocrinology
  • Neuroendocrinology
  • Genetics

Background:

  • Functional hypothalamic amenorrhea (FHA) involves temporary infertility due to hypothalamic-pituitary-gonadal (HPG) axis suppression.
  • Stressors like eating disorders, excessive exercise, and psychological distress inhibit gonadotropin-releasing hormone (GnRH) secretion, leading to FHA.
  • Inter-individual variability in FHA development suggests underlying genetic and epigenetic influences.

Purpose of the Study:

  • To review recent advances in understanding the genetic and epigenetic contributions to FHA.
  • To explore the role of genetic variants in GnRH neuron function and reproductive axis adaptability to stress.
  • To highlight the potential of induced pluripotent stem cells (iPSCs) in FHA research.

Main Methods:

  • Literature review of recent studies on (epi)genetics and FHA.
  • Analysis of clinical and molecular overlaps between FHA and other gynecological/psychological conditions.
  • Discussion of induced pluripotent stem cell (iPSC) applications.

Main Results:

  • Genetic variants in GnRH neuron-related genes may influence stress response and FHA susceptibility.
  • Epigenetic modifications are associated with HPG axis pathways and may confer predisposition or serve as stress response markers.
  • Clinical and molecular similarities suggest shared genetic loci between FHA and other conditions.

Conclusions:

  • Genetics and epigenetics play a significant role in FHA development and long-term complications.
  • Further research into genetic loci and epigenetic mechanisms is crucial for understanding FHA.
  • iPSCs offer a promising avenue for investigating FHA's molecular underpinnings.