Intermittent fasting dietary restriction regimen negatively influences reproduction in young rats: a study of hypothalamo-hypophysial-gonadal axis

PLoS One. 2013;8(1):e52416. doi: 10.1371/journal.pone.0052416. Epub 2013 Jan 29.


Nutritional infertility is very common in societies where women fail to eat enough to match their energy expenditure and such females often present as clinical cases of anorexia nervosa. The cellular and molecular mechanisms that link energy balance and central regulation of reproduction are still not well understood. Peripheral hormones such as estradiol, testosterone and leptin, as well as neuropeptides like kisspeptin and neuropeptides Y (NPY) play a potential role in regulation of reproduction and energy balance with their primary target converging on the hypothalamic median eminence-arcuate region. The present study was aimed to explore the effects of negative energy state resulting from intermittent fasting dietary restriction (IF-DR) regimen on complete hypothalamo-hypophysial-gonadal axis in Wistar strain young female and male rats. Significant changes in body weight, blood glucose, estrous cyclicity and serum estradiol, testosterone and LH level indicated the negative role of IF-DR regimen on reproduction in these young animals. Further, it was elucidated whether serum level of metabolic hormone, leptin plays a mechanistic role in suppressing hypothalamo-hypophysial-gonadal (HPG) axis via energy regulators, kisspeptin and NPY in rats on IF-DR regimen. We also studied the effect of IF-DR regimen on structural remodeling of GnRH axon terminals in median eminence region of hypothalamus along with the glial cell marker, GFAP and neuronal plasticity marker, PSA-NCAM using immunostaining, Western blotting and RT-PCR. Together these data suggest that IF-DR regimen negatively influences reproduction in young animals due to its adverse effects on complete hypothalamus-hypophysial-gonadal axis and may explain underlying mechanism(s) to understand the clinical basis of nutritional infertility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anorexia Nervosa / etiology
  • Anorexia Nervosa / physiopathology*
  • Estradiol / blood
  • Estrous Cycle
  • Fasting / adverse effects*
  • Female
  • Gonads / metabolism
  • Humans
  • Hypothalamus / metabolism
  • Infertility, Female / blood
  • Infertility, Female / complications
  • Leptin / blood
  • Male
  • Neuronal Plasticity
  • Neurons / metabolism
  • Neuropeptide Y / metabolism*
  • Pituitary Gland / metabolism
  • Rats
  • Rats, Wistar
  • Reproduction / genetics
  • Reproduction / physiology*
  • Testosterone / blood


  • Leptin
  • Neuropeptide Y
  • Testosterone
  • Estradiol

Grants and funding

The study was supported by a Grant from the Indo-French Centre for Promotion of Advanced Research (IFCPAR) and Indian Council of Medical Research (ICMR) under the National Task Force Program. Mr. Sushil Kumar is thankful to the IFCPAR, New Delhi for the research fellowship provided during this research work. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.