Abstract
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.
Highlights
Animals adjust their energy requirements when food is scarce or have a very high acquisition cost [1] and under metabolic stress, all the animals invest energy in survival rather than reproduction
To further investigate whether change in energy status due to intermittent fasting dietary restriction (IF-DR) regimen negatively influence the reproductive function in rats at the level of these central regulatory mechanisms as well, we explored the effect of IF-DR regimen on gonadotropin releasing hormone (GnRH) axon terminals remodeling in median eminence (ME) region of hypothalamus in both male and female rats alongwith the expression of plasticity markers such as PSA-NCAM and GFAP
IF-DR regimen adversely affected the reproductive function as evident from disrupted estrous cycle and reduced ovarian weight observed in IFDR female rats as compared to ad libitum (AL) fed control animals, which showed normal estrous cyclicity
Summary
Animals adjust their energy requirements when food is scarce or have a very high acquisition cost [1] and under metabolic stress, all the animals invest energy in survival rather than reproduction. The reproductive system is sensitive to change in energy status [1] but the physiological mechanisms explaining the link between energy balance and reproduction are not clearly understood. Food restriction has been known to exert negative influence on luteinizing hormone (LH) pulsatility in prepubertal or cycling gilts [4], on ovarian development [5] and decrease in gonadotropin concentration in humans [6] Both gonadotropin releasing hormone (GnRH) pulse generator system and gonadotropin secretion are inhibited by food restriction and the gonadotropin effect for folliculogenesis may not be sufficient [7,8]. Understanding the physiological basis of joint regulation of energy balance and reproductive function could help to design better strategies for maintaining reproductive health
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