The nutritional environment during development periods induces metabolic programming
leading to metabolic disorders and detrimental influences on human reproductive health. This study aimed to determine the long-term adverse effect of intrauterine malnutrition on the reproductive center kisspeptin-neurokinin B-dynorphin A (KNDy) neurons in the hypothalamic arcuate nucleus (ARC) of female offspring. Twelve pregnant rats were divided into ad-lib-fed (control
n = 6) and 50% undernutrition (UN
n = 6) groups. The UN group was restricted to 50% daily food intake of the control dams from gestation day 9 until term delivery. Differences between the two groups in terms of various maternal parameters
including body weight (BW)
pregnancy duration
and litter size
as well as birth weight
puberty onset
estrous cyclicity
pulsatile luteinizing hormone (LH) secretion
and hypothalamic gene expression of offspring
were determined. Female offspring of UN dams exhibited low BW from birth to 3 weeks
whereas UN offspring showed signs of precocious puberty; hypothalamic Tac3 (a neurokinin B gene) expression was increased in prepubertal UN offspring
and the BW at the virginal opening was lower in UN offspring than that in the control group. Interestingly
the UN offspring showed significant decreases in the number of KNDy gene-expressing cells after 29 weeks of age
but the number of ARC kisspeptin-immunoreactive cells
pulsatile LH secretions
and estrous cyclicity were comparable between the groups. In conclusion
intrauterine undernutrition induced various changes in KNDy gene expression depending on the life stage. Thus
intrauterine undernutrition affected hypothalamic developmental programming in female rats.
