Long-term effects of prenatal undernutrition on female rat hypothalamic KNDy neurons.

Shiori Minabe
Kinuyo Iwata
Youki Watanabe
Hirotaka Ishii
Hitoshi Ozawa

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.

Endocrine connections

10.1530/EC-22-0307

https://doi.org/10.1530/EC-22-0307
https://www.ncbi.nlm.nih.gov/pubmed/36408965