P–641 Pubertal high-fat diet interferes with the ovarian kisspeptin ligand and receptor expressions regulating female fertility
Authors: Doğan M , Kılınç L , Sinen O , Bülbül M , Akkoyunlu G 
Published: August 2021

Abstract

Study question
Does chronic high-fat diet affect ovarian dysfunctions via changing of kisspeptin and kisspeptin receptor expressions?

Summary answer
Ovarian kisspeptin and kisspeptin receptor expressions are significantly affected by the chronic high-fat diet.

What is known already
Regarding the hypothalamic-pituitary-gonadal (HPG) roles of kisspeptin, it appears that it directly stimulates LH secretion from the pituitary, consecutively stimulates ovulation in the female. There are also studies showing that kisspeptins can increase GnRH release, serum FSH, LH, and testosterone (in vivo), and regulate ovulation in women who have reached sexual maturity through the central control of the HPG axis.
Fatty acids can act as nutritional signals that regulate the HPG axis, and elevated levels of circulating saturated fatty acids associated with high-fat diet (HFD)-feeding has been shown to induce ovarian dysfunction. HFD consumption induces ovarian dysfunction in rodents.

Study design, size, duration
4-week-old female rats obtained from Akdeniz University Experimental Animals Unit. Animals were kept in standard conditions; fed with control diet consisting of standard laboratory food (13.5% of total energy from oil) or HFD (60% of total energy from oil) for 8 weeks. Experimental procedures were performed at the age of 12 weeks (250–275 g live weight). Live weights and food consumption of the animals in both groups were calculated weekly and recorded during the experiment.

Participants/materials, setting, methods
At the end of the experimental period, the animals were sacrificed and tissues were obtained. Sections were taken from paraffin-embedded tissues. Immunohistochemical staining for KISS1 and GPR54 were performed in both groups’ ovaries. Tissue collecting, processing, and immunohistochemical staining were performed at the histology and embryology department of Akdeniz University Faculty of Medicine.

Main results and the role of chance
There was a significant increase in body weights of the HFD group during the experiment period compared to the control group.
As a result of immunohistochemical staining, kisspeptin expression is specifically localized to the corpora lutea of the control ovaries. However, kisspeptin expression in the corpora lutea of the HFD ovaries was increased regardless of the ovarian follicles.
KISS1R expression was located in the cytoplasm of oocytes. HFD group also expressed the KISS1R in the oocytes with increasing intensity.

Limitations, reasons for caution
The study design included pubertal age limit of the samples. The functional reproductive period in different mammal species should be considered.
Wider implications of the findings: We suggest that chronic exposure of female rats to a high-fat diet may induce ovarian Kisspeptin expression while kisspeptin receptor expression is not affected in oocytes. Clinical implications should be considered.

Trial registration number
B.30.2.AKD.0.05.07.00/99