ABSTRACT
BACKGROUND: Leptin serves as a signal to the central nervous system with information on the critical amount of adipose tissue stores that is necessary for activation of the hypothalamic-pituitary-ovarian axis. OBJECTIVES: To document the histological and ultrastructural changes that occur in the ovarian follicles of immature albino rats treated with leptin when compared with controls. Furthermore, the endometrial histological and immunohistochemical, and vaginal cytological changes suggestive of ovulation were assessed. ANIMALS AND METHODS: The study was carried out on 50 immature female albino rats aged 22 days; 24 of them were injected with 5 microg leptin daily and 26 rats were taken as controls. Vaginal smears were taken daily, three animals were sacrificed every 2-4 days from each group, ovaries and uteri were dissected and specimens were prepared for electron microscopic, histological and/or immunohistochemical assessment. The research project was approved by The Histology Department Committee of Alexandria Medical School, which is licensed for animal care and use. RESULTS: Electron microscopic and histological examination confirmed the occurrence of maturational changes in various ovarian components from 26 days of age in leptin-treated rats, with ovulation occurring from the age of 30 days. The granulosa, theca and stroma cells showed signs of steroidogenesis, with increased mitosis within granulosa cells. The ooplasm showed an increased number of organelles, and annulate lamellae were demonstrated. The zona pellucida revealed microvilli, adhering junctions and gap junctions. Similarly, the endometrial histological and vaginal cytological maturational changes were detected in leptin-treated rats from 26 days of age. Furthermore, there was high expression of estrogen receptor-alpha in almost all columnar and stroma cells of the endometrium. However, the control rats ovulated around the normal age of maturation, i.e. 42 days. CONCLUSION: We documented ultrastructural, histological, immunohistochemical and cytological evidence that leptin accelerates the onset of puberty in female albino rats. The potential role of exogenous leptin, in cases of impaired reproductive function in humans, needs to be elucidated.
