Abstract
The ovarian reserve is an important factor influencing female reproduction and fertility health. The ovarian reserve consists of primordial follicles that are important in determining the length of fertility in a woman’s lifetime. During puberty, animals show a large loss in their number of primordial follicles, and therefore the age of pubertal onset may be a determinant of the ovarian reserve in adult life. The ovary itself is part of the hypothalamus-pituitary-gonad (HPG axis) system that controls puberty and reproduction. The HPG axis is crucial for pubertal onset and production of steroid hormones that control the ovary's folliculogenesis.
This study aimed to manipulate the age at puberty and assess changes in the ovarian reserve through two approaches: the first was to develop a transgenic mouse model that, through treatment with deschloroclozapine would cause inhibition of kisspeptin secretion, would delay puberty onset; the second was to use a GnRH antagonist (degarelix) that is already known to delay puberty in female rodents. Once a delay in puberty was established, we would assess changes in the ovarian reserve compared to control mice.
The transgenic mice model failed to delay puberty onset, and this project was therefore put on hold. The GnRH antagonist significantly delayed pubertal onset in terms of vaginal opening and first estrus in female mice. Estrus cyclicity after the first estrus in female mice treated with the GnRH antagonist was initially dysregulated in the treatment group, but this resolved after 10 days. At euthanasia, the ovaries of treated mice were significantly smaller than in control mice, but there was no difference in the number of primordial follicles between groups. Based on the results, we can conclude that the GnRH antagonist influences pubertal onset but does not influence the ovarian reserve in female mice.
Understanding the long-term physiological impacts of GnRH antagonists is important, as these drugs are frequently used in women with cancer, issues in puberty, assisted reproduction, and gender identity. These drugs are used in hopes of delaying or stopping puberty, with little to no knowledge of how they influence the gonads in terms of the process of folliculogenesis and the ovarian reserve.