First Advisor

Hydock, David

Document Type

Dissertation

Date Created

5-2023

Abstract

The number of adolescents identifying as transgender has been increasing with many transgender youth receiving treatment with a gonadotropin releasing hormone agonist (GnRHa) that suppresses sex hormone production (i.e., puberty blocker). Transgender individuals taking a GnRHa to block puberty have reported improved mental wellbeing, but the physiological impacts need to be examined. Purpose: To investigate the effects of puberty blocking treatment using GnRHa on physical activity, reproductive morphology, and reproductive function in young female rats. Methods: Four-week old female Sprague Dawley rats were given daily subcutaneous injections of the GnRHa triptorelin or saline as control. One group of rats was housed in cages outfitted with a voluntary running wheel to monitor physical activity while treatment continued for 4-weeks. At eight weeks old, non-wheel running rats were euthanized and the uterus and ovaries were removed for H&E staining or flash frozen to assess morphology and DNA methylation. An additional group was taken off GnRHa treatment for 4-weeks to examine recovery of reproductive organ morphology and DNA methylation. The final group was taken off GnRHa treatment and housed with fertile males to determine reproductive performance. Results: Animals treated with the GnRHa had a significant reduction in total wheel running distance. Daily wheel running analysis showed a significant main drug effect, main time effect, and time x drug interaction. The reduction of wheel running activity began on day-5 and continued until the final day-28. The puberty blocked rats also had a significantly greater body mass than controls. GnRHa treatment led to a reduction in the mass of uteri and ovaries which recovered after 4-weeks of drug withdrawal. The myometrial and endometrial thickness of the uterus was reduced in GnRHa treated animals. The ovaries of puberty blocked animals exhibited a disruption in follicle development and corpora lutea health. The morphology of the uterus and ovaries recuperated after 4-weeks of drug withdrawal. With respect to reproductive performance, no significant difference in pregnancy rate was detected; however, both the number of days until pregnancy detection and number of days until giving birth were considerably longer in GnRHa rats following withdrawal. The number of pups per litter was also significantly reduced by puberty blocking treatment but no abnormalities were observed in the pups. Conclusion: Young female rats treated with a GnRHa had significantly reduced voluntary wheel running, increased body mass, and developmental delay of the reproductive organs. After 4 weeks of GnRHa withdrawal reproductive organ mass and morphology recovered. A minor disruption in reproductive function was detected immediately following GnRHa withdrawal. These physiological effects on physical activity and reproductive health should be considered when administering a GnRHa to block puberty.

Extent

112 pages

Local Identifiers

Jones_unco_0161D_11114.pdf

Rights Statement

Copyright is held by the author.

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