
Faculty, Staff and Student Publications
Publication Date
3-1-2022
Abstract
Female mice homozygous for an engineered Gnrhr E90K mutation have reduced gonadotropin-releasing hormone signaling, leading to infertility. Their ovaries have numerous antral follicles but no corpora lutea, indicating a block to ovulation. These mutants have high levels of circulating estradiol and low progesterone, indicating a state of persistent estrus. This mouse model provided a unique opportunity to examine the lack of cyclic levels of ovarian hormones on uterine gland biology. Although uterine gland development appeared similar to controls during prepubertal development, it was compromised during adolescence in the mutants. By age 20 weeks, uterine gland development was comparable to controls, but pathologies, including cribriform glandular structures, were observed. Induction of ovulations by periodic human chorionic gonadotropin treatment did not rescue postpubertal uterine gland development. Interestingly, progesterone receptor knockout mice, which lack progesterone signaling, also have defects in postpubertal uterine gland development. However, progesterone treatment did not rescue postpubertal uterine gland development. These studies indicate that chronically elevated levels of estradiol with low progesterone and therefore an absence of cyclic ovarian hormone secretion disrupts postpubertal uterine gland development and homeostasis.
Keywords
Animals, Chorionic Gonadotropin, Estradiol, Estrus, Female, Infertility, Female, Mice, Mice, Knockout, Ovarian Follicle, Ovulation, Progesterone, Receptors, LHRH, Uterus
DOI
10.1210/endocr/bqac011
PMID
35134138
PMCID
PMC8852258
PubMedCentral® Posted Date
2-3-2022
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Endocrinology, Diabetes, and Metabolism Commons, Medical Sciences Commons, Oncology Commons