Chronic Estrus Disrupts Uterine Gland Development and Homeostasis

C. Allison Stewart, M. David Stewart, Ying Wang, Rachel D. Mullen, Bonnie K. Kircher, Rui Liang, Yu Liu, Richard R. Behringer

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish (US)
Article numberbqac011
JournalEndocrinology
Volume163
Issue number3
DOIs
StatePublished - Mar 1 2022

Keywords

  • GnRHR
  • adenogenesis
  • endometrium
  • estrogen
  • hydrometria
  • progesterone

ASJC Scopus subject areas

  • Endocrinology

MD Anderson CCSG core facilities

  • Genetically Engineered Mouse Facility

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