A luteal phase deficiency model in normal women: structural and functional responses to varying concentrations of progesterone

ABSTRACT: Progesterone (P) action is essential for embryo implantation, but the P concentration required for normal receptivity remains unclear. We use an in vivo model in normal women that abolishes detectable endogenous P production, allowing experimental provision of P. Endometrial samples on the 10th day of varying doses of P exposure are compared structurally and functionally with each other and with mid-secretory endometrium of natural cycles, using histological and microarray analysis. At 2.5mg/day of P, a delayed appearance of morphological features is seen. Higher sub-physiological levels of P result in normal morphology, but aberrant gene expression. These studies prove that low P levels can result in histological delay, consistent with clinical expectations. However, P levels required for consistent histological delay are lower than those seen in all ovulatory women. These studies also demonstrate that gene expression abnormalities can occur at higher sub-physiological P concentrations, without a change in morphology, a functional-morphological disassociation. The expression of some endometrial receptivity associated genes is multiphasic, with peak expression between the lowest and highest doses, suggesting sustained supraphysiological doses seen in fertility treatment cycles may not be optimal. These findings provide a scientific underpinning to previous studies that questioned the value of endometrial morphology as a marker for receptive endometrium and suggest potential new strategies for understanding endometrial P action. Total RNA obtained endometrium of women treated with progesterone at different doses (2.5 mg (n=4); 5 mg (n=4); 10mg (n=5_); 40 mg (n=5); Control no drug (n=9))

ORGANISM(S): Homo sapiens

SUBMITTER: Ricardo Savaris 

PROVIDER: E-GEOD-56980 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress