Dynamic expression of endometrial adhesion G protein-coupled receptors during the menstrual cycle and early mouse pregnancy: modulation by ovarian stimulation

Objective

To characterize the expression of adhesion G protein-coupled receptors (ADGR) in the human endometrium and early mouse pregnancy.

Design

An in silico analysis was performed using a retrospective data set comprised endometrial samples across normo-ovulatory menstrual cycles. Gene expression was then validated using quantitative reverse transcription polymerase chain reaction and mRNA sequencing (mRNA-seq) in prospectively collected endometrial biopsies in the periovulatory and midsecretory stages of natural cycles. Gene expression was also investigated under ovarian stimulation (OS) conditions using mRNA-seq. Early pregnancy mouse models were used to investigate whether trends of dynamic ADGR expression are also conserved in the mouse.

Subjects

Twenty-four women aged 21–42 years.

Exposure

Ovulatory menstrual cycle or OS cycle.

Main Outcome Measures

Gene expression in endometrial biopsies and pregnant mouse uterus.

Results

Fifteen women, aged 21–33 years, were recruited in natural cycles during the proliferative phase (cycle days 10–13; n = 4), periovulatory (luteinizing hormone + 12–24 hours; n = 6) period, and midsecretory (luteinizing hormone + 8–9 days; n = 5) phase. Nine women aged 31–42 years old undergoing in vitro fertilization (without fresh embryo transfer) or oocyte cryopreservation using a gonadotropin releasing hormone antagonist protocol were recruited for the OS cohort in either the periovulatory phase (human chorionic gonadotropin + 2; n = 5) or midsecretory phase (human chorionic gonadotropin + 9; n = 4). The in silico analysis revealed dynamic expression for many ADGRs across the menstrual cycle. Differential gene expression was also seen in the prospective analysis within the menstrual cycle phases and between natural cycle and OS conditions. Within early mouse pregnancy, expression was also found to be altered across several Adgr subfamilies.

Conclusion

The differential gene expression observed between the proliferative and secretory phases of the menstrual cycle, along with changes in expression seen in OS and early mouse pregnancy suggest that ADGR expression is hormonally regulated by estradiol and progesterone.