P-805 Gene expression of human endometrial organoids hormonally treated in vitro for 28 days

Abstract Study question Does gene expression of human endometrial organoids (EO) mimic the in vivo response to a 28- days substitutive hormonal treatment? Summary answer Gene profile EO exposed 28-day hormone treatment showed correspondence with phases menstrual cycle vivo. What is known already The recent development demonstrated their translational potential for reproductive medicine. Current studies testing functional hormones are based on short-term responsiveness estrogen (E2), progesterone (P4) and differentiation factors up 10 days. It unknown how can be used faithfully reproduce and/or model complete 28 High-throughput analyses endometrium have identified specific markers available characterizing aspects related secretory activity receptivity implantation. design, size, duration Experimental research was carried out including 4 biopsies donated by women normal function, recruited at an academic center assisted reproduction between 2022-06-15 2022-07-28. These were processed organoid derivation culture. hormonally treated vitro analyzed expression. Participants/materials, setting, methods Human enzymatically digested isolate glands, embedded matrigel cultivated spinning bioreactor achieve formation. Thereafter as following: 1) E2: (day 0–28); 2) E2 + P4: 0–28), P4 14–28); 3) dibutyryl cyclic Adenosine monophosphate (dbcAMP): 0–28) 14–28) dbcAMP or 4) control group. Main results role chance A total selected analysis 3 pattern interest. target included Forkhead box O1 (FOXO1), involved regulating human; associated protein (PAEP), major glandular secretions; secreted phosphoprotein 1 (SPP1), extracellular cytokine that increases during receptive phase. FOXO1, PAEP SPP1 significant increase cycle, compared controls. lower day 21 but upregulated 15-fold relative non-treated group 28. This recapitulates similar physiological conditions endometrium. Although patterns followed trends, individual had slight variations along treatment. day-hormone stimulate recapitulating histological aspects. dynamics resembled timely correlation changes accounting some mostly receptivity, thus reinforcing application further purposes. Limitations, reasons caution In culture may influence over requires optimization uterine environment other infertility completely defined system. Wider implications findings Our enable opportunity expand experimental disorders affecting different stages also improve embryo-endometrium interactions. Trial registration number has been funded grants from Swedish Cancer Society, Childhood Foundation, Research Funds Radiumhemmet, Association BRO, Stockholm County Council (CIMED) Karolinska Institutet.