(182) Preconceptional innate immunomodulation leads to a partial correction of gestational complications induced by endometriosis in a murine model

K. Bouzid¹ ; A. Silvert² ; R. Bartkowski¹ ; P. Santulli³ ; L. Marcellin³ ; F. Batteux¹ ; C. Mehats¹ ; L. Doridot¹

1. Institut Cochin, Inserm, Université Paris Cité, CNRS, Paris, France
2. iPOP-UP, Université Paris Cité, Paris, France
3. Department of Gynaecology Obstetrics II and Reproductive Medicine, Cochin Hospital, AP-HP Centre-Université Paris Cité, Paris, France

Abstract Text:

Endometriosis is a common chronic gynecological disease affecting women of childbearing age. It can cause pain, infertility, and increases the risk of pregnancy complications such as miscarriages, low birth weight, and premature delivery. The mechanisms underlying these pregnancy complications remain poorly understood. We hypothesize that the inflammatory environment and altered eutopic endometrium are detrimental to normal pregnancy progression.

Our team previously demonstrated in a mouse model of endometriosis that immunomodulatory treatment with low-dose lipopolysaccharide (LPS) limits disease-associated inflammation and reduces lesion size. Here, we show that this mouse model exhibits gestational complications: compared to controls, endometriosis reduces the mean number of implantation sites by 10% (p = 0.07) and doubles the percentage of fetal resorptions (p < 0.01). Importantly, LPS treatment corrects these deficits, resulting in no significant difference in the number of implantation sites or resorption rates compared to controls. This study aims to understand the immunomodulatory effects of low-dose LPS on endometriosis-induced gestational complications.

We present a single-nucleus/cell transcriptomic analysis of early placentas (E9.5) in the context of endometriosis and endometriosis with preconceptional LPS treatment, focusing on the immune landscape. Our results demonstrate that LPS treatment partially reverses the transcriptomic changes caused by endometriosis, specifically correcting the disease-induced inflammatory transcriptomic profile. We will also present a transcriptomic analysis of cell-cell interactions within these early placentas.

This study help us better understand the implantation and pregnancy complications induced by endometriosis, and hopefully we will find mecanisms in common between mouse and human. We know that around 40% of women with endometriosis face infertility and when they finally get pregnant, they face a higher risk of pregnancy complications. Understanding this will be part of the whole scientific and medical effort to help the couples who want to have children with a partner having endometriosis.