Oil-Soluble Contrast Medium (OSCM) for Hysterosalpingography Modulates Dendritic Cell and Regulatory T Cell Profiles in the Peritoneal Cavity: A Possible Mechanism by Which OSCM Enhances Fertility

Abstract

Hysterosalpingography (HSG) with oil-soluble contrast medium (OSCM) is known to enhance fertility, although the mechanism is unclear. OSCM remains in the peritoneal cavity for several months after HSG. We hypothesized that OSCM that remains in the peritoneal cavity modulates dendritic cell (DC) and regulatory T cell (Treg) profiles and contributes to enhanced fertility. We characterized the profiles of DCs and Tregs in the peritoneal fluid from women who had undergone HSG. In vitro and in vivo effects of OSCM on monocyte-derived DCs and mouse peritoneal T cells were also evaluated. In comparison with women who have never experienced HSG, samples from women who had undergone HSG contained myeloid DCs with greater complexity and maturation, as well as had a marginally greater proportion of Tregs in their peritoneal fluid. OSCM is incorporated by monocyte-derived DCs, which causes their maturation and contributes to the increase in Treg proportions. Samples from OSCM-injected mice contained greater proportions of Tregs in comparison with controls. These studies demonstrate that OSCM modulates T cell profiles that are compatible with the condition observed in women who have undergone HSG. This study demonstrates that exogenous lipids administered to the peritoneal cavity are incorporated by DCs and that they significantly alter the immune environment in the peritoneal cavity. This immunological impact may contribute to enhanced fertility and the development of alternative therapeutic strategies for managing other pathological conditions associated with immunological abnormalities in the peritoneal cavity.

Effectiveness on fertility outcome of tubal flushing with different contrast media: systematic review and network meta‐analysis

“…A debate about the therapeutic effects of tubal flushing started over six decades ago. Several potential mechanisms have been proposed to explain such therapeutic effects, including mechanical flushing out of the debris or mucus plugs in the Fallopian tubes, enhancement of ciliary activity and immunobiological actions on the endometrium or peritoneum.…”

Tubal flushing with oil- or water-based contrast medium: can we identify markers that indicate treatment benefit?

“…The underlying mechanism of the fertility-enhancing effect of flushing with oil-based contrast medium is unknown. Various studies suggest an immunobiological effect of the oil on the endometrium and the peritoneum (Izumi et al , 2017, Johnson, 2005, Johnson, 2014, Mikulska et al , 1994, Sawatari et al , 1993, Yun and Lee, 2004) or enhancement of the tubal ciliary activity (Soules and Spadoni, 1982). Another potential explanation is a mechanical effect, during tubal patency testing with oil-based contrast medium debris or mucus plugs flushes out of the fallopian tubes (Gillespie, 1965).…”

Randomised Trial of Lipiodol Uterine Bathing Effect (LUBE) in Women with Endometriosis-Related Infertility

“…Osteopontin was the only gene transcript that was regulated in the endometrium of all women exposed to lipiodol, osteopontin being down-regulated. Of the three predominating theories for the mechanism of lipiodol fertility enhancement -that lipiodol is an effective 'flushing agent' of amorphous debris from fallopian tubes (Watson et al, 1994); that it alters peritoneal immuno-biology through an increase in regulatory T-cells apparently mediated by a change in the activation status of mature myeloid dendritic cells due to incorporation of lipiodol by these dendritic cells (Saidi et al, 2004); that it may act through a uterine bathing effect which improves endometrial receptivity (Johnson, 2005;Johnson, 2014;Izumi et al, 2017) -this study goes some way to supporting the latter uterine bathing theory. An immuno-biological effect of lipiodol is supported by the more dramatic short term effect on fertility among women with endometriosis (Johnson et al, 2004) and an endometrial effect is further supported by our murine study that showed an increase in endometrial activated dendritic cells in mice exposed to lipiodol (Johnson et al, 2005).…”