A pilot in vivo study: potential ovarian cancer therapeutic by placental extracellular vesicles.

The biological links between cancer and pregnancy are of interest due to parallel proliferative, immunosuppressive, and invasive mechanisms between tumour and placental cells. However, the proliferation and invasion of placental cells are strictly regulated. The understanding of this regulation is largely unknown. Placental extracellular vesicles (EVs) may play an important role in this regulation, as placental EVs are known to contribute to maternal adaptation, including adaptation of the vascular and immune systems. We have previously reported that placental EVs significantly inhibited ovarian cancer cell proliferation by delaying the progression of the cell cycle. We, therefore, performed this pilot in vivo study to investigate whether placental EVs can also inhibit ovarian tumour growth in a SKOV-3 human tumour xenograft model. A single intraperitoneal injection of placental EVs at 15 days post tumour implantation, significantly inhibited the growth of the tumours in our in vivo model. Signs of cellular necrosis were observed in the ovarian tumour tissues, but not in other organs collected from mice that had been treated with placental EVs. Expression of receptor-interacting kinase 1 (RIPK1) and mixed linkage kinase domain-like (MLKL), which are mediators of necroptosis were not observed in our xenografted tumours. However, extensive infiltration of CD169+ macrophages and NK cells in ovarian tumour tissues collected from placental micro-EVs treated mice were observed. We demonstrate here that inhibition of ovarian tumour growth in our xenograft model by placental EVs involves cellular necrosis and infiltration of CD169+ macrophages and NK cells into the tumour tissues.

Human seminal plasma prolactin-inducible protein is an immunoglobulin G-binding protein.

Antisperm antibodies (ASA) are present in 20% of couples seeking treatment for infertility. Antibody-binding proteins in seminal plasma may protect sperm from ASA-induced damage. We have previously isolated several IgG-binding proteins from human seminal plasma using IgG affinity chromatography. Here, we report another such protein which we have identified by amino acid sequencing and confirmed by western blotting to be prolactin-inducible protein (PIP). PIP binds via the Fc fragment of IgG. We have determined the level of PIP in normal seminal plasma to be 3.4 mg/ml (interquartile range 2.0-4.4 mg/ml). We have found there is no difference in the mean level of PIP in seminal plasma from fertile or infertile men regardless of ASA status. PIP was shown to exist in several isoforms in seminal plasma by Western blot. There is a complex pattern of PIP isoform variability in seminal plasma from fertile and infertile men but one multimeric form of PIP was absent from the seminal plasma of men with ASA who were fertile. This may reflect consumption of PIP in these men. The physiological function of PIP remains unknown, but the ability of PIP to bind IgG-Fc suggests PIP may have an immunomodulatory role.

Lipiodol alters murine uterine dendritic cell populations: a potential mechanism for the fertility-enhancing effect of lipiodol.

OBJECTIVE: To determine whether treatment with lipiodol alters the leukocyte population in the uterus. DESIGN: Randomized controlled animal study. SETTING: University research laboratory. ANIMAL(S): Sixty female Swiss white mice at proestrous. INTERVENTION(S): Infusion of the female reproductive tract with lipiodol versus infusion with saline versus sham treatment. MAIN OUTCOME MEASURE(S): Counts of uterine macrophages, dendritic cells, and total leukocytes assessed by immunohistochemistry. RESULT(S): No statistically significant differences were found in the mean number of total leukocytes or macrophages between the three treatment groups. The mean number of CD205+ dendritic cells showed a statistically significant decrease following lipiodol treatment compared with the sham treatment and saline treatment. The mean number of CD1+ dendritic cells showed a statistically significant increase following lipiodol treatment compared with the sham treatment. CONCLUSION(S): Intrauterine lipiodol infusion is associated with a change in the uterine dendritic cell populations in mice. This change may alter the uterine immune response to the fetus, leading to improved fertility.