# Partial embryo loss caused by disruption of the placental hormone CTRP6 coincides with dNK cell abnormalities during pregnancy

## TL;DR

A placental hormone called CTRP6 is crucial for embryo survival, and its deficiency causes pregnancy issues by disrupting immune cells at the maternal-fetal interface.

## Contribution

The study reveals that CTRP6 deficiency causes partial embryo loss by impairing decidual NK cells, with potential for therapeutic intervention.

## Key findings

- C1qtnf6 is highly expressed in invasive placental cells and its deficiency leads to partial fetal loss.
- CTRP6 deficiency impairs decidual NK cell function and numbers at the maternal-fetal interface.
- Injecting CTRP6 rescues dNK cell abnormalities and reduces embryo loss.

## Abstract

The proper embryo maintenance depends on tight maternal-fetal communications. C1q/TNF-related protein 6 (C1qtnf6)—encoding a hormone-like CTRP6 protein—exhibits placenta-enriched expression and its deficiency causes partial fetal loss. Here, we demonstrate that abundant C1qtnf6 expression is distinctive for hemochorial placentae, which have deep uterine invasion. C1qtnf6 is most highly expressed in human extravillous trophoblasts and mouse spiral artery-associated trophoblast giant cells, which are functionally analogous cells that invade uterines. The partial embryo loss is mainly due to impaired CTRP6 production by placenta, and key natural killer effectors in maternal-fetal interface (MFI) are impaired by C1qtnf6-deficiency. C1qtnf6-deficiency simultaneously impairs the amount and effector production of decidual NK (dNK) cells, yet the placental structure and spiral artery remodeling appear normal. CTRP6 injection rescues the dNK cell abnormality and alleviates embryo loss. Overall, the partial embryo loss by CTRP6-deficiency coincides with dNK cell abnormality, which highlights the importance of MFI immune microenvironment for embryo maintenance.

•Abundant C1qtnf6 expression is distinctive for hemochorial placentae•Impaired placental-secretion of CTRP6 causes partial embryo lethality•C1qtnf6-deficiency leads to multifaceted abnormality of dNK cells•CTRP6 injection restores dNK cell abnormality and alleviates fetal loss

Abundant C1qtnf6 expression is distinctive for hemochorial placentae

Impaired placental-secretion of CTRP6 causes partial embryo lethality

C1qtnf6-deficiency leads to multifaceted abnormality of dNK cells

CTRP6 injection restores dNK cell abnormality and alleviates fetal loss

Biological sciences; molecular biology