Early Pregnancy Events (Implantation, Decidualization, and Placentation)

Regulated cellular changes occur in the uterus during early pregnancy to facilitate the development of embryos.

Using genetically modified mouse models and uterine cell lines in vitro, the Dey and Sun labs investigate signaling pathways critical to establish a receptive uterine environment to accommodate implanting embryos and facilitate normal placentation.

Three-dimensional (3D) visualization of the whole uterus during early pregnancy helps us to reveal the fetal-maternal interaction in an unprecedented way. Using established normal and engineered trophoblast stem cells, we study molecular mechanisms that underlie processes ranging from trophoblast differentiation to invasion. These models are utilized to better understand human pregnancy.

Immune Cells in Reproduction and Organogenesis

Immune cells are traditionally known for their roles in fighting disease, but a growing body of evidence supports the emerging idea that immune cells play instructive roles during organ development and homeostasis.

Clinical observations in humans have revealed an association between infertility and disruptions in immune cells within the gonad, but the functional roles of immune cells in promoting gonad function are unclear.

Research from the De Falco lab has shown that macrophages, a specific immune cell type observed ubiquitously within organs of the body, play multiple roles during the formation of the reproductive system. Using genetically engineered mouse models to track immune cells and to ablate them during fetal and adult life, we have shown that macrophages are required for proper formation of the early fetal testis and are required for proper production of sperm in adulthood. These findings highlight important links between the immune system and reproductive health on multiple levels.

The Role of Vasculature in Stem Cell Niches

Blood vessels are well-known for their essential role in supplying oxygen and nutrients to developing organs and sustaining organ function throughout life.

However, recent studies from multiple fields have demonstrated that blood vessels, even prior to the onset of blood flow, provide important developmental signals to promote cell differentiation and organ formation in the embryo.

Work from the De Falco lab has shown that blood vessels and their associated cell types, such as pericytes and perivascular cells, play several critical roles in gonadal development. Using mouse models and organ culture methods to track blood vessels and to disrupt their growth to test their functions in organ formation, we have demonstrated that blood vessels are required for generating proper structure of the fetal testis and for establishing a niche for stem cells in the developing testis and ovary.

Furthermore, we have shown that perivascular cells, which are cells that are specifically maintained next to blood vessels, have the potential to give rise to multiple cell types in the gonad, including cells that produce important sex steroid hormones that support fertility. This research has revealed many unexpected, but critical, roles for blood vessels in gonad differentiation and function.

Cannabinoids in Reproduction

Marijuana is one of the world's most popular recreational drugs, and most commonly abused illicit drug in pregnant women in Western societies.

In recent years, the recreational use of synthetic cannabinoids is rapidly increasing. The effects of maternal use of synthetic cannabinoids during pregnancy are ambiguous due to limited studies in humans and a relative short history of the drugs.

Research from the Dey and Sun labs suggests that abnormal endocannabinoid signaling has adverse effects on multiple pregnancy events. We identified the uterus as a major target for endocannabinoid signaling. We showed that oviductal embryo transport, implantation, and placentation are compromised under abnormal endocannabinoid signaling.

Using mouse models with either elevated or silenced endocannabinoid signaling, we investigate the mechanisms of how abnormal endocannabinoids compromise pregnancy outcomes.

Clinical Translation