Dr. Tony DeFalco, PhD delivers the annual Danielle Maatouk Lecturship
The Center for Reproductive Science Community had the pleasure of hosting the Danielle Maatouk Memorial Lectureship with keynote speaker Tony De Falco, PhD, on April 22, 2022. Dr. De Falco is an Associate Professor of Developmental Biology and Co-Director of the Center for Reproductive Sciences at Cincinnati Children’s Hospital Medical Center. His research investigates the role of vasculature and immune cells in male and female gonadal development. The talk was titled, “Vasculature and immune cells: an unexpected toolkit for building the gonad.”
Dr. De Falco aims to investigate the processes and cell types that regulate the differentiation of the developing gonad and maintain male fertility. Specifically, he found that interstitial cells, vasculature, and macrophages play crucial roles in this process. Vasculature, for instance, is involved in the development of the spermatogonial stem cell niche, which allows stem cells to undergo continuous proliferation throughout the male reproductive life span. Compared to females, males display increased gonadal vascularization beginning 12.5 days post coitum, suggesting that vasculature may play a role in early gonadal differentiation. To supplement these observations, Dr. De Falco and his students developed an ex vivo vascular inhibition culture technique. Male testes are dissected while in utero and cultured with vascular inhibition reagents. Utilizing quantitative PCR and immunofluorescence, the group assessed gene expression and vasculature at various time points in embryonic development. Additionally, blocking vasculature results in the loss of perivascular stem/progenitor cells that differentiate to form Leydig cells, peritubular myoid cells, and pericytes, which are all important for gonadal development and function.
Dr. De Falco and his team also investigated the presence of perivascular cells in the fetal ovary. Like the male gonad, ablation of postnatal perivascular progenitor cells disrupts the formation of somatic cells in the ovary, resulting in multioocytic follicles. Interestingly, female transgenic mouse models with mutations in genes important for gonadal differentiation exhibit testis-like vascularization. Perhaps, vascular organization can lead to differences of sexual development (DSDs) or adult infertility.
Along with vasculature, macrophages are necessary for gonad morphogenesis, differentiation, and paracrine interactions between different testis cell types. Dr. De Falco and his students depleted the fetal macrophage population and found that macrophages are intimately associated with blood vessels during fetal testis development. His team reasoned those macrophages play a critical role in vascular remodeling during gonad differentiation. Overall, Dr. De Falco’s research highlights the importance of immune and vascular cells for gonadal development and sexual dimorphism. His work will aid in understanding the causes underlying DSDs and infertility.
This annual lectureship is a memorial to Dr. Danielle Maatouk, an exceptional scientist in the field of reproductive science and medicine who passed away in 2016 after a long battle with cancer. Her work investigated epigenomic regulation of gene expression and cell fate determination during fetal development. Every year, the Center for Reproductive Science invites scientists who have continued to build upon Dr. Maatouk’s research. It was a pleasure to attend this memorial lectureship and hear not only about Dr. DeFalco’s studies, but Dr. Maatouk’s legacy in the field.