Sex is a fundamental biological variable that shapes tissue physiology, disease susceptibility, and therapeutic responses, yet female-specific biology and dynamic hormonal states remain underrepresented in preclinical research. This is particularly relevant to reproduction, where cyclical estrogen and progesterone fluctuations continuously reshape the structure and function of the female reproductive tract (FRT).

Human organoids and microfluidic Organ-on-a-Chip (Organ Chip) platforms provide opportunities to recapitulate human tissue architecture, dynamic hormonal exposure, fluid flow, and cell–cell interactions in controlled experimental systems. A central focus of our work is the bidirectional interaction between sperm and the FRT. Rather than serving as a passive conduit for sperm transport, the FRT provides an active microenvironment that regulates sperm survival, motility, transport, and function through epithelial, biochemical, hormonal, and biomechanical cues. These platforms further enable investigation of how reproductive tract tissues and their secreted factors influence sperm function and sperm–epithelium communication.

Beyond modeling individual reproductive organs, FRT Organ Chips provide opportunities to investigate how hormonal state and tissue-specific microenvironments coordinate reproductive function. These systems may provide new mechanistic insights into fertility and infertility while enabling the identification and evaluation of novel targets for contraception and reproductive therapeutics.

Together, hormone-aware and interaction-aware Organ Chips establish a human-relevant framework for studying female reproductive biology by integrating hormonal dynamics, tissue physiology, and gamete–tissue communication. Such platforms have the potential to advance predictive preclinical research and support more precise approaches to women’s reproductive health

Shiyan Tang, PhD, is a Postdoctoral Research Fellow at the Wyss Institute for Biologically Inspired Engineering at Harvard University, USA. She completed her PhD in Women’s and Reproductive Health at the University of Oxford, UK, where her research focused on fertility preservation and in vitro modeling of reproductive development. She has extensive experience in organoid culture, organ-on-a-chip technologies, reproductive biology, fertility preservation, and advanced imaging approaches.

Her current research focuses on developing human-relevant Organ Chip and organoid models of the female reproductive tract to investigate hormone-dependent tissue biology, sperm–female reproductive tract interactions, and reproductive health. Her work integrates microphysiological systems with reproductive biology to develop predictive preclinical models for fertility, contraception, and women’s health.