Microphysiologic systems in female reproductive biology

Abstract

Microphysiologic systems (MPS), including new organ-on-a-chip technologies, recapitulate tissue microenvironments by employing specially designed tissue or cell culturing techniques and microfluidic flow. Such systems are designed to incorporate physiologic factors that conventional 2D or even 3D systems cannot, such as the multicellular dynamics of a tissue-tissue interface or physical forces like fluid sheer stress. The female reproductive system is a series of interconnected organs that are necessary to produce eggs, support embryo development and female health, and impact the functioning of non-reproductive tissues throughout the body. Despite its importance, the human reproductive tract has received less attention than other organ systems, such as the liver and kidney, in terms of modeling with MPS. In this review, we discuss current gaps in the field and areas for technological advancement through the application of MPS. We explore current MPS research in female reproductive biology, including fertilization, pregnancy, and female reproductive tract diseases, with a focus on their clinical applications. Impact statement This review discusses existing microphysiologic systems technology that may be applied to study of the female reproductive tract, and those currently in development to specifically investigate gametes, fertilization, embryo development, pregnancy, and diseases of the female reproductive tract. We focus on the clinical applicability of these new technologies in fields such as assisted reproductive technologies, drug testing, disease diagnostics, and personalized medicine.

Mechanisms of Key Innate Immune Cells in Early- and Late-Onset Preeclampsia

“…Physiological changes occur in nearly all organs during pregnancy and the pharmacokinetics and pharmacodynamics of drugs are often significantly altered, although the specific changes are mostly undetermined (212). New micro-physiological systems technology such as "Organ on a chip" models may in the future be used to help fill these gaps in knowledge (213). Dysregulation of TLRs and detection of host-derived DAMPs contribute to the pathogenesis of preeclampsia, as described above (214).…”

Pathways coordinating oocyte attrition and abundance during mammalian ovarian reserve establishment

“…Historically, studies have been complicated by inaccessibility of the organ of interest (fetal ovary), limited sample inputs, and limited ability to faithfully maintain the necessary systems in vitro. In the last decade, however, new technologies have been developed to maintain ovaries in long‐term, 3D culture (Laronda et al, 2017); to utilize microfluidics, or “ovary‐on‐a‐chip,” systems to mimic the physiological environment of a developing ovary (Aziz et al, 2017; A. N. Young, Moyle‐Heyrman, Kim, & Burdette, 2017); and to differentiate gametes in vitro from induced stem cell progenitors (Hikabe et al, 2016; Miyauchi, Ohta, & Saitou, 2018). All of these techniques have allowed for better manipulation of a challenging system, and greater statistical power of results.…”

Organoid technology in female reproductive biomedicine

“…The main reason for this high rate of failure is related to the lack of reliable disease and relevant human models, and inaccurate results from animal models [55][56][57]. The developmental and reproductive toxicity of a vast majority of about 75, 000-85,000 chemical substances in commerce has not been investigated [1]. Despite public concerns regarding the reproductive toxicity of chemicals, the field of reproductive toxicology (repro-toxicology) is in its infancy; therefore, more well-targeted research in this field is needed to better understand and prevent reproductive health risks.…”

“…The female reproductive system is of utmost importance to a woman's quality of life; it produces sex hormones and oocytes, provides the site for fertilization, and supports the fetal development [1,2]. Diseases and disorders of the female reproductive system are not adequately studied, especially in the areas of endometriosis, gynecological cancers, sexually transmitted diseases (STDs), and pregnancy disorders (including intrauterine growth restriction, miscarriage, and recurrent miscarriage), in addition to medications that have deleterious effects on the reproductive system [2][3][4][5].…”