An air-liquid interphase approach for modeling the early embryo-maternal contact zone

Abstract

We developed an air-liquid interphase culture procedure for mammalian oviduct epithelial cells leading to the formation of functional epithelial tissues, which generate oviduct fluid surrogates. These in vitro oviduct epithelia can be co-cultured with living zygotes and enable embryonic development up to the blastocyst stage without addition of embryo culture medium. The described strategy is broadly applicable to analyze early embryo-maternal interactions under standardized in vitro conditions.

Air‐liquid interface cell culture: From airway epithelium to the female reproductive tract

“…Air‐liquid interface models allow acquisition and analysis of both the apical/luminal fluid created by the epithelia and the conditioned basolateral medium. It has been shown that ALI‐derived oviductal fluid surrogates share apparent similarities to oviductal fluid in vivo (Chen et al., ; Simintiras et al., ). As estrous cycle dependent changes in the epithelium can be mimicked by application of progesterone and estradiol to the basal compartment (Chen et al., 2013a, ), they can also be employed to investigate the dynamic, steroid‐driven modifications in the fluid composition during the peri‐conceptional period.…”

“…Air‐liquid interface‐based in vitro models of FRT epithelia can be used to culture living zygotes (Chen et al., ; Ferraz, Henning, Costa, et al., ; Ferraz et al., ). Murine, porcine, as well as bovine zygotes grown within the apical compartment of oviduct ALI systems developed up to the blastocyst stage without any addition of embryo culture medium (Chen et al., ). First results showed that the marker gene expression of bovine embryos cultured on ALI oviduct epithelia is not largely different from that of embryos produced via standard in vitro procedures.…”

“…The culture system consists of an apical and a basal compartment, which are separated by a porous filter support and the confluent epithelial tissue. Upon differentiation, epithelial cells of mucociliary phenotype secrete mucus fluid into the apical compartment TA B L E 1 Examples for cell culture models of female reproductive tract epithelia using the air-liquid interface (ALI) approach Chen et al (2013aChen et al ( ,b, 2015Chen et al ( , 2018Chen et al ( , 2017 and Miessen, Sharbati, Einspanier, and Schoen (2011) Cattle Morphology, TEER, apical fluid proteome, fertilization, embryo development, embryonic marker gene expression after co-culture Chen et al (2017), Ferraz et al (2017a) and Gualtieri et al (2012Gualtieri et al ( , 2013 Mouse Morphology, TEER, apical fluid proteome, embryo development Chen et al (2017) Abbreviation: TEER, transepithelial electrical resistance.…”

“…Air-liquid interface cultures have also been introduced to study the early embryonic microenvironment and interactions between the FRT epithelia and gametes or the early embryo (Chen, Einspanier, & Schoen, 2013a;Chen et al, 2017;Ferraz et al, 2018). As epithelia are functionally defined by their baso-apical polarity, a luminal and basolateral secretome of FRT epithelia can be distinguished.…”

Understanding the uterine environment in early pregnancy in cattle: How have the omics en-hanced our knowledge?

“…Owing to the technical, and often ethical, limitations surrounding in vivo sampling, one direction towards addressing this includes in vitro modelling. Advances have been made regarding the production of bovine in vitro derived oviduct fluid (ivDOF) which resemble in vivo derived fluid and moreover supports early embryo development (Chen et al, 2017), however, this can be considered currently under optimisation and has yet to be recapitulated to the uterus. The delay in an in vitro uterine luminal fluid (ivULF) is partly attributable to the increased complexity of the endometrium, notably the presence of glands and a greater number of different cell types.…”