Bovine Animal Model for Studying the Maternal Microbiome, in utero Microbial Colonization and Their Role in Offspring Development and Fetal Programming

Abstract

Recent developments call for further research on the timing and mechanisms involved in the initial colonization of the fetal/infant gut by the maternal microbiome and its role in Developmental Origins of Health and Disease (DOHaD). Although progress has been made using primarily preterm infants, ethical and legal constraints hinder research progress in embryo/fetal-related research and understanding the developmental and mechanistic roles of the maternal microbiome in fetal microbial imprinting and its long-term role in early-life microbiome development. Rodent models have proven very good for studying the role of the maternal microbiome in fetal programming. However, some inherent limitations in these animal models make it challenging to study perinatal microbial colonization from a biomedical standpoint. In this review, we discuss the potential use of bovine animals as a biomedical model to study the maternal microbiome, in utero microbial colonization of the fetal gut, and their impact on offspring development and DOHaD.

Keywords: biomedical research; bovine model; developmental origins of health and disease; fetal programming; in utero microbial colonization; maternal microbiome.

Figure 1

Schematic overview of the bovine reproductive tract, different developmental stages of utero-placenta and fetal development (A, day 25–30 after mating; B, mid to late pregnancy), and the timeline of placental and embryonic/fetal development during the entire pregnancy in cattle (C). Timeline modified from Caton et al. (2020). As shown in (A) and (B), the fetus and placenta (both the maternal and fetal portions) are contained in the gravid uterine horn (normally present in only one uterine horn as cattle typically have singleton pregnancies). Over the course of pregnancy, from early (A) to mid to late (B) pregnancy, the fetus develops (organogenesis is completed by about day 45–50 of pregnancy), and the fetal organs and placenta grow and mature. As mentioned, the placenta consists of both fetal (cotyledon and intercotyledonary fetal membranes) and maternal (caruncle and intercaruncular endometrium) components.

Figure 2

Schematic overview of bovine reproductive tract, and images of utero-placental development from 35 to 85 days after mating as well as fetuses obtained during early (day 35) to late (day180) gestation. Length of gestation is around 280 days. In the upper images, the uterine horns have been opened to reveal the utero-placental surfaces. In the lower images, the uterus has been opened to reveal the fetus in its fetal membranes (chorioallantois and amnion; day 35) or the fetuses have been removed to illustrate their continued growth and development.

Figure 3

Overall summary of the microbial communities residing within the respiratory, gastrointestinal, and reproductive tracts of cattle. The pie chart represents the most relatively abundant bacterial phyla. The relative abundance of these phyla present in pie charts was adapted from McMullen et al. (2020a) (respiratory tract), Mao et al. (2015), and Holman and Gzyl (2019) (gastrointestinal tract), reproductive tract (Amat et al., 2021b; vagina; Wang et al., 2018; Cervix; Quereda et al., 2020; Uterine).