Abstract
Graphical abstractA mouse model to study uterine specific contributions to pregnancy.Maternal environmental exposures can exert impacts on the ability of the uterus to sustain healthy pregnancy. To establish an in vivo model to study this, we designed an ovariectomized mouse embryo transfer model. The rationale being future studies could expose recipient female mice to variables such as altered diet, drug, temperature, air, or activity exposure among others to define their impacts on the uterine contribution to pregnancy. Ovariectomy ensures the extent of the variable is limited to exploring outcomes on uterine but not ovarian function. Embryo transfer from healthy, unexposed donor mice guarantees that any impacts of the variable are attributed to the maternal uterine but not the embryonic state. Pregnancy outcomes including pregnancy success (number of implantation sites) and viability (number of viable vs resorbing implantation sites) can be investigated. Numerous functional outcomes can be assessed, including developmental competence encompassing decidual, placental, fetal, and vascular morphology and/or function (e.g. measured using Doppler ultrasound, comparisons of fetal growth, or molecular or histological characterization of the decidua, placenta, and fetal tissues). Lay summaryMany pregnancy complications occur because of problems in the womb (uterus), specifically the womb lining. There is a close relationship between the hormone function of the ovaries and the uterus and distinguishing between the way they both impact pregnancy success is difficult in existing studies using animals. Here, we developed a new animal model to utilize in addressing these gaps in our understanding of pregnancy.
Highlights
Assisted reproductive technologies have rapidly changed the landscape of family planning
Human in vitro culture models of endometrial receptivity and early implantation processes, including decidualization (Fitzgerald et al 2019, 2021), do not allow for the complete recapitulation of the dynamic processes involved in pregnancy establishment
For the maternal environment to be optimally prepared for pregnancy, the endometrium must be receptive to a viable embryo (Evans et al 2016)
Summary
Assisted reproductive technologies have rapidly changed the landscape of family planning. Clinical pregnancy rates following in vitro fertilization or intracytoplasmic sperm injection have stagnated in recent years (Norwitz et al 2001, Kupka et al 2014, Ledee et al 2016), indicating many morphologically good-quality embryos fail to implant and establish a pregnancy. This suggests other barriers, including uterine deficiencies, contribute to the limited pregnancy success rates observed clinically (Richter et al 2006, Ruiz-Alonso et al 2013, 2014, Coughlan et al 2014). The field still lacks an understanding of the uterine drivers of implantation failure and early pregnancy loss and the development of pregnancy complications that manifest after successful implantation
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