Pre-implantation mouse embryo movement under hormonally altered conditions

Pre-implantation embryo movement is crucial to pregnancy success, but the role of ovarian hormones in modulating embryo movement is not understood. We ascertain the effects of altered hormonal environment on embryo location using two delayed implantation mouse models: natural lactational diapause (ND); and artificially induced diapause (AD), a laboratory version of ND generated by ovary removal and provision of supplemental progesterone (P4). Previously, we showed that embryos in a natural pregnancy (NP) first display unidirectional clustered movement, followed by bidirectional scattering and spacing movement. In the ND model, we discovered that embryos are present as clusters near the oviductal-uterine junction for ∼24 h longer than NP, followed by locations consistent with a unidirectional scattering and spacing movement. Intriguingly, the AD model resembles embryo location in NP and not ND. When measuring serum hormone levels, unlike the popular paradigm of reduced estrogen (E2) levels in diapause, we observed that E2 levels are comparable across NP, ND and AD. P4 levels are reduced in ND and highly increased in AD when compared to NP. Further, exogenous administration of E2 or P4 modifies embryo location during the unidirectional phase, while E2 treatment also affects embryo location in the bidirectional phase. Taken together, our data suggest that embryo movement can be modulated by both P4 and E2. Understanding natural hormonal adaptation in diapause provides an opportunity to determine key players that regulate embryo location, thus impacting implantation success. This knowledge can be leveraged to understand pregnancy survival and implantation success in hormonally altered conditions in the clinic.