New perspective on the role of conceptus estrogens in conceptus development, maternal recognition, and the establishment of pregnancy in pigs.
The proposed signal for maternal recognition of pregnancy in pigs is estrogen, produced by the elongating conceptus. To understand the role of estrogen in porcine conceptus elongation and pregnancy establishment, a loss of function study was conducted by biallelically editing pig aromatase (CYP19A1) gene by using CRISPR/Cas9 technology. CYP19A1+/+ and CYP19A1-/- blastocysts were transferred into synchronized recipient gilts and the reproductive tract was collected on days 14 or 17 post-estrus. Elongated and attaching conceptuses were recovered from gilts receiving either CYP19A1+/+ or CYP19A1-/- embryos on both day 14 and 17. Conceptus estrogen production was inhibited as estrogen concentrations in the uterine luminal flush (ULF) of gilts with CYP19A1-/- conceptuses was significantly lower (P<0.01) than those with CYP19A1+/+ conceptuses on day 14 and day 17. Despite the loss of conceptus estrogen production, CYP19A1-/- conceptuses were capable of maintaining the corpora lutea (CL). However, gilts containing CYP19A1-/- embryos all aborted between days 27 and 31 of gestation. Attempts to rescue the pregnancy of CYP19A1-/- embryos with exogenous estrogen failed to maintain pregnancy. However, co-transfer of in vitro fertilized (IVF) CYP19A1+/+ and CYP19A1-/- embryos successfully maintained pregnancy. Furthermore, conceptus estrogen production is not essential for pre-implantation development, conceptus elongation, and the early maintenance of CL. However, conceptus estrogen is essential for programming endometrial function for maintenance of pregnancy beyond 25 days.