New perspective on the role of conceptus estrogens in conceptus development, maternal recognition, and the establishment of pregnancy in pigs.

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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[less than]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.

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