Oviductal Retention of Embryos in Female Mice Lacking Estrogen Receptor a in the Isthmus and the Uterus

Estrogen receptor a (ESR1; encoded by Esr1) is a crucial nuclear transcription factor for female reproduction and is expressed throughout the female reproductive tract. To assess the function of ESR1 in reproductive tissues without confounding effects from a potential developmental defect arising from global deletion of ESR1, we generated a mouse model in which Esr1 was specifically ablated during postnatal development. To accomplish this, a progesterone receptor Cre line (Pgr(Cre)) was bred with Esr1(f/f) mice to create conditional knockout of Esr1 in reproductive tissues (called Pgr(Cre)Esr1KO mice) beginning around 6 days after birth. In the Pgr(Cre)Esr1KO oviduct, ESR1 was most efficiently ablated in the isthmic region. We found that at 3.5 days post coitus (dpc), embryos were retrieved from the uterus in control littermates while all embryos were retained in the Pgr(Cre)Esr1KO oviduct. Additionally, serum progesterone (P-4) levels were significantly lower in Pgr(Cre)Esr1KO compared to controls at 3.5 dpc. This finding suggests that expression of ESR1 in the isthmus and normal P-4 levels allow for successful embryo transport from the oviduct to the uterus. Therefore, alterations in oviductal isthmus ESR1 signaling and circulating P-4 levels could be related to female infertility conditions such as tubal pregnancy.