(297) Elevated Basal and Oxytocin-induced Prostaglandin F2α (PGF) on Days 30 and 50 of Pregnancy is due to Upregulation of Uterine PGF Synthesis Machinery in Beef Cows

Ellie G. Kidwell¹; Calista G. Hubbard¹; Florentino P.J. da Silva Junior¹; Alexandria Crist¹; Natalia P. Folchini¹; Caleb Rykaczewski¹; Muhammad Saad¹; Jackie S. Moates¹; Madeline A. Dalton¹; Lillian X. Ehresmann¹; Alvaro Garcia-Guerra¹; Rafael R. Domingues¹

1. Department of Animal Sciences, The Ohio State University, Columbus, Ohio

 

Abstract Text:

During early pregnancy, the embryo interacts with the maternal system to prevent uterine secretion of PGF2α (PGF) to allow for CL maintenance. After day 25, basal PGF is upregulated; however, it does not cause CL regression. In experiment 1, we determined the uterine and luteal transcriptomic profile associated with greater secretion of PGF on days 30 (P30) and 50 (P50) of gestation in contrast with day 15 of the estrous cycle in nonpregnant (noninseminated) cows (NP15). In experiment 2, we investigated the endocrine, uterine and luteal responses to oxytocin-induced secretion of PGF in P30, P50, and NP15. We administered 50 IU of oxytocin intramuscularly or an equivalent volume of saline. Uterine cervical cytology and CL biopsy were collected two hours post treatment; blood samples were collected for 24 hours. Data were evaluated using generalized mixed models. In experiment 1, baseline PGF metabolite (PGFM) concentrations were greatest (P< 0.0001) in P50, intermediate in P30, and least in NP15 (48.4±3.9, 29.9±2.6, and 9.6±2.1 pg/mL, respectively). Cervical expression of estradiol receptor 1 (ESR1), progesterone receptor, oxytocin receptor (OXTR), and PGF synthase (PGFS) were greater (P< 0.05) in P50 compared to NP15. The ESR1 in P30 was greater (P=0.005) than NP15 but less (P=0.01) than P50; PGFS in P30 was decreased (P=0.03) compared to P50.  Estradiol receptor 2, an ESR1 inhibitor, was less (P< 0.001) in NP15 than P30 and P50 and tended to be less (P=0.09) in P30 compared to P50. The dynamic expression of these genes in the uterine cervix supports the elevated PGF synthesis on days 30 and 50 compared to NP15. In the CL, abundance of interferon stimulated gene 15 was greater (P=0.01) for P30 than NP15 and tended to be greater (P=0.09) compared to P50. The mRNA for prostaglandin transporter was greater (P=0.01) in P30 and P50 compared to NP15. The mRNA expression of PGF receptor was greater in P50 (P=0.02) and P30 (P=0.06) compared to NP15. In experiment 2, oxytocin treatment promoted secretion of PGF in all evaluated periods (NP15, P30, and P50). However, PGFM peak was greater (P=0.0002) in P50 than P30, which was greater than in NP15 (335.1±64.3, 162.1±45.0, and 83.2±12.6 pg/mL, respectively). The PGFM peak occurred later (P< 0.0001) in P30 (110.0±11.2 minutes) and P50 (108.8±5.5 minutes) compared to NP15 (51±9.3 minutes). Although oxytocin elicited PGF pulsatile secretion in all cows, there was no effect (P >0.1) of treatment on circulating concentrations of progesterone. In NP15 cows, oxytocin treatment tended to upregulate (P=0.09) cervical OXTR and luteal cytochrome P450, whereas luteal prostaglandin E synthase tended to decrease (P=0.07) due to treatment. Taken together, these data support our hypothesis that the greater basal secretion of PGF after day 25 of pregnancy is due to increased uterine secretion of PGF as a result of upregulation of the uterine PGF synthesis machinery. Interestingly, although oxytocin treatment promoted a PGF/PGFM pulse on days 30 and 50 of pregnancy, it did not affect circulating progesterone or CL maintenance likely due to a luteal maintenance mechanism yet to be determined.