Prostaglandin F2α‐induced luteolysis involves activation of Signal transducer and activator of transcription 3 and inhibition of AKT signaling in cattle

• Published in: Molecular reproduction and development Vol. 84; no. 6; pp. 486 - 494
• Main Authors: Rovani, Monique T., Ilha, Gustavo F., Gasperin, Bernardo G., Nóbrega, Jandui E., Siddappa, Dayananda, Glanzner, Werner G., Antoniazzi, Alfredo Q., Bordignon, Vilceu, Duggavathi, Raj, Gonçalves, Paulo B. D.
• Format: Journal Article
• Language: English
• Published: United States 01.06.2017
• Subjects: Animals; apoptosis; Cattle; corpus luteum; Corpus Luteum - metabolism; cow; Dinoprost - pharmacology; Female; Luteolysis - metabolism; pregnancy; progesterone; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction - drug effects; STAT3 Transcription Factor - metabolism; apoptosis; corpus luteum; cow; pregnancy; progesterone
• ISSN: 1040-452X; 1098-2795
• DOI: 10.1002/mrd.22798

Prostaglandin F2α (PGF) induces the precipitous loss of steroidogenic capabilities and cellular death in the corpus luteum of many species, yet the molecular mechanisms underlying this event are not completely understood. Signal transducer and activator of transcription 3 (STAT3) was activated in granulosa cells during follicle atresia, whereas AKT is immediately down‐regulated in the corpus luteum after PGF treatment in cattle; however, their involvement in both functional and morphological luteolysis in monovular species still need to be determined. Blood samples and corpus lutea were collected from cows before (0) and 2, 12, 24, and 48 hr after PGF treatment on Day 10 of the estrous cycle (4–5 cows per time point). Serum progesterone concentrations decreased by threefold (p < 0.05) within 2 hr, confirming functional luteolysis. The mRNA abundance of the pro‐apoptotic gene BAX increased 12–48 hr post‐PGF treatment (p < 0.05), while morphological luteolysis was observed 24 and 48 hr after PGF treatment, based on the loss of plasma membrane integrity, reduction of cytoplasmic volume, and pyknotic nuclei. Phosphorylated STAT3 increased, peaking at 12 hr, and remained elevated until 48 hr after PGF treatment. SOCS3 transcript abundance also increased (p < 0.05) starting at 2 hr post‐PGF treatment. In contrast, AKT phosphorylation decreased by 12 hr after treatment. Thus, activation of STAT3 and inactivation of AKT signaling are involved in structural regression of the corpus luteum.