Longitudinal patterns in progesterone metabolites in pregnant and non-pregnant Steller sea lions

Authors: Legacki, Erin; SATTLER, RANAE - Alaska Department Of Fish And Game; CONLEY, ALLEN - University Of California

Submitted to: General and Comparative Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/10/2022
Publication Date: N/A
Citation: N/A

Interpretive Summary: Similar to the several pinniped and a few terrestrial carnivore species, the Steller sea lion, has a reproductive cycle that includes pseudopregnancy (a state in which non-pregnant females produce progesterone for approximately as long as pregnant females). Due to this, serum progesterone, a steroid hormone used to detect pregnancy, cannot be used to differentiate early pregnant and non-pregnant Steller sea lions. With the use of liquid chromatography tandem mass spectrometry (LC-MS/MS), additional steroid hormones are measurable which provide more information on steroid hormone changes throughout pregnancy. Our objectives were to further characterize steroid hormone patterns in female Steller sea lion pregnancy by 1) quantifying longitudinal profiles of multiple steroid hormones in pregnant and non-pregnant females, and 2) evaluate hormone profiles to identify pregnant animals within the early stage of gestation. Three gestation stages were defined as: EARLY (August– November), MID (December-February), and LATE (March to May). Five steroid hormones, Progesterone (P4), 5a-dihydroprogesterone (DHP), 17aOH-progesterone (17OHP), 20aOH progesterone (20OHP), and androstenedione (A4), were detected in both pregnant and non-pregnant animals. A significant difference in P4 concentrations was measured between EARLY and MID gestation (p = 0.01) in both pregnant and non-pregnant animals. During MID gestation there was a significant difference (p = 0.05) between pregnant and non-pregnant animals in all pregnanes measured. Significant patterns of correlation between P4 and 17OHP and between P4 and DHP were detected during EARLY and MID gestation in non-pregnant animals. This suggests that all of those compounds were produced in the same tissue, specifically from the ovary. However, those significant correlations don’t exist in EARLY pregnant animals, which suggests a potential shift in progesterone metabolism from ovarian to alternative tissue (e.g. fetal gonads or adrenal glands) in the EARLY gestation of Steller sea lions. We were unable to identify a single steroid hormone biomarker capable of differentiating pseudopregnancy from pregnant animals and conclude that such a biomarker likely falls outside of the traditional progesterone metabolic pathway.

Technical Abstract: Similar to the several pinniped and a few terrestrial carnivore species, the Steller sea lion, has a seasonal synchronized mating schemes enabled by a female reproductive cycle that includes embryonic diapause, delayed implantation, and pseudopregnancy (a state in which the corpus luteum produces progesterone for approximately as long as in pregnant females). Due to this, circulating systemic progesterone concentrations cannot be used to differentiate pregnant and nonpregnant females during early gestation. With the use of advanced measurement technologies such as liquid chromatography tandem mass spectrometry (LC-MS/MS) additional steroid hormones are measurable which can provide additional information on the endocrine pathways throughout gestation. Our objectives were to further characterize endocrine patterns in female Steller sea lion pregnancy by 1) quantifying longitudinal profiles of hormone metabolites in pregnant and non-pregnant female sera, and 2) evaluating hormone profiles to identify pregnant animals within the early stage of gestation. Three gestation stages were delineated based on what is believed to be the period of implantation (September-October): EARLY (August– November), MID (December-February), and LATE (March to May). Five steroids, Progesterone (P 4 ), 5a-dihydroprogesterone (DHP), 17aOH-progesterone (17OHP), 20aOH-progesterone (20OHP), and androstenedione (A 4 ), were detected in both pregnant and non-pregnant animals. A significant difference in P 4 concentrations was measured between EARLY and MID gestation (p = 0.01) in both pregnant and non-pregnant animals. During MID gestation there was a significant difference (p = 0.05) between pregnant and non-pregnant animals in all pregnanes measured. Significant patterns of correlation between P 4 and 17OHP and between P 4 and DHP were detected during EARLY and MID gestation in non-pregnant animals. While those significant correlations also exist in EARLY pregnant animals, this pattern was lost by MID gestation. This loss of correlation suggests a potential shift in progesterone metabolism from ovarian to alternative tissue (e.g. fetal gonads or adrenal glands) by MID gestation in Steller sea lions. We were unable to identifying a steroid hormone biomarker capable of differentiating pseudopregnancy from pregnant animals and conclude that such a biomarker likely falls outside of the traditional progesterone metabolic pathway.