P1012 - INFLUENCE OF ADVANCED MATERNAL AGE ON MITOPHAGY KEY MARKERS IN HUMAN PLACENTA.

P1012

INFLUENCE OF ADVANCED MATERNAL AGE ON MITOPHAGY KEY MARKERS IN HUMAN PLACENTA.

J. M. Toledano^1,2,3,*, M. Puche-Juarez^1,2,3, J. J. Ochoa^1,2,3,4, J. Diaz-Castro^1,2,3,4, R. Ruiz-Sanchez¹, C. De Paco-Matallana⁵, J. Sánchez-Romero⁵, M. P. Carrillo⁶, J. Moreno-Fernandez^1,2,3,4

¹Physiology, University of Granada, ²Centro de Investigación Biomédica, ³Institute of Nutrition and Food Technology "José Mataix Verdú", ⁴Instituto de Investigación Biosanitaria (IBS), Granada, ⁵Obstetrics and gynaecology, Hospital Clínico Universitario Virgen de la Arrixaca, El Palmar, Murcia, ⁶Obstetrics and gynaecology, Virgen de las Nieves University Hospital, Granada, Spain

Rationale: Advanced maternal age (AMA), defined as ≥35 years old at delivery, has been related to adverse neonatal/obstetric outcomes and gestational complications, potentially affecting different aspects of placental function. Mitochondria play a prominent role in placental activity and have been previously linked to some of these complications, so it is reasonable to hypothesize that the function of these organelles might get affected during AMA pregnancies. Consequently, the aim of this study was to evaluate mitochondria from AMA placentas in order to find out possible changes regarding mitophagy.

Methods: Placentas from ≥35 years old women (n=26) and <35 years old women (n=26) were collected in two hospitals; “Virgen de las Nieves” (Granada) and “Virgen de la Arrixaca” (Murcia). Tissue samples were taken from the subchorial zone of the placenta. These were homogenized while protein was extracted in radioimmunoprecipitation buffer (RIPA) together with protease inhibitor mixture. Protein extracts were used to determine protein expression of mitophagy markers (PINK1, PARKIN and OPTN) by western blot, being the quantification of the signal analyzed with the ImageJ software. The statistical analysis was performed with GraphPad Prism 8.

Results: Protein expression of both PINK1 and PARKIN increased in AMA samples (P<0.05 and P<0.001, respectively) compared to those in the control group. Regarding OPTN, protein expression was decreased in AMA samples (P<0.01) in comparison with the control group.

Conclusion: AMA seems to induce functional changes in placental mitochondrial dynamics, affecting mitophagy. There seems to be an increase in the activity of the PINK1/PARKIN axis, even though the main autophagy receptors further involved may be different from OPTN. All this might be associated with an excess of dysfunctional organelles which need to be removed from the mitochondrial pool.

Disclosure of Interest: None declared