Anabolic Steroids-Driven Regulation of Porcine Ovarian Putative Stem Cells Favors the Onset of Their Neoplastic Transformation

Abstract

Nandrolone (Ndn) and boldenone (Bdn), the synthetic testosterone analogues with strong anabolic effects, despite being recognized as potentially carcinogenic compounds, are commonly abused by athletes and bodybuilders, which includes women, worldwide. This study tested the hypothesis that different doses of Ndn and Bdn can initiate neoplastic transformation of porcine ovarian putative stem cells (poPSCs). Immunomagnetically isolated poPSCs were expanded ex vivo in the presence of Ndn or Bdn, for 7 and 14 days. Results show that pharmacological doses of both Ndn and Bdn, already after 7 days of poPSCs culture, caused a significant increase of selected, stemness-related markers of cancer cells: CD44 and CD133. Notably, Ndn also negatively affected poPSCs growth not only by suppressing their proliferation and mitochondrial respiration but also by inducing apoptosis. This observation shows, for the first time, that chronic exposure to Ndn or Bdn represents a precondition that might enhance risk of poPSCs neoplastic transformation. These studies carried out to accomplish detailed molecular characterization of the ex vivo expanded poPSCs and their potentially cancerous derivatives (PCDs) might be helpful to determine their suitability as nuclear donor cells (NDCs) for further investigations focused on cloning by somatic cell nuclear transfer (SCNT). Such investigations might also be indispensable to estimate the capabilities of nuclear genomes inherited from poPSCs and their PCDs to be epigenetically reprogrammed (dedifferentiated) in cloned pig embryos generated by SCNT. This might open up new possibilities for biomedical research aimed at more comprehensively recognizing genetic and epigenetic mechanisms underlying not only tumorigenesis but also reversal/retardation of pro-tumorigenic intracellular events.

Folate receptor‐1 is vital for developmental competence of goat embryos

“…Despite effective knockdown, 5.87% of embryos was able to develop into blastocysts, possibly due to the presence of maternally contributed FOLR1 which may eventually exhausted until blastocyst stage. Our results are in line with a previous study (Strandgaard et al, 2017), which demonstrated the compromised ability of mouse embryos to develop to blastocyst stage after TA B L E 1 Effect of FOLR1 knockdown on the rate of blastocyst production injection (Kharche et al, 2016;Magata et al, 2019;Menéndez-Blanco et al, 2020;Shirazi et al, 2018) and cloning by somatic cell nuclear transfer (Gorczyca et al, 2021;Hernández Martínez et al, 2020;Samiec et al, 2019;Skrzyszowska & Samiec, 2020Wiater et al, 2021).…”

“…The future studies at our laboratory may decipher some of these questions in order to thoroughly elucidate the importance of FOLR1 as a pivotal biomarker suitable for prediction of augmented susceptibility of embryonic genomes to efficient epigenetic reprogramming of their transcriptional activities. The latter could enable the embryologists to estimate the increased developmental competences and molecular quality of caprine and other mammalian species embryos produced by such modern assisted reproductive technologies as microsurgical IVF by intracytoplasmic sperm injection (Kharche et al., 2016; Magata et al., 2019; Menéndez‐Blanco et al., 2020; Shirazi et al., 2018) and cloning by somatic cell nuclear transfer (Gorczyca et al., 2021; Hernández Martínez et al., 2020; Samiec et al., 2019; Skrzyszowska & Samiec, 2020, 2021; Wiater et al., 2021).…”

Cellular and Molecular Nature of Fragmentation of Human Embryos

“…It is beyond any doubt that, in the near future, a wide panel of the investigations from the fields of experimental and applied embryology should have been targeted at the precisely identifying and comprehensively exploring a broad spectrum of morphological, ultrastructural, biochemical, and molecular determinants responsible for increased incidence of the processes leading to initiation and progression of embryo fragmentation. The thorough characterization of the aforementioned determinants seems to be strongly justified in order to recognize the highly predictable biomarkers related to diminishments in not only molecular quality parameters, but also the extracorporeal and peri-implantation developmental capabilities of the ex vivo produced embryos created by such modern ARTs as in vitro fertilization and intracytoplasmic sperm injection in humans and other mammalian species and somatic cell nuclear transfer (SCNT)-mediated cloning in other mammalian species [114][115][116][117][118][119].…”

Oroxin A reduces oxidative stress, apoptosis, and autophagy and improves the developmental competence of porcine embryos in vitro

“…Furthermore, for the aforementioned reasons, the desirable OA‐mediated impacts might be reflected in the enhancements of ex vivo developmental potential, molecular quality, mitochondrial functions and incidence of genomic DNA‐inherited genes to undergo reprogramming of their transcriptional activities in porcine and other mammalian in vitro‐produced embryos that have been created using a variety of advanced assisted reproductive technologies (ARTs). Among those ARTs, special importance should be assigned to in vitro fertilization (IVF) by standard gamete co‐incubation or intracytoplasmic sperm injection (Arraztoa et al, 2017; Casillas et al, 2018; Kagawa et al, 2022; Thongkittidilok et al, 2022) and cloning by somatic cell nuclear transfer (Deng et al, 2020; Gorczyca et al, 2021; Jeong et al, 2021; Wiater et al, 2021).…”