Autophagy and Cathepsin D mediated apoptosis contributing to ovarian follicular atresia in the Nile tilapia

Abstract

Follicular atresia is a hormonally controlled degenerative process involving apoptosis of the somatic and germ cells. Since different signaling pathways can induce cell death, the aim of the present study was to investigate cell death signaling and crosstalk between autophagic, apoptotic, and lysosomal proteins during follicular atresia in Nile tilapia. For this, females were kept in controlled conditions for 21 days, and ovary samples were collected weekly. The atretic follicles (AF) were analyzed in three regression phases: Early, advanced, and late. Under electron microscopy, the follicular cells exhibited numerous protein synthesis organelles in the early AF. Immunoreactivity for Bcl2, Beclin1, Lc3, and Cathepsin D increased significantly in advanced AF (p < .001), when follicular cells were in intense yolk phagocytosis. In this phase, autophagosomes and autolysosomes were frequently observed. In the late AF, follicular cells had a markedly electron‐lucid cytoplasm and immunoreactivity for Bax and TUNEL assay indicated an elevated apoptosis rate. Colocalisation of Lamp1/Cathepsin D and Lc3/Caspase‐3 suggests dynamic crosstalk between the autophagy, apoptosis, and lysosome pathways. Taken together, the data indicate that autophagy plays a role in the homeostasis and clearance of the follicular cells preceding Cathepsin D mediated apoptosis during follicular atresia in Nile tilapia.

A Comparison of Reproductive Performances in Young and Old Females: A Case Study on the Atlantic Bluefin Tuna in the Mediterranean Sea

“…Both the Active-old and Active-young groups were reproductively active, with similar histological features except for levels of follicular atresia which in general remained around or below 50%, a result supported also by casp3 mRNA levels. Although levels of the other marker of cell death, becn1 , were homogeneous among groups, the higher variability observed in the group Active-young might be related to enhanced autophagy, which, upon oocyte failure to recover the required energy, represent the first step of follicular atresia preceding apoptosis along the sequential events that lead to yolk resorption and clearance of follicular cells [ 76 , 77 ]. Between the groups Active-old and Active-young, the former was identified as the most reproductively advanced according to the expression profiles of several molecular markers.…”

Autophagy in the Neuronal Ceroid Lipofuscinoses (Batten Disease)

“…In H. armigera , macroautophagy triggers CTSD maturation to promote apoptosis ( Di et al, 2021 ). Ctsd has also been linked to autophagy during ovarian follicular atresia in Nile tilapia ( Sales et al, 2019 ). In SH-SY5Y cells carrying various mutations linked to CLN10 disease (including catalytically inactive mutations), the formation of pro-CTSD and mature CTSD is affected, resulting in lowered amounts of CTSD or no CTSD protein being produced at all ( Crabtree et al, 2014 ; Bunk et al, 2021 ).…”

Role of autophagy in follicular development and maintenance of primordial follicular pool in the ovary

“…Autophagy is an intracellular, lysosomal-dependent self-degradation process that causes disassembly of damaged cell components and is phylogenetically conserved from yeast to mammals (LeopardoLeonardo et al, 2020;Meng et al, 2018;Sales et al, 2019;Xia et al, 2019;Zhou et al, 2019). It is a caspase-3 and caspase-9 independent metabolic process that does not result in DNA fragmentation and acts as a cytoprotective pathway (Duerrschmidt et al, 2006;Gioacchini et al, 2013;Z.…”

“…It is well established that apoptosis‐caspase dependent programmed cell death is the dominant cause of germ cell death during follicular atresia (Bhardwaj et al, 2018; L. Ma et al, 2019; Santos et al, 2008); however, increasing evidence demonstrates that autophagy also plays an essential role in follicular atresia (Levine & Klionsky, 2004; Levine & Kroemer, 2008). Autophagy is a lysosomal dependent self‐degradation process, for disassembly of damaged cell components and recycling of bioenergetics molecules (Leopardo et al, 2020; Meng et al, 2018; Sales et al, 2019; Watanabe & Kimura, 2018; Xia et al, 2019; Yadav et al, 2018; Zhou et al, 2019). Due to its primary functions of elimination, salvage, repair, cell differentiation, development, stress adaptation, and protection from nutrient starvation; autophagy acts as a cell survival mechanism (Gannon et al, 2012, 2013; Leopardo et al, 2020; Pajokh et al, 2019; Quan et al, 2016; Z. Tang et al, 2020; Zheng et al, 2019).…”