Heat stress enhances VLDL secretion in chicken ovarian follicles to potentiate its impact on follicular cell survival and maturation

Chicken ovaries possess the machinery of VLDL production in response to heat stress (HS). The study sought to define the role of VLDL secretion by hierarchical follicles along their development under HS. HS (42°C) for 8 hr (HS8H) or HS3H and following recovery at 37°C to 16 hr (3H13R) upregulated PCNA and/or IL-1β expressions in granulosa (GC) and theca (TH) cells and augmented progesterone (P4) and estradiol (E2) production, respectively. Inhibition of VLDL production by Lomitapide and Mipomersen suppressed P4 secretion at 3H13R and HS8H, but differentially affected E2 production, leading to altered secretion fashions under thermoneutral conditions (37°C, NC) and during post-HS recovery, suggesting interfered steroidogenic competence toward maturation. HS regardless of duration and recovery or interference with VLDL secretion under NC provoked ROS and MDA accumulation in both cell types. GCs transiently increased VLDL secretion at HS3H and showed overt cell death at 3H13R, while TH cells sustained VLDL production and retained viability. Prolonged HS over 8 hr impaired viability of both cell types with disparate responses in lipid dynamics; constantly depressed neutral lipids and cholesterol in GCs, while TH cells showed increased neutral lipids before HS8H but rapid dissipation to HS16H and suppressed cholesterol at HS8H. Surprisingly, Lomitapide and Mipomersen rescued TH cell viability at HS8H and 8H8R in association with alleviated lipid, MDA, and ROS accumulations, whereas GCs exhibited improved viability at HS8H, but not at 8H8R and 3H13R in couple with worse depletion of neutral lipids and cholesterol, suggesting that HS operates at VLDL production to alter cellular lipid dynamics to potentiate cell death, while TH cells are more thermoresistant due to a proficient adaption in lipid disposal. In conclusion, HS enhances VLDL production in hierarchical follicles to augment its impacts on follicular cell fate, but routine secretion of VLDL is obligatory to sustain follicle maturation under normal conditions, in which TH cells are highly agile in lipid remodeling and redox regulation in adaption to heat insults.