Simulated microgravity reduces quality of ovarian follicles and oocytes by disrupting communications of follicle cells

Abstract

Ovarian follicles are the fundamental structures that support oocyte development, and communications between oocytes and follicle somatic cells are crucial for oogenesis. However, it is unknown that whether exposure to microgravity influences cellular communications and ovarian follicle development, which might be harmful for female fertility. By 3D culturing of ovarian follicles under simulated microgravity (SMG) conditions in a rotating cell culture system, we found that SMG treatment did not affect the survival or general growth of follicles but decreased the quality of cultured follicles released oocytes. Ultrastructure detections by high-resolution imaging showed that the development of cellular communicating structures, including granulosa cell transzonal projections and oocyte microvilli, were markedly disrupted. These abnormalities caused chaotic polarity of granulosa cells (GCs) and a decrease in oocyte-secreted factors, such as Growth Differentiation Factor 9 (GDF9), which led to decreased quality of oocytes in these follicles. Therefore, the quality of oocytes was dramatically improved by the supplementations of GDF9 and NADPH-oxidase inhibitor apocynin. Together, our results suggest that exposure to simulated microgravity impairs the ultrastructure of ovarian follicles. Such impairment may affect female fertility in space environment.

Effects of Simulated Microgravity In Vitro on Human Metaphase II Oocytes: An Electron Microscopy-Based Study

“…The study aimed to investigate the effects of simulated microgravity on the ultrastructure of human MII oocytes. In fact, despite the important effects induced by the absence of gravity on human systems, organs, tissues, and the human female reproductive system in particular [22,23], only a few reports have been published about mammalian female gametes in weightlessness conditions [16,24,25]. Zhang et al (2016) [16] evidenced that simulated microgravity affects the in vitro development of mouse preantral follicles.…”

“…Wu et al (2011) [24] demonstrated that the simulated microgravity inhibits mouse oocyte maturation via altering spindle organization and inducing cytoplasmic blebbing. Chen et al ( 2023) [25] reported that simulated microgravity reduces the quality of mouse ovarian follicles and oocytes by disrupting oocyte-follicle cell intercellular contacts.…”

Long-term space missions’ effects on the human organism: what we do know and what requires further research

“…Thus, the study of the chronic effects of these factors on reproduction is necessary for the progress of space technology, the increasing duration of space missions, and plans to colonize other planets such as Mars. In vitro studies with artificially induced microgravity stimulation indicate that with long-term exposure, microgravity does not affect follicular survival and growth but reduces the quality of oocytes released from cultured follicles, as measured by the number of growth factors secreted by them, such as growth differentiation factor 9 (GDF9) ( Cheng et al, 2023 ). Studies conducted on mice placed in the space station for 91 days showed that due to the exposure, the concentration of steroid dehydrogenase 3b and 17b decreased, and the sperm count was reduced by 90% compared to the control group.…”

The Oxidative Phosphorylation and Cytoskeleton Proteins of Mouse Ovaries after 96 Hours of Hindlimb Suspension

“…However, the development of ultrastructural abnormalities was noted, which the authors believed caused chaotic granulosa cell polarity and a decrease in growth differentiation factor 9 (GDF9), which is secreted by oocytes, resulting in decreased oocyte quality in these follicles. Moreover, higher levels of reactive oxygen species were found in oocytes isolated from follicles that were cultured under simulated microgravity conditions [8].…”

“…In addition, given that mitochondrial activity depends on the structure of the cytoskeleton [15][16][17][18], changes to which can lead to the formation of the structural and functional pattern of cells under microgravity conditions, we assessed the cytoskeletal protein content and its mRNA. Oocyte quality was assessed using GDF9 mRNA content as a marker [8].…”