Insights Into the Hypometabolic Stage Caused by Prolonged Starvation in L4-Adult Caenorhabditis elegans Hermaphrodites.

Animals alter their reproductive cycles in response to changing nutritional conditions, to ensure that offspring production only occurs under favorable circumstances. These adaptive strategies include reversible hypometabolic states of dormancy such as "arrest" and "diapause." The free-living nematode Caenorhabditis elegans can arrest its life cycle during some larval stages without modifying its anatomy and physiology until conditions improve but it can also modify its morphological and physiological features to cope with harsh conditions and transition into diapause. The well-defined "dauer" diapause was described more than 40 years ago and has been the subject of comprehensive investigations. The existence of another hypometabolic state, termed adult reproductive diapause (ARD), has been debated after it was first described 10 years ago. Here, we review the current knowledge regarding the effect of food deprivation during the pre-reproductive larval and adult stages on overall organismal homeostasis, highlighting the implications on germ cell maintenance and fertility preservation.

Apoptosis contributes to protect germ cells from the oogenic germline starvation response but is not essential for the gonad shrinking or recovery observed during adult reproductive diapause in C. elegans.

When C. elegans hermaphrodites are deprived of food during the mid-L4 larval stage and throughout adulthood, they enter an alternative stage termed "adult reproductive diapause (ARD)" in which they halt reproduction and extend their lifespan. During ARD, germ cell proliferation stops; oogenesis is slowed; and the gonad shrinks progressively, which has been described as the "oogenic germline starvation response". Upon refeeding, the shrunken gonad is regenerated, and animals recover fertility and live out their remaining lifespan. Little is known about the effects of ARD on oocyte quality after ARD. Thus, the aim of this study was to determine how oocyte quality is affected after ARD by measuring brood size and embryonic lethality as a reflection of defective oocyte production. We found that ARD affects reproductive capacity. The oogenic germline starvation response protects oogenic germ cells by slowing oogenesis to prevent prolonged arrest in diakinesis. In contrast to a previous report, we found that germ cell apoptosis is not the cause of gonad shrinkage; instead, we propose that ovulation contributes to gonad shrinkage during the oogenic germline starvation response. We show that germ cell apoptosis increases and continues during ARD via lin-35/Rb and an unknown mechanism. Although apoptosis contributes to maintain germ cell quality during ARD, we demonstrated that apoptosis is not essential to preserve animal fertility. Finally, we show that IIS signaling inactivation partially participates in the oogenic germline starvation response.