In C. elegans approximately half of all developing oocytes die by apoptosis during the late pachytene stage of meiosis. This physiological germline cell death is triggered by an unknown regulatory pathway that is distinct from mechanisms that induce cell death in somatic cells, or in response to genotoxic stress. Evidence suggests that these apoptotic oocytes normally donate their cytoplasm to the survivors, and thereby may function as nurse cells. We have determined that in C. elegans,
cgh-1is required to prevent essentially all developing oocytes from undergoing apoptosis through the physiological mechanism (Navarro, et al., Development 128, 3221-32, 2001). CGH-1 is a predicted DEAD box RNA helicase that is associated with germline and early embryonic P granules, and is also present in additional granules in the gonad core that persist in the early embryo in a pattern that parallels maternal mRNA. Consistent with our findings, evidence indicates that in Drosophila and Xenopus, CGH-1 orthologs associate with maternal mRNA. When germline apoptosis is prevented,
cgh-1(RNAi)oocytes develop normally in many respects but cannot be fertilized, indicating that
cgh-1 is required for oocyte function. We have hypothesized that in
cgh-1(RNAi) oocytes, the physiological germline apoptosis mechanism is triggered by a specific abnormality in oocyte or maternal gene regulation, and not by a generalized abnormality in P granule function or a non-specific impairment of oogenesis. To test this model further, we have investigated whether germline cell death is also increased by defects in the constitutive P granule components PGL-1, and the GLH DEAD box helicases. We have determined that sterility associated with the
pgl-1(
bn102) mutation is not accompanied by elevated levels of germ cell death. In addition, germline cell death is almost undetectable in sterile
glh-1;
glh-4(RNAi) hermaphrodites. The latter finding is intriguing because CGH-1 protein levels are very low or undetectable in a significant proportion of these animals. It is possible that the low levels of CGH-1 protein remaining in
glh-1;
glh-4(RNAi) hermaphrodites is sufficient to prevent excessive germ cell death, but the sharply reduced level of overall germ cell death observed suggests that it is more likely that most
glh-1;
glh-4(RNAi) germ cells do not mature to the stage at which apoptosis normally occurs. Further supporting the model that physiological germ cell death is not triggered non-specifically by defective oogenesis, germ cell apoptosis is not elevated in
gld-2(
q497) animals, in which gametogenesis is highly abnormal. CGH-1 protein levels accumulate dramatically as developing oocytes enter meiosis and the central gonad core is formed. We have tested whether this increase in CGH-1 expression is specifically dependent upon mechanisms that direct entry into meiosis. In
gld-1 (
q485) mutants, developing meiotic germ cells reenter mitosis and form a tumorous gonad. We have observed that while CGH-1 protein initially accumulates appropriately in
gld-1 (
q485) mutants, in the tumorous portion of their gonads CGH-1 levels are barely detectable. In
gld-1 (
q485);
gld-2 (
q497) double mutants, in which germline cells fail to enter meiosis, CGH-1 expression is consistently low throughout the gonad, as is characteristic of normal mitotic germ cells. These findings are consistent with the model that the increase in CGH-1 levels that normally occurs in developing oocytes is specifically associated with the process of meiosis. Together, our findings support the view that
cgh-1 is required during meiosis for normal function of a specific regulatory mechanism that determines whether a developing oocyte will survive or undergo apoptosis.