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Date of Award
Reproductive disorders and infertility affect close to 80 million people worldwide with no immediate cure in sight. Multiple studies have implicated environmental factors, such as temperature, photoperiodism, and toxic environmental contaminants, which alter our reproductive capabilities. However, the mechanisms through which our surroundings influence our reproduction remain unclear. The molecular dissection of these reproductive mechanisms is exceptionally challenging to conduct in humans. However, with its cell biology and genetic tool kits, the worm C. elegans provides a more tractable model to study the effects of the environment on reproduction.
I have focused on how food quality influences different aspects of C. elegans reproductive physiology, which shares many similarities with that of humans. For the worm, its bacterial food source is also a major source of its environmental cues. Because the sensory system acts at the interface of the environment and animal physiology, I have hypothesized that the sensory system will play an important role in many aspects of reproduction, including germline development and physiology. The study of the sensory influence on the germline could yield novel therapies against reproductive diseases and infertility.
For my thesis, I have identified specific sensory neurons that modulate distinct stages of C. elegans oocyte development in response to food quality. The taste neuron ASJ promotes early oogenesis onset on certain food sources, like E. coli CS180, by expressing a specific insulin-like peptide (ILP) known as INS-6. In contrast, the olfactory neuron AWA promotes faster oocyte maturation on these same food sources, but in an insulin-independent manner. Since I have also shown that oocyte maturation depends on the synthesis of the monounsaturated fatty acid (MUFA) palmitoleic acid, it is possible that the AWA-dependent effect on oocyte maturation involves this MUFA activity.
Although insulin signaling does not mediate the AWA effect, insulin signaling does play two roles in oocyte maturation: one that is food type-dependent during the early phases and another that is food type-independent at the later phases. The early phases of oocyte maturation require the intestinal expression of the ILP INS-1, whereas the later phases entail other ILPs. Thus, discrete aspects of C. elegans oogenesis depend on distinct sensory cues that are potentially encoded and integrated by specific ILP and non-ILP signals.
I have also shown that food quality influences other features of C. elegans reproduction, such as germline proliferation, spermatogenesis and egg laying. The food source E. coli CS180 inhibits germline proliferation, but promotes faster spermatogenesis, like oogenesis. This suggests that this particular food source favors germ cell differentiation over germ cell proliferation. Future work will address (i) the nature of the CS180-derived cues that promote germ cell differentiation and (ii) whether the same or different sensory neurons or ILPs also influence these other aspects of C. elegans physiology.
Together, my thesis work shows that successful reproduction depends on different sensory neurons and non-neuronal tissues that sense and integrate complex environmental cues through the activities of distinct signaling mechanisms.
Mishra, Shashwat, "Food Quality-Dependent Modulation Of Caenorhabditis Elegans Reproductive Physiology" (2020). Wayne State University Dissertations. 2418.