**3.1 The molecular mechanisms of vitellogenesis and oogenesis**

The conversion of protein from the blood meal into YPPs for eggs biogenesis is a vital component of the reproductive cycle and understanding how this process is regulated is necessary to design safe, specific, and effective ways to block reproduction in vectors. Mosquito 20E has been shown to play multiple roles in *Anopheles.*

Apart from regulating monogamy in *Anopheles*, the male-transferred 20E was shown to be important in maintaining sperm viability over the female lifetime through induction of the heme peroxidase 15 (HPX15) [24]. Accordingly, HPX15 knockdown was shown to dramatically increase the ratio of infertile eggs. Upon insemination, the male 20E further interacts with the female Mating-Induced Stimulator of Oogenesis (MISO) and induces an increase in fecundity by increasing the expression of LP and oocyte numbers [25]. Finally, 20E was also shown to be necessary for *Anopheles* egg-laying [26].

On that note, several genes that are somehow essential for oogenesis and generate unviable embryos have been identified and functionally tested in *R. prolixus.* The orthologue of Bicaudal C (*Bic*C), a gene originally identified in *D. melanogaster* involved in embryonic patterning has shown to be maternally expressed and essential for the arrangement of the follicle cells [27]. The control of iron and heme homeostasis is particularly critical for hematophagous insects, especially for the strictly hematophagous triatomines, such *R. prolixus*. In this model, the silencing of multiple iron-related genes, namely, ferritin, iron responsive protein 1 (IRP1), heme oxygenase (HO), and heme exporter feline leukemia virus C receptor (FLVCR), impairs oogenesis and embryo viability [28, 29].

The role of receptor-mediated endocytosis in yolk uptake has been investigated in oocytes of many insect species. The internalization of yolk proteins through the presence of a specialized endocytic cortex in the oocytes, which includes prominent microvilli, coated pits, coated vesicles, and endosomes have been shown in several species, including *Aedes* [30–38] However, the regulations encompassing the recruitment of the endocytic machinery to specific sites of the oocyte cortex and the signals that govern the oocyte endocytic pathways and endosomal maturation are yet to be addressed. In *R. prolixus*, ATG6/Beclin1 class-III PI3K complexes I and II were shown to be essential for YPP uptake. Insects silenced for the genes present in both complexes produce yolk-deficient eggs generating unviable embryos due to the lack of generated phosphatidylinositol-3P (PI3P) to recruit the endocytic machinery in vitellogenic oocytes [39, 40].
