**7. Conclusions**

Autophagy mediates a variety of life process, including cancer development, immune response, and aging pathophysiology [88]. Autophagy decreases with age, which coincides with the increases in neurodegenerative diseases we observe in the elderly. Because aging is an independent risk factor for preeclampsia, these concepts may be linked. The decrease of autophagic activity with aging, which results in susceptibility to endotoxin-induced inflammation, and the inflammation related to preeclampsia, might gradually increase risk for systemic inflammation in older pregnan<sup>t</sup> women [89]. This suggests pharmacological manipulation of autophagy may treat preeclampsia. In addition, autophagy activation might prevent premature labor not caused by bacterial infection. However, these theories are untested, so it remains unclear whether autophagy activation is favorable or unfavorable for preeclampsia, FGR, and other pregnancy-related diseases. To solve this question, the placental characteristics that regulate autophagy may need to be segmentalized: age, body mass index, severity, time of onset, genetic background, microvesicles, immune status, and origin of eggs. Finally, technical advances are needed to enable precise measurement of autophagy before it can be manipulated in clinical research.

**Funding:** The series of this study was supported by AMED-CREST from the Japan Agency for Medical Research and Development, AMED 16gk0110018h0001, grants from the Kanzawa Medical Research Foundation, Tamura Science and Technology Foundation, Yamaguchi Endocrine Research Foundation, First Bank of Toyama, Toyama University Hospital Grant, 040200-59200003502, and JSPS KAKENHI Grant Numbers JP17K11221 and JP19K09750. **Conflicts of Interest:** The authors declare no conflict of interests. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
