Hypoxia, NSAIDs, and autism: A biocultural analysis of stressors in gametogenesis

Cultural and generational trends have increasingly favored "anti-inflammatory" action, innovating a new class of analgesic, non-steroidal anti-inflammatory drugs (NSAIDs) in the 20th century. The modern human body has been molded over evolutionary time and while acknowledging inflammation can be pathologically entwined, it also serves an important role in healthy folliculogenesis and ovulation, shaping cues that drive needed vascular change. This review argues that because of anti-inflammatory action, the cultural invention of NSAIDs represents a particular stressor on female reproductive-age bodies, interacting with natural, underlying variation and placing limits on healthy growth and development in the follicles, creating potential autism risk through hypoxia and mutagenic or epigenetic effects. Since testes are analogs to ovaries, the biological grounding extends naturally to spermatogenesis. This review suggests the introduction of over-the-counter NSAIDs in the 1980s failed to recognize the unique functioning of reproductive-age bodies, challenging the cyclical inflammation needed for healthy gamete development. NSAIDs are framed as one (notable) stressor in an anti-inflammatory era focused on taming the risks of inflammation in modern human life.