Greater Loss of Female Embryos During Human Pregnancy: A Novel Mechanism

Abstract

Given an equal sex ratio at conception, the excess of human males at birth can only be explained by greater loss of females during pregnancy. It is proposed that the bias against females during human development is the result of a greater degree of genetic and metabolic "differentness" between female embryos and maternal tissues than for similarly aged males, and that successful implantation and placentation represents a threshold dichotomy, where the acceptance threshold shifts depending on maternal condition, especially stress. Right and left ovaries are not equal, and neither are the eggs and follicular fluid that they produce, and it is further hypothesized that during times of stress, the implantation threshold is shifted sufficiently to favor survival of females, most likely those originating from the right ovary, and that this, rather than simply a greater loss of males, explains at least some of the variability in the human sex ratio at birth.

Stressor Effects on Sex Ratios and Births in the Maltese Population during the First Half of the 20th Century

“…With a reported miscarriage rate of approximately 25% and the larger majority occurring in the first trimester (26), the disproportionate loss of female fetuses results in a significant deficit that persists right through the perinatal period even though proportionately more male fetuses are lost during the third trimester and neonatal period. The reasons for the proportionately excessive female wastage in the first trimester have not been completely elucidated (27). However, its evolutionary purpose may be to ensure that the healthiest females survive to ensure effective reproductive capabilities.…”

Role of omega‐6 and omega‐3 fatty acids in fetal programming

“…Additional studies are underway exploring how such sex differences may impact survivability and programmed disease in offspring. 93 Studies have shown that the sex ratio of offspring is particularly sensitive to exposure to fatty acids in pregnancy. In opossums, maternal diets supplemented with sardines resulted in the male-biased sex ratio.…”

“…If this occurs early in pregnancy, before recognition of pregnancy, this may appear as though male fetuses were never conceived. Additional studies are underway exploring how such sex differences may impact survivability and programmed disease in offspring …”

Designing Effective Multi-Target Drugs and Identifying Biomarkers in Recurrent Pregnancy Loss (RPL) Using In Vivo, In Vitro, and In Silico Approaches

“…Moreover, recurrent pregnancy loss involves a cascade of physiological reactions as well as the activation of numerous signaling pathways, and the NF-κB (nuclear factor-κB) pathway is a crucial pathway. Although, the NF-κB pathway’s function in different biological processes is debatable; on the one hand, it can promote host defense and other protective cellular responses, while on the other, its activation contributes to inflammatory harm in tissues [ 7 ]. It is not unexpected that the NF-κB pathway impacts mitochondrial function and architecture as the NF-κB pathway serves as a transcription factor of the oxidative stress reaction [ 8 ].…”