Effect of a High Estrogen Level in Early Pregnancy on the Development and Behavior of Marmoset Offspring

[Image: see text] The use of assisted reproductive technology (ART) has risen steadily worldwide over the past 3 decades and helps many infertile families. However, ART treatments lead to an abnormal internal environment in the uterus, which may increase the risks of health problems for the offspring. Higher maternal estradiol (E(2)) is a notable feature in women who use ART treatments, and this has been suggested as a key factor for the risk of diseases in the offspring. In the current study, we have established a marmoset model with a high E(2) level in early pregnancy to examine its potential risk to the development and behavior of the offspring. In comparison with the normal group, babies of the high E(2) group exhibited lower average survival rates and birth weights. However, those who survived in the high E(2) group demonstrated normal vocal production with rich call repertoires, normal speed during locomotion, and normal behaviors in the home cage. In contrast to the normal group, surviving babies of the high E(2) group spent more time sleeping during development without signs of sleep disorders. In summary, our study revealed that high estrogen in early pregnancy may cause low survival rates and birth weights of the offspring, though the surviving infants did not show obvious behavioral deficiencies during development. The current study is a valuable and highly important non-human primate study for evaluating the safety of ART treatments. However, it is worth noting that some results did not reach the significant level, which may be due to the small sample size caused by animal shortage stemming from the COVID-19 epidemic.