Sex-biased regulatory changes in the placenta of native highlanders contribute to adaptive fetal development

Compared with lowlander migrants, native Tibetans have a higher reproductive success at high altitude though the underlying mechanism remains unclear. Here, we compared the transcriptome and histology of full-term placentas between native Tibetans and Han migrants. We found that the placental tropho...

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Bibliographic Details
Published in:eLife 2024-06, Vol.12
Main Authors: Yue, Tian, Guo, Yongbo, Qi, Xuebin, Zheng, Wangshan, Zhang, Hui, Wang, Bin, Liu, Kai, Zhou, Bin, Zeng, Xuerui, Ouzhuluobu, He, Yaoxi, Su, Bing
Format: Article
Language:English
Subjects:
Adaptation
Altitude
Animal reproduction
Birth weight
Breeding success
Divergence
Endoplasmic reticulum
Evolutionary Biology
Female
Females
Fetal Development - genetics
Fetuses
Gene expression
genetic adaptation
Genomes
high altitude
Humans
Hypoxia
Immune response
Infant, Newborn
Infants
Male
Mothers
Neonates
Placenta
Placenta - metabolism
Population genetics
Population studies
Pregnancy
Principal components analysis
Sex
sex bias
Sex Characteristics
Sex Factors
Tibet
Tibetan
Transcriptome
Transcriptomes
Umbilical cord
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Summary:Compared with lowlander migrants, native Tibetans have a higher reproductive success at high altitude though the underlying mechanism remains unclear. Here, we compared the transcriptome and histology of full-term placentas between native Tibetans and Han migrants. We found that the placental trophoblast shows the largest expression divergence between Tibetans and Han, and Tibetans show decreased immune response and endoplasmic reticulum stress. Remarkably, we detected a sex-biased expression divergence, where the male-infant placentas show a greater between-population difference than the female-infant placentas. The umbilical cord plays a key role in the sex-biased expression divergence, which is associated with the higher birth weight of the male newborns of Tibetans. We also identified adaptive histological changes in the male-infant placentas of Tibetans, including larger umbilical artery wall and umbilical artery intima and media, and fewer syncytial knots. These findings provide valuable insights into the sex-biased adaptation of human populations, with significant implications for medical and genetic studies of human reproduction.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.89004