Sex dimorphic associations of Prader-Willi imprinted gene expressions in umbilical cord with prenatal and postnatal growth in healthy infants.

Background: The impact of Prader-Willi syndrome (PWS) domain gene expression on the growth of healthy children is not well understood. This study investigated associations between PWS domain gene expression in umbilical cord tissue and prenatal and postnatal growth, considering potential sex differences.
Methods: Relative gene expression of paternally expressed MAGEL2, NDN, and SNURF-SNRPN, and the small nucleolar RNAs SNORD116 and SNORD115 were determined by real-time quantitative polymerase chain reaction in umbilical cord tissue from 122 healthy newborns (59 girls and 63 boys). Gene expression levels were correlated with auxological measures at birth, infancy, and childhood (ages 2, 4, and 6 years).
Results: MAGEL2, NDN, SNORD116, and SNORD115 expression in the umbilical cord was negatively associated with birth weight, length, and placental weight (P < 0.001). Postnatally, these genes were positively associated with weight and length at 3 months (P < 0.001) and weight gain from birth to ages 1, 2, and 4 years (P < 0.01). Negative associations at birth were stronger in girls (P < 0.001), while positive associations during infancy and childhood were stronger in boys (P < 0.001). MAGEL2, SNORD116, and SNORD115 expression predicted early-postnatal growth, explaining the higher growth rate in boys compared to girls and accounting for sex differences up to 1.5 kg in weight and 3 cm in height during infancy.
Conclusions: Paternally expressed PWS domain gene expression in the umbilical cord was negatively associated with prenatal growth and positively with early-postnatal growth in healthy infants. This gene expression may predict early human postnatal growth and promote the well-known sex dimorphism in growth. These results can also help in understanding the etiology of PWS, which remains unclear.
Competing Interests: Declarations. Ethical approval: The protocol was approved by the Institutional Review Board of Dr. Josep Trueta Hospital (CEIC 26/03/2019 2019.053). Informed consent to participate in the study has been obtained from the participants (or their parent or legal guardian in the case of children under 16). Conflict of interest: HAM has served as a Principal Investigator for Rhythm Pharmaceuticals, Acadia Pharmaceuticals, Levo Therapeutics and Eli Lilly; has received consulting fees from Rhythm Pharmaceuticals, Pfizer Canada, Novo Nordisk Canada; has received honoraria from Rhythm Pharmaceuticals; has participated on an Advisory board for Rhythm Pharmaceuticals, Novo Nordisk Canada. The remaining authors report no conflict of interest.
(© 2025. The Author(s).)