Does high molecular weight-hyaluronic acid prevent hormone-induced preterm labor in rats?

Eur Rev Med Pharmacol Sci. 2023 Apr;27(7):3022-3032. doi: 10.26355/eurrev_202304_31936.


Objective: The aim of our study was to test if oral high hyaluronic acid (HMW-HA) administration was effective in contrasting induced preterm birth (PTB) in female Wistar rats.

Materials and methods: A total of 24 pregnant rats were pretreated with placebo or low (2.5 mg/day)/high dose (5 mg/day) of HMW-HA (day 15) and then induced to delivery with mifepristone plus prostaglandin E2 (PGE2) (3 mg/100 µL + 0.5 mg/animal) on the 19th day of pregnancy. The delivery time was recorded and the messenger RNA (mRNA) levels of pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin (IL)1β, IL-6] were detected in the uterine tissues by real-time polymerase chain reaction (real PCR). Immunohistochemistry was performed alongside.

Results: Oral HMW-HA was well absorbed in the body and was able to significantly delay the timing of delivery and decrease mRNA synthesis of pro-inflammatory cytokines.

Conclusions: HMW-HA, by acting in the management of PTB, may represent a new approach to protecting physiological pregnancy.

MeSH terms

  • Animals
  • Cytokines / genetics
  • Female
  • Hormones
  • Humans
  • Hyaluronic Acid / adverse effects
  • Infant, Newborn
  • Inflammation / pathology
  • Molecular Weight
  • Obstetric Labor, Premature*
  • Pregnancy
  • Premature Birth* / prevention & control
  • RNA, Messenger / genetics
  • Rats
  • Rats, Wistar
  • Tumor Necrosis Factor-alpha / adverse effects


  • Hyaluronic Acid
  • Cytokines
  • Tumor Necrosis Factor-alpha
  • RNA, Messenger
  • Hormones