Absorption, distribution, metabolism and excretion of hyaluronic acid during pregnancy: a matter of molecular weight

ABSTRACT

Introduction

For many years hyaluronic acid (HA) was mainly used for its hydrating properties. However, new applications have recently arisen, considering the biological properties of HA and its molecular weight. Clinical application of low molecular weight HA (LMW-HA) initially was supported by specific absorption data. The identification of high molecular weight HA (HMW-HA) absorption pathways and the knowledge of its physiological role allowed to evaluate its clinical application. Based on the immunomodulatory properties of HMW-HA and its physiological involvement as signaling molecule, pregnancy represents an interesting context of application.

Area covered

This expert opinion includes in-vitro, in-vivo, ex-vivo and clinical studies on gestational models. It provides an overview of the physiological and the therapeutic role of HMW-HA in pregnancy starting from its metabolism. Indeed, HMW-HA is widely involved in several physiological processes as implantation, immune response, uterine quiescence and cervical remodeling, and therefore is an essential molecule for a successful pregnancy.

Expert opinion

Available evidence suggests that HMW-HA administration can support physiological pregnancy, favoring blastocyst adhesion and development, preventing miscarriage and pre-term birth. For this reason, supplementation in pregnancy should be evaluated.

KEYWORDS:

• Hyaluronic acid
• high-molecular-weight hyaluronic acid
• absorption
• pregnancy
• recurrent miscarriage
• preeclampsia
• pre-term birth

Article highlights

• Hyaluronic acid (HA) is a mucopolysaccharide, occurring naturally in all living organisms. It is formed by multiple repetition of 3-D-glucuronic acid and D-N-acetylglucosamine moieties and ranges from 2 to more than 10,000 disaccharide units. Based on its molecular weight, HA exhibits different biological roles.

• High molecular weight HA (HMW-HA) is physiologically involved in several phases of pregnancy from fertilization to blastocyst implantation, uterine contraction inhibition, immunomodulation of T cells and to labor-related cervical modifications.

• HA absorption depends on its molecular weight. Oligomers of HA (O-HA) can passively permeate through the intestinal barrier between the enterocytes, reaching the blood stream. On the other hand, HMW-HA (>10 kDa) can be absorbed undegraded by microfold cells in the intestine, and transported to the gut-associated lymphatic tissue.

• Clinical applications of HMW-HA in pregnancy represent for a potential treatment for recurrent miscarriage, preeclampsia, and pre-term birth.

Declaration of interest

Vittorio Unfer and Marco Tilotta are employees at LO.LI. Pharma S.R.L. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.