Could Kallikrein-Related Serine Peptidase 3 Be an Early Biomarker of Environmental Exposure in Young Women?

Salvatore Raimondo,Tommaso Gentile,Ida Ferrara,Mariacira Gentile,Stefania De Filippo,Giusy Esposito,Luigi Montano,Claudia Crescenzo,Felice Cuomo,Marina Piscopo,Mariangela Palmieri,Gennaro Lettieri

doi:10.3390/ijerph18168833

Abstract

Bisphenols and phthalates affect androgen receptor-mediated signaling that directly regulates Kallikrein-Related serine Peptidase 3 (KLK3) secretion, indicating that environmental factors may play a role in KLK3 secretion. With the aim of obtaining preliminary data on whether KLK3 could serve as an early marker of environmental pollution effects, in 61 and 58 healthy women living in a high environmental impact (HEI) and low environmental impact (LEI) area, respectively, serum KLK3 levels at different phases of menstrual cycle were measured. KLK3 values resulted in always being higher in the HEI group with respect to the LEI group. These differences were particularly relevant in the ovulatory phase (cycle day 12°–13°) of the menstrual cycle. The differences in KLK3 values during the three phases of the menstrual cycle were significant in the LEI group differently from the HEI group. In addition, higher progesterone levels were observed in the LEI group with respect to the HEI group in the luteal phase, indicating an opposite trend of KLK3 and progesterone in this phase of the menstrual cycle. Although changes in KLK3 could also depend on other factors, these preliminary data could be an early indication of an expanding study of the role of biomarkers in assessing early environmental effects for female reproductive health.

Highlights

Kallikreins are a subgroup of serine proteases responsible for various physiological functions and are capable of cleaving peptide bonds in proteins
The purpose of this study is to provide preliminary data on the possible role of KLK3 as a new biomarker to assess the early effects of environmental exposure for female reproductive health
In 14 out of 58 participants belonging to the low-impact group (24.1%), and in 17 out of 61 participants belonging to the high-impact group (27.8%), KLK3 was not detectable in any of the three samples per menstrual cycle with the method we used

Summary

Introduction

Kallikreins are a subgroup of serine proteases responsible for various physiological functions and are capable of cleaving peptide bonds in proteins. Plasma kallikrein (KLKB1) has no known homologs, whereas tissue peptidase-related kallikrein (KLKs) constitute a family of 15 highly conserved serine proteases. These genes are localized on chromosome 19q13, forming the largest contiguous group of proteases in the human genome. The 15 members of the kallikrein-related serine peptidase (KLK) have different tissue-specific expression profiles. KLK3 was believed to be absent from female tissues and fluids. The presence of KLK3 in these female tissues appears to be closely associated with

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