The Role of ApoE Expression and Variability of Its Glycosylation in Human Reproductive Health in the Light of Current Information

Abstract

Apolipoprotein E (ApoE), a 34-kDa glycoprotein, as part of the high-density lipoprotein (HDL), has antioxidant, anti-inflammatory and antiatherogenic properties. The variability of ApoE expression in the course of some female fertility disorders (endometriosis, POCS), and other gynecological pathologies such as breast cancer, choriocarcinoma, endometrial adenocarcinoma/hyperplasia and ovarian cancer confirm the multidirectional biological function of ApoE, but the mechanisms of its action are not fully understood. It is also worth taking a closer look at the associations between ApoE expression, the type of its genotype and male fertility disorders. Another important issue is the variability of ApoE glycosylation. It is documented that the profile and degree of ApoE glycosylation varies depending on where it occurs, the type of body fluid and the place of its synthesis in the human body. Alterations in ApoE glycosylation have been observed in the course of diseases such as preeclampsia or breast cancer, but little is known about the characteristics of ApoE glycans analyzed in human seminal and blood serum/plasma in the context of male reproductive health. A deeper analysis of ApoE glycosylation in the context of female and male fertility will both enable us to broaden our knowledge of the biochemical and cellular mechanisms in which glycans participate, having a direct or indirect relationship with the fertilization process, and also give us a chance of contributing to the enrichment of the diagnostic panel in infertile women and men, which is particularly important in procedures involved in assisted reproductive techniques. Moreover, understanding the mechanisms of glycoprotein glycosylation related to the course of various diseases and conditions, including infertility, and the interactions between glycans and their specific ligands may provide us with an opportunity to interfere with their course and thus develop new therapeutic strategies. This brief overview details some of the recent advances, mainly from the last decade, in understanding the associations between ApoE expression and some female and male fertility problems, as well as selected female gynecological diseases and male reproductive tract disorders. We were also interested in how ApoE glycosylation changes influence biological processes in the human body, with special attention to human fertility.

Keywords: ApoE concentration; ApoE glycosylation; apolipoprotein E; human fertility; reproductive tract disorders.

Figure 1

Schematic structure of ApoE. Possible O-glycosylation sites: Thr8, Thr18, Thr194, Ser197, Thr289, Ser290 and Ser296 [7]. The Christchurch mutation results in a Arg136–Ser substitution [18]. Cys and/or Arg may be present at the 112th and 158th position in the amino acid chain, which determines the occurrence of the respective isoforms of ApoE [11,15]. Modification based on Liu et al. [22].

Figure 2

Main functions of ApoE in the human body.

Figure 3

Typical O-glycan structures of human ApoE. Neu5Ac—sialic acid (N-acetylneuraminic acid), Gal—galactose, GalNAc—N-acetylgalactosamine, Ser—serine, Thr—threonine. Modification based on Flowers et al. [8].