Oviduct epithelium interactions: roles in sperm selection and embryo quality

Abstract

This review provides an up-to-date overview of the roles of the oviduct during the periconception period and underlying mechanisms. The functions of the oviduct before, during, and after fertilization are highlighted, with special focus on the effects of epithelial cell contact and luminal secretions on sperm selection mechanisms and acquisition of fertilization ability. The current knowledge on how the oviduct contributes to support fertilization and embryo development via the overall physical milieu (oxygen tension, fluid current, ciliated epithelial cells) and the role of its secretions is also provided. Altogether, the review underlines the unique role of the oviduct during gamete selection and early embryo development, which so far has not been completely possible to mirror when assisted reproductive technologies (ART) are used. Unveiling the most important functional components of oviductal secretions that contribute to better sperm selection, and boost sperm fertilizing ability and early embryo development, can indeed be useful to improve the outcomes of current in vitro systems used in ART.

Keywords: embryo; fallopian tube; gamete; oviduct; spermatozoa.

Figure 1. Cross-section of a bovine ampulla at the pre-ovulatory stage of cycle. Green = pan cytokeratin (epithelial cell marker); blue = nuclei (Hoechst staining). (A) smooth muscle; (B) epithelium; (C) lumen; (D) stroma.

Figure 2. Morphological and molecular factors for sperm passage through the utero-tubal junction. In mice, only highly motile sperm with an intact acrosome can pass the utero-tubal junction (Hourcade et al., 2010; Muro et al., 2016). Sperm from mice deficient for 22 genes, including 19 involved in Adam3 expression (in black) and 3 Adam3-independent ones (in red), were not able to cross the utero-tubal junction (Fujihara et al., 2018, 2019; Larasati et al., 2020; Xiong et al., 2019), suggesting their involvement in sperm migration toward the oviduct.

Figure 3. Bull sperm bound to motile cilia of the oviduct epithelium. (A) Scanning electron microscopy picture obtained after co-incubation of frozen-thawed density gradient-washed bull sperm with isthmic epithelial spheroids in a non-capacitating medium; (B) Higher magnification showing a sperm bound with its head to the distal extremity of motile cilia. Microvilli at the surface of secretory non-ciliated cells are seen around the sperm head. Note that all spermatozoa are acrosome-intact with a normal morphology.

Figure 4. Proteins and phospholipids identified for sperm binding to oviduct epithelial cells Two ligand-receptor couples have been identified so far: the integrin α5β1-fibronectin couple in cattle (brown, on the left; Osycka-Salut et al., 2017) and the phosphatidylserine (PS)-annexin A5 couple in pigs (purple, on the right; Schmaltz et al., 2024a). Proteins from the seminal plasma, including binder of sperm proteins (BSP) 1,3 and 5 in cattle (green, on the left; Gwathmey et al., 2006) and aquaporin (AQN1; Ekhlasi-Hundrieser et al., 2005) in pigs (blue, on the right) have been proposed as additional sperm ligands to cilia. On the female side, several annexins (ANX) were identified as sperm receptors in cattle and pigs (in purple, on cilia) (Ignotz et al., 2007; Teijeiro et al., 2009; Schmaltz et al., 2024a). In addition, boar sperm bind specifically to specific glycans, including Lewis X trisaccharide (Le^X), 3'-O-sulfated form of Le^X, and 6-sialylated N-acetyllactosamine (bi-SiaLN), while bull sperm bound 3'-O-sulfated form of Lewis A trisaccharide (Kadirvel et al., 2012; Machado et al., 2014; Dutta et al., 2019a).

Figure 5. Molecular signals inducing sperm release from oviduct epithelial cells. Progesterone in cattle (Lamy et al., 2017; Romero-Aguirregomezcorta et al., 2019) and pigs (Machado et al., 2019); natriuretic peptide type C (NPCC) in mice (Wang et al., 2022) and pigs (Wu et al., 2023); sulfated glycosaminoglycans in cattle (Mahe et al., 2023b; Talevi and Gualtieri, 2001); fibronectin in cattle (Osycka-Salut et al., 2017, 2020).

Figure 6. Bright-field picture of a bovine hatching blastocyst (on the right) that developed in co-culture with isthmic epithelial spheroids (two are visible on the left) maintained in suspension in the culture medium thanks to outward ciliary beating.