Roles of the oviduct in mammalian fertilization

Abstract

The oviduct or Fallopian tube is the anatomical region where every new life begins in mammalian species. After a long journey, the spermatozoa meet the oocyte in the specific site of the oviduct named ampulla and fertilization takes place. The successful fertilization depends on several biological processes that occur in the oviduct some hours before this rendezvous and affect both gametes. Estrogen and progesterone, released from the ovary, orchestrate a series of changes by genomic and nongenomic pathways in the oviductal epithelium affecting gene expression, proteome, and secretion of its cells into the fluid bathing the oviductal lumen. In addition, new regulatory molecules are being discovered playing important roles in oviductal physiology and fertilization. The present review tries to describe these processes, building a comprehensive map of the physiology of the oviduct, to better understand the importance of this organ in reproduction. With this purpose, gamete transport, sperm and oocyte changes in the oviductal environment, and other interactions between gametes and oviduct are discussed in light of recent publications in the field.

Figure 1

Mechanism for the sperm binding and releasing from the oviduct in the bovine model. a) Sperm binding is mediated by lectin like protein as BSP1 present in the sperm plasma membrane that recognize fucose contained in the annexin molecule bound to the epithelial cell membrane. b) Sperm binding to the oviduct could be modulated by two different mechanisms that can act at the same time. b1) Annexin present in the oviductal fluid compete for the BSP1 binding site present on the sperm. b2) Fucosidase enzymes present in the oviductal fluid can remove fucose residues contained in the annexin present in the oviductal epithelium. c) These different mechanisms and the development of hyperactivative motility allow the sperm release from the oviductal reservoir.

Figure 2

Model for the regulation of sperm capacitation. Removal of cholesterol by BSA modulates the influx of HCO⁻₃ and Ca²⁺. These ions regulate the activity of the sperm soluble adenyl cyclase (SACY), increasing intracellular cAMP and activating PKA. The activation of cSrc family kinase sensitive to both SU6656 and SKI606 down-regulates a ser/thr phosphatase, which modifies the phosphorylated steady state of PKA substrates. As a consequence, the onset of PKA phosphorylation is followed by the promotion of tyrosine phosphorylation associated with sperm capacitation. Okadaic acid is a known ser/thr phosphatase inhibitor and can induce some of the capacitation-associated processes.

Figure 3

Roles of the hyperactivation induced by the oviduct on the sperm during the approach to the oocyte: a) Detaching of the sperm from the epithelial cells; b) Transport to the fertilization site; c) Cross through cumulus cells and d) Penetration of zona pellucida.

Figure 4

Pre-fertilization ZP hardening (adapted from Coy & Avilés 2010). (1) When the oocyte is shedding in the ampulla soon after ovulation, oviduct-specific glycoprotein (OVGP1) surround it in a “shell” (2) that is responsible for the ZP resistance to proteolysis. (3) Heparin-like GAGs in the oviduct fluid stabilizes and reinforces the binding of OVGP1 with ZP, which determines the interaction of selected spermatozoa (4) with such a modified ZP. (5) In the transit towards the uterus, the system is destabilized and OVGP1 is partially unbound or internalized. (6) Thus, ZP in the embryo reaching the uterus returns to the low resistance to proteolysis showed by the ovarian oocyte in 1.

Figure 5

Progesterone (P4) levels close to the fertilization location and its effect on sperm. A) Low progesterone levels acting like a chemo-attractant driving the sperm towards the oocyte. B) High progesterone levels secreted by cumulus cells induce acrosome reaction.

Figure 6

Proposed model for the role of the plasminogen-plasmin system during fertilization. Plasminogen and plasminogen activators are present in the oolemma and ZP of the oocyte (A1). Oocyte immunostaining with antiboidies against plasminogen activators shows the oolemma strongly labeled (B1). When the spermatozoa bind the oolemma, plasminogen activators are released and increase the activation of the plasminogen into plasmin. Plasmin detaches additional spermatozoa bound to ZP (A2). The labeling in the oolema decreases a few minutes after sperm binding (B2).