In vivo and in vitro postovulatory aging: when time works against oocyte quality?

Abstract

In mammalian species an optimal fertilization window during which successful fertilization occurs. In the majority of mammals estrus marks ovulation time and coincident with mating, thereby allowing the synchronized meeting in the fallopian tubes, between freshly ejaculated sperm and freshly ovulated oocytes. Conversely, women do not show natural visual signs of ovulation such that fertilization can occur hours later involving an aged oocyte and freshly ejaculated spermatozoa. During this time, the oocyte undergoes a rapid degradation known as "postovulatory aging" (POA). POA may become particularly important in the human-assisted reproductive technologies, as the fertilization of retrieved mature oocytes can be delayed due to increased laboratory workload or because of unforeseeable circumstances, like the delayed availability of semen samples. This paper is an updated review of the consequences of POA, either in vivo or in vitro, on oocyte quality with particular attention to modifications caused by POA on oocyte nuclear, cytoplasmic, genomic, and epigenetic maturation, and embryo development.

Keywords: Antiaging chemicals; Assisted reproductive technology; Morphological alteration; Oocyte; Oxidative stress; Postovulatory aging.

Fig. 1

Main POA-related morphological and molecular alterations in mammalian oocytes. After ovulation of the MII-stage oocyte, POA-related mechanisms occur in unfertilized oocytes. Morphological alterations include ZP hardening, mt and CGs abnormal distribution patterns, CGs vacuolization, and spindle organization. On a molecular level, POA induces the increase of intracellular ROS levels and oxidative stress mechanisms, inducing lipids peroxidation, mt and DNA oxidative damages (arrows), and Ca²⁺ release from ER. Oxidative stress and cytochrome C release from mt activate apoptotic mechanisms that, together with higher intracellular Ca²⁺ levels, inactivate the cell cycle regulators (MPF, MAPK) and destabilize the epigenetic pattern (i.e., histone acetylation). Abbreviations: ATP, adenosine triphosphate; Ca²⁺, calcium; cAMP, cyclic adenosine monophosphate; Cas 3, caspase 3; CGs, cortical granules; Cyt C, cytochrome C; ER, endoplasmic reticulum; MAPK, mitogen-activated protein kinase, MII: metaphase II; MPF, maturation promoting factor; mt, mitochondria; POA, postovulatory aging; ROS, reactive oxygen species; ZP, zona pellucida

Fig. 2

Timeline of meiotic maturation and POA in in vitro studies in different mammals: human, mouse, rat, and pig. Schematic summary of the average different timings utilized for meiotic maturation and activation of POA in the in vitro studies reported in this review. For humans, see [13]. Abbreviations: GV, germinal vesicle; MI, metaphase I; MII, metaphase II; POA, postovulatory aging