Celine Jones

Comparative biology of sperm factors and fertilization-induced calcium signals across the animal kingdom.

Fertilization causes mature oocytes or eggs to increase their concentrations of intracellular calcium ions (Ca2+) in all animals that have been examined, and such Ca2+ elevations, in turn, provide key activating signals that are required for non‐parthenogenetic development. Several lines of evidence indicate that the Ca2+ transients produced during fertilization in mammals and other taxa are triggered by soluble factors that sperm deliver into oocytes after gamete fusion. Thus, for a broad‐based analysis of Ca2+ dynamics during fertilization in animals, this article begins by summarizing data on soluble sperm factors in non‐mammalian species, and subsequently reviews various topics related to a sperm‐specific phospholipase C, called PLCζ, which is believed to be the predominant activator of mammalian oocytes. After characterizing initiation processes that involve sperm factors or alternative triggering mechanisms, the spatiotemporal patterns of Ca2+ signals in fertilized oocytes or eggs are compared in a taxon‐by‐taxon manner, and broadly classified as either a single major transient or a series of repetitive oscillations. Both solitary and oscillatory types of fertilization‐induced Ca2+ signals are typically propagated as global waves that depend on Ca2+ release from the endoplasmic reticulum in response to increased concentrations of inositol 1,4,5‐trisphosphate (IP3). Thus, for taxa where relevant data are available, upstream pathways that elevate intraoocytic IP3 levels during fertilization are described, while other less‐common modes of producing Ca2+ transients are also examined. In addition, the importance of fertilization‐induced Ca2+ signals for activating development is underscored by noting some major downstream effects of these signals in various animals. Mol. Reprod. Dev. 80: 787–815, 2013.

Deleterious effects of obesity upon the hormonal and molecular mechanisms controlling spermatogenesis and male fertility

Abstract Worldwide obesity rates have nearly doubled since 1980 and currently over 10% of the population is obese. In 2008, over 1.4 billion adults aged 20 years and older had a body mass index or BMI above a healthy weight and of these, over 200 million men and nearly 300 million women were obese. While obesity can have many ramifications upon adult life, one growing area of concern is that of reproductive capacity. Obesity affects male infertility by influencing the hypothalamic–pituitary–gonadal axis, thus causing detrimental effects upon spermatogenesis and subsequent fertility. In particular, evidence indicates that excess adipose tissue can alter the relative ratio of testosterone and oestrogen. Additional effects involve the homeostatic disruption of insulin, sex-hormone-binding-globulin, leptin and inhibin B, leading to diminished testosterone production and impairment to spermatogenesis. Aberrant spermatogenesis arising from obesity is associated with downstream changes in key semen parameters, defective sperm capacitation and binding, and deleterious effects on sperm chromatin structure. More recent investigations into trans-generational epigenetic inheritance further suggest that molecular changes in sperm that arise from obesity-related impaired spermatogenesis, such as modified sperm RNA levels, DNA methylation, protamination and histone acetylation, can impact upon the development of offspring. Here, we summarise our current understanding of how obesity exerts influence over spermatogenesis and subsequent fertility status, and make recommendations for future investigative research.

Calcium Oscillations, Oocyte Activation, and Phospholipase C zeta

In mammals, gamete fusion initiates a succession of oscillations in the intracellular concentration of calcium within the oocyte, prompting a series of events to occur that are collectively known as oocyte activation. Such events are a fundamental necessity for the initiation of cell division and subsequent embryogenesis. Compelling evidence now indicates that these calcium oscillations are caused by a testis-specific phospholipase C (PLC) termed PLCzeta (PLCζ), released into the oocyte following gamete fusion. A series of recent studies indicate that abnormal expression or aberrant activity of PLCζ is linked to certain types of human male infertility, where oocyte activation ability is impaired or absent altogether. In this chapter, we discuss the critical role of calcium oscillations in the process of oocyte activation, review the role of PLCs in this fundamental biological reaction, describe how PLCζ has been formally linked to male infertility, and postulate the potential roles for PLCζ in terms of clinical diagnosis and therapy.