Male Infertility Risk Factors and Therapy

**3**

**Chapter 1**

**Abstract**

to childhood development.

**1. Introduction**

The Early Life Influences on Male

Increasing concern exists regarding male reproductive health worldwide. This is due to the appearance of medical reports outlining apparent adverse trends, such as a worldwide decline in total fertility rate, and an increase in testicular disorders such as testicular cancer, cryptorchidism—in parallel with a probable decline in semen quality. This is of particular concern as there is evidence to suggest that a poor sperm count is potentially associated with overall lifelong morbidity and mortality, and is effectively a predictor of lifelong health risk. This chapter examines the evidence for this decline and its potential early life causes, from in-utero exposures

**Keywords:** male reproduction health, sperm, testosterone, in-utero, phthalate, BPA

Between 1986 and 1993, British physician and epidemiologist David Barker published a series of articles in the Lancet, proposing his hypothesis of the foetal origins of adult health and disease [1–3]. In these publications, he argued that adverse alterations in the developmental early life environment *in utero*, had potential to induce and initiate phenotypic and adaptive changes affecting an individual's responses to their later life environment, which might prove maladaptive when the early and late environments were markedly different [4, 5]. Barker's specific foetal concerns were inadequate nutrition, [6] intrauterine growth retardation, low birth weight and premature birth and their causal relationship to the origins of hypertension, coronary heart disease and non-insulin-dependent diabetes, in later life [7]. However there is now growing evidence to suggest that this 'developmental programming' and the foetal environment, which includes placental function, maternal metabolism, exposures and lifestyle factors (including maternal smoking), may influence additional systems including reproductive health and development in both males and females [5, 8]. Increasing concern exists regarding male reproductive health worldwide due to the appearance of medical reports outlining apparent adverse trends, in the context of a worldwide decline in total fertility rate (**Figure 1**) [9, 10]. This includes an increase in the incidence of the proposed 'testicular dysgenesis syndrome' [10] which encompasses a constellation of testicular disorders including testicular cancer, [11, 12] cryptorchidism and hypospadias [13]. This is in parallel with population-based evidence to suggest declining semen quality, [14] alterations in serum testosterone levels and a change in the timing of onset of male puberty [9]. Worryingly, one comprehensive review of the literature proposed that semen quality had declined by 52.4% between 1973 and 2011 among unselected men from Western countries [14]. Another recent report, published

Reproductive Health

*Jennifer Pontré and Roger Hart*

## **Chapter 1**
