Review or Mini-review
Effects of glyphosate exposure on sperm concentration in rodents: A systematic review and meta-analysis

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Abstract

Background

Correlation between exposure to glyphosate and sperm concentrations is important in reproductive toxicity risk assessment for male reproductive functions. Many studies have focused on reproductive toxicity on glyphosate, however, results are still controversial. We conducted a systematic review of epidemiological studies on the association between glyphosate exposure and sperm concentrations of rodents. The aim of this study is to explore the potential adverse effects of glyphosate on reproductive function of male rodents.

Methods

Systematic and comprehensive literature search was performed in MEDLINE, TOXLINE, Embase, WANFANG and CNKI databases with different combinations of glyphosate exposure and sperm concentration. 8 studies were eventually identified and random-effect model was conducted. Heterogeneity among study results was calculated via chi-square tests. Ten independent experimental datasets from these eight studies were acquired to synthesize the random-effect model.

Results

A decrease in sperm concentrations was found with mean difference of sperm concentrations(MDsperm) = −2.774 × 106/sperm/g/testis(95%CI = −0.969 to −4.579) in random-effect model after glyphosate exposure. There was also a significant decrease after fitting the random-effect model: MDsperm = −1.632 × 106/sperm/g/testis (95%CI = −0.662 to −2.601).

Conclusions

The results of meta-analysis support the hypothesis that glyphosate exposure decreased sperm concentration in rodents. Therefore, we conclude that glyphosate is toxic to male rodent’s reproductive system.

Introduction

Glyphosate [N-(phosphonomethyl) glycine] is one of the most broad-spectrum pesticides, and one of the mostly used herbicides in agriculture globally. Glyphosate is the primary active ingredient in Round up® branded herbicides produced by Monsanto. With rapid popularization of transgenic glyphosate-resistant crops, the amount of glyphosate continue to increase worldwide. Glyphosate has increased by about 20% annually. It is not only the world's largest pesticide production and consumption varieties, but also China's fastest growing, highest output, and the largest export varieties of pesticides.

Glyphosate has been applied in many areas and causes serious pollution to soil and nearby ecosystems, and eventually increases the risk to human (Williams et al., 2000). For the past few years, researchers have paid attention to reproductive toxicity induced by glyphosate and Round up®. Exposure to glyphosate has been associated with many adverse effects on male reproductive system in both humans and rodents (de Brito Rodrigues et al., 2016, Williams et al., 2016b). In mammals, particularly rats, glyphosate could alter sperm characteristics including sperm production, and even fetal development (Chan and Mahler, 1992, Gasnier et al., 2009). Glyphosate causes libido and decreases ejaculate volume and sperm concentration in New Zealand rabbits, possibly due to direct cytotoxic effect of glyphosate on spermatogenesis or indirectly through the effect of hypothalamic pituitary testicular axis (Richard et al., 2005). So far, reported male toxic effects and risk assessment include reduced ejaculate volume, testosterone concentration, sperm production of the seminiferous epithelium, sperm concentration, sperm morphology, sperm motility and sperm aberration rate. The most frequently reported semen characteristic is sperm concentration in humans and rodents among these measurements.

However, other researchers have found contradictory conclusions. In Wlliams's review, the authors raised questions about reproductive toxicity of glyphosate in animals, and there was no definitive evidence that glyphosate or Roundup herbicide adversely impacted reproductive function (Williams et al., 2000). Besides, in other reproductive toxicity studies in rodents, no adverse effects have been observed: there was no difference in viability and mobility and sperm concentration, only an increase of abnormal sperm morphology at day 87 and day 122 after an acute exposure to glyphosate-based herbicide in both rats and mice experiments (Cassault-Meyer et al., 2014).

Therefore, potential detrimental effects of glyphosate on sperm concentration have been reported by a number of studies, however the results are inconsistent and controversial. In order to systematically evaluate our current knowledge in this field and provide accurate evidence on the influence of glyphosate exposure to male reproductive system, we conduct a systematic review and meta-analysis of several animal experiment studies to assess the effect of glyphosate exposure on rodents’ sperm concentration. This is the first meta-analysis to synthesize reproductive effects of glyphosate exposure in a rodent model.

Section snippets

Literature search strategy

We performed a comprehensive literature search on the association between glyphosate exposure on rodents and change of sperm concentration. The search was conducted in Pub Med, Web of Sciences, MEDLINE, TOXLINE, Embase, CNKI and Wanfang databases from January 1990 up to November 26,2016, with a combination of the following keywords: glyphosate; round up; reproductive toxicity; testicular; testes; sperm reserves; sperm quality sperm concentrations; male; animal; rats; and mice. Besides; we

Literature search

Search through MEDLINE, TOXLINE, and Embase databases yielded 56 unique articles (Fig. 1). 10 additional publications were identified through CNKI and Wanfang database. After screening their abstracts, titles, and whole article, 57 papers were excluded because the results were based on population (21 studies); outcomes were irrelevant to reproduction (18 studies); and studies focused on toxicity of glyphosate to sperm atogonia (13 studies). A final set of 8 papers on sperm concentration

Discussion

There is still controversy on whether glyphosate exposure could cause cancer in humans or animals, as well as other non-cancer diseases (Williams et al., 2016a, Williams et al., 2016b). Recent study has reported that glyphosate could cause weight loss, decreased libido, poor ejaculate volume and low sperm concentrations following a dose-dependent manner in male New Zealand white rabbits, accompanied by increased abnormal and dead sperms (Yousef et al., 1995). Decreasing sperm concentration is

Disclosure statement

The authors declare that there is no financial conflict of interest.

Acknowledgements

This work was supported by the Jiangsu Provincial Medical Innovation Team (CXTDA2017029), the Clinical Medical Special Foundation of Jiangsu Province (Grant No. BL2014082), the Natural Science Foundation of Jiangsu Province(BK20151594), the six talent peaks project in Jiangsu Province (WSW-017), the National Science Foundation for Young Scientists of China (Grant No. 81502796), the Natural Science Foundation for Young Scientists of Jiangsu Province (Grant No. BK20171076), and the Jiangsu

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    Herbicides are weed control agents that are practically indispensable for commercial farmers. The non-selective, post-emergence, systemic herbicide glyphosate [N-(phosphonomethyl) glycine; Gly] dominates the herbicide market since it controls more weed species than any other herbicide [1,2]. Intensive use of Gly-based herbicides is followed by the widespread adoption of Gly-tolerant crops, which correspond to approximatelly 90% of the livestock diet in North America.

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