Florence Eustache

Bio: Florence Eustache is an academic researcher from University of Paris. The author has contributed to research in topics: Sperm & Fertility preservation. The author has an hindex of 11, co-authored 30 publications receiving 1025 citations.

Regional differences in semen quality in Europe.

Abstract: Recent reports have indicated a decrease in semen quality of men in some countries, and suggested regional differences. A study was undertaken of semen samples from 1082 fertile men from four European cities (Copenhagen, Denmark; Paris, France; Edinburgh, Scotland; and Turku, Finland). Semen analysis was standardized, inter-laboratory differences in assessment of sperm concentration were evaluated, and morphology assessment centralized. Lowest sperm concentrations and total counts were detected for Danish men, followed by French and Scottish men. Finnish men had the highest sperm counts. Men from Edinburgh had the highest proportion of motile spermatozoa, followed by men from Turku, Copenhagen and Paris. Only the differences between Paris/Edinburgh and Paris/Turku were statistically significant (P < 0.003 and P < 0.002 respectively). No significant differences in morphology were detected. A general seasonal variation in sperm concentration (summer 70% of winter) and total sperm count (summer 72% of winter) was detected. Semen quality of a 'standardized' man (30 years old, fertile, ejaculation abstinence of 96 h) were estimated. Typically, sperm concentrations (x 10(6)/ml) for winter/summer were: Turku 132/93; Edinburgh 119/84; Paris 103/73; and Copenhagen 98/69. These differences in semen quality may indicate different environmental exposures or lifestyle changes in the four populations. However, it remains to be seen whether such changes can account for these differences. These data may also serve as a reference point for future studies on time trends in semen quality in Europe.

Chronic Dietary Exposure to a Low-Dose Mixture of Genistein and Vinclozolin Modifies the Reproductive Axis, Testis Transcriptome, and Fertility

Abstract: Estrogenic and antiandrogenic endocrine-disrupting compounds (EDCs) cause a wide spectrum of developmental and fertility detrimental effects [for review, see Sharpe (2003) and Gray et al. (2001), respectively]. Most studies have used high doses of a single compound and short exposure periods, generally during the critical uterine or neonatal period. However, humans and wild animals are exposed simultaneously to various environmental and food EDCs, generally at low levels, throughout their lives. Therefore, it would be valuable to determine the effects of a chronic exposure to low doses of EDCs on the reproductive axis and to identify the mechanisms involved. In particular, it is not known whether lifetime exposures to low (environmental) doses of estrogenic “feminizing” and antiandrogenic “demasculinizing” EDCs can have adverse effects on male reproductive function of the same magnitude as those of acute exposure to high nonenvironmental doses of these compounds in isolation. In this study, we used a rat model of prolonged exposure to EDCs by gavage to determine the effects on male reproduction of two EDCs that may be associated in the human diet: the phytoestrogen genistein and the antiandrogenic fungicide vinclozolin. Genistein is an estrogenic isoflavonoid found in leguminous plants (Breinholt et al. 2000). It is particularly abundant in diets containing soya or soya-derived products, leading to a dietary exposure of up to 2 mg/kg body weight/day; for infants fed milk formulas containing soya, dietary exposure can reach 1 mg/kg body weight/day (Setchell et al. 1998). In previous studies involving transient gestational, lactational, or adult intakes (Santti et al. 1998), rodents have been exposed to various doses of genistein but the findings are equivocal: some report male reproductive anomalies (Wisniewski et al. 2003), whereas other do not (Faqi et al. 2004; Jung et al. 2004). Human exposure to genistein may affect the responsiveness and sensitivity to other xenobiotics, particularly environmental estrogenic chemicals (You et al. 2002) and other endocrine-active dietary contaminants. Vinclozolin, a dicarboximide fungicide extensively used on fruit and vegetables, is recognized as a human diet contaminant acting—essentially through its two main metabolites M1 and M2—as an androgen-receptor (AR) binding antagonist (Kelce et al. 1994, 1997; Nellemann et al. 2003). A recent French study reported that 20% of 139 meal samples from work canteens contained measurable levels of vinclozolin (Leblanc et al. 2000). In addition, assays of metabolites in urine revealed that > 80% of a population in central Italy was exposed to noticeable levels of vinclozolin and similar pesticides (Turci et al. 2006). Vinclozolin administered to experimental animals in vivo at various doses, by various routes, and for exposure periods (gestation, lactation, puberty, adulthood) produces a wide spectrum of reproductive defects: reduced anogenital distance (AGD); persistent nipples; cleft phallus; hypospadias; cryptorchidism; reduced weights of the ventral prostate, seminal vesicles, and epididymis; and reduced sperm counts (Gray et al. 1999; Monosson et al. 1999; Yu et al. 2004). It is highly plausible that vinclozolin can induce such anomalies of the reproductive tract in humans (Kavlock and Cummings 2005). However, most studies used doses 100 times the U.S. Environmental Protection Agency (EPA) no observed adverse effect level (NOAEL) of 1.2 mg/kg body weight/day based on a combination of chronic toxicity, carcinogenicity, and reproductive toxicity in rats (U.S. EPA 2003). To our knowledge, only one recent study has investigated the reproductive consequences (the frequency of hypospadias) of in utero exposure to both genistein and vinclozolin (Vilela et al. 2007). Using a lifelong exposure scheme, we found significant alterations of reproductive development and impairment of several fertility end points by these compounds, the most severe effect resulting from combined exposure to a dietary level of genistein and a level of vinclozolin lower than the U.S. EPA-proposed NOAEL. In addition, we found that mRNA expression profiles in the adult testis are notably and differentially modified according to the exposure protocol. We also describe functional clustering of the genes affected into ontologic families.

Soy, phyto-oestrogens and male reproductive function: a review.

Abstract: There is growing interest in the possible health threat posed by the effects of endocrine disruptors on reproduction. Soy and soy-derived products contain isoflavones that mimic the actions of oestrogens and may exert adverse effects on male fertility. The purpose of this review was to examine the evidence regarding the potential detrimental effects of soy and phyto-oestrogens on male reproductive function and fertility in humans and animals. Overall, there are some indications that phyto-oestrogens, alone or in combination with other endocrine disruptors, may alter reproductive hormones, spermatogenesis, sperm capacitation and fertility. However, these results must be interpreted with care, as a result of the paucity of human studies and as numerous reports did not reveal any adverse effects on male reproductive physiology. Further investigation is needed before a firm conclusion can be drawn. In the meantime, caution would suggest that perinatal phyto-oestrogen exposure, such as that found in infants feeding on soy-based formula, should be avoided.

Sperm parameters and male fertility after bariatric surgery: three case series.

Abstract: Recent studies have underlined the impact of obesity on sperm parameters, but very few data are available on the effect of weight loss on male fertility. This article reports the case series of three male patients who underwent rapid and major weight loss following bariatric surgery and the consequences of this surgery on semen parameters and fertility. A severe worsening of semen parameters was observed during the months after bariatric surgery, including extreme oligoasthenoteratozoospermia, but azoospermia was not observed. This effect may hypothetically be the result of two opposite mechanisms: (i) the suppression of the deleterious effects of obesity; and (ii) the negative impact of both nutritional deficiencies and the release of toxic substances. Information about potential reproductive consequences of bariatric surgery should be given to patients and sperm cryopreservation before surgery proposed. However, for one case, the alterations of spermatogenesis were reversible 2 years after the surgical procedure. Finally, intracytoplasmic sperm injection with fresh spermatozoa after male bariatric surgery can be successful, as demonstrated here, where clinical pregnancies were obtained for two out of the three couples.

Hormones and endocrine-disrupting chemicals: Low-dose effects and nonmonotonic dose responses

Abstract: For decades, studies of endocrine-disrupting chemicals (EDCs) have challenged traditional concepts in toxicology, in particular the dogma of “the dose makes the poison,” because EDCs can have effects at low doses that are not predicted by effects at higher doses. Here, we review two major concepts in EDC studies: low dose and nonmonotonicity. Low-dose effects were defined by the National Toxicology Program as those that occur in the range of human exposures or effects observed at doses below those used for traditional toxicological studies. We review the mechanistic data for low-dose effects and use a weight-of-evidence approach to analyze five examples from the EDC literature. Additionally, we explore nonmonotonic dose-response curves, defined as a nonlinear relationship between dose and effect where the slope of the curve changes sign somewhere within the range of doses examined. We provide a detailed discussion of the mechanisms responsible for generating these phenomena, plus hundreds of examples from...

World Health Organization reference values for human semen characteristics

Abstract: BACKGROUND Semen quality is taken as a surrogate measure of male fecundity in clinical andrology, male fertility, reproductive toxicology, epidemiology and pregnancy risk assessments. Reference intervals for values of semen parameters from a fertile population could provide data from which prognosis of fertility or diagnosis of infertility can be extrapolated. METHODS Semen samples from over 4500 men in 14 countries on four continents were obtained from retrospective and prospective analyses on fertile men, men of unknown fertility status and men selected as normozoospermic. Men whose partners had a time-to-pregnancy (TTP) of < or =12 months were chosen as individuals to provide reference distributions for semen parameters. Distributions were also generated for a population assumed to represent the general population. RESULTS The following one-sided lower reference limits, the fifth centiles (with 95th percent confidence intervals), were generated from men whose partners had TTP < or = 12 months: semen volume, 1.5 ml (1.4-1.7); total sperm number, 39 million per ejaculate (33-46); sperm concentration, 15 million per ml (12-16); vitality, 58% live (55-63); progressive motility, 32% (31-34); total (progressive + non-progressive) motility, 40% (38-42); morphologically normal forms, 4.0% (3.0-4.0). Semen quality of the reference population was superior to that of the men from the general population and normozoospermic men. CONCLUSIONS The data represent sound reference distributions of semen characteristics of fertile men in a number of countries. They provide an appropriate tool in conjunction with clinical data to evaluate a patient's semen quality and prospects for fertility.

Temporal trends in sperm count: a systematic review and meta-regression analysis.

Abstract: BACKGROUND Reported declines in sperm counts remain controversial today and recent trends are unknown. A definitive meta-analysis is critical given the predictive value of sperm count for fertility, morbidity and mortality. OBJECTIVE AND RATIONALE To provide a systematic review and meta-regression analysis of recent trends in sperm counts as measured by sperm concentration (SC) and total sperm count (TSC), and their modification by fertility and geographic group. SEARCH METHODS PubMed/MEDLINE and EMBASE were searched for English language studies of human SC published in 1981-2013. Following a predefined protocol 7518 abstracts were screened and 2510 full articles reporting primary data on SC were reviewed. A total of 244 estimates of SC and TSC from 185 studies of 42 935 men who provided semen samples in 1973-2011 were extracted for meta-regression analysis, as well as information on years of sample collection and covariates [fertility group ('Unselected by fertility' versus 'Fertile'), geographic group ('Western', including North America, Europe Australia and New Zealand versus 'Other', including South America, Asia and Africa), age, ejaculation abstinence time, semen collection method, method of measuring SC and semen volume, exclusion criteria and indicators of completeness of covariate data]. The slopes of SC and TSC were estimated as functions of sample collection year using both simple linear regression and weighted meta-regression models and the latter were adjusted for pre-determined covariates and modification by fertility and geographic group. Assumptions were examined using multiple sensitivity analyses and nonlinear models. OUTCOMES SC declined significantly between 1973 and 2011 (slope in unadjusted simple regression models -0.70 million/ml/year; 95% CI: -0.72 to -0.69; P < 0.001; slope in adjusted meta-regression models = -0.64; -1.06 to -0.22; P = 0.003). The slopes in the meta-regression model were modified by fertility (P for interaction = 0.064) and geographic group (P for interaction = 0.027). There was a significant decline in SC between 1973 and 2011 among Unselected Western (-1.38; -2.02 to -0.74; P < 0.001) and among Fertile Western (-0.68; -1.31 to -0.05; P = 0.033), while no significant trends were seen among Unselected Other and Fertile Other. Among Unselected Western studies, the mean SC declined, on average, 1.4% per year with an overall decline of 52.4% between 1973 and 2011. Trends for TSC and SC were similar, with a steep decline among Unselected Western (-5.33 million/year, -7.56 to -3.11; P < 0.001), corresponding to an average decline in mean TSC of 1.6% per year and overall decline of 59.3%. Results changed minimally in multiple sensitivity analyses, and there was no statistical support for the use of a nonlinear model. In a model restricted to data post-1995, the slope both for SC and TSC among Unselected Western was similar to that for the entire period (-2.06 million/ml, -3.38 to -0.74; P = 0.004 and -8.12 million, -13.73 to -2.51, P = 0.006, respectively). WIDER IMPLICATIONS This comprehensive meta-regression analysis reports a significant decline in sperm counts (as measured by SC and TSC) between 1973 and 2011, driven by a 50-60% decline among men unselected by fertility from North America, Europe, Australia and New Zealand. Because of the significant public health implications of these results, research on the causes of this continuing decline is urgently needed.