Gaspari L, Sampaio DR, Paris F, Audran F, Orsini M, Neto JB, Sultan C.

DOI:10.3410/f.717973543.793470158

Abstract 

Exposure to endocrine-disrupting chemicals (EDCs) has been suggested to contribute to the increasing trends of external genital malformation in male newborns. In Northeastern Brazil, the poor sanitary conditions found in the favelas encourage the widespread use of pesticides. This 2-year study of a total birth cohort of full-term male newborns in the regional hospitals of Campina Grande (Paraíba, Brazil) sought to (1) accurately establish for the first time the incidences of neonatal male genital malformations, (2) investigate the endocrine and genetic aetiologies of these malformations, and (3) evaluate their associations with possible prenatal exposure to EDCs. A total of 2710 male newborns were explored for cryptorchidism, hypospadias and micropenis. Cases were referred to the Pediatric Endocrine Clinic for endocrine and genetic investigations, and all parents were interviewed about their environmental/occupational exposure to EDCs before/during pregnancy by paediatric endocrinologists using a detailed questionnaire. We observed 56 cases of genital malformation (2.07%), including 23 cryptorchidism (0.85%), 15 hypospadias (0.55%), and 18 micropenis (0.66%). All cases exhibited normal/subnormal testosterone production and none presented androgen receptor or 5α-reductase gene mutation. More than 92% of these newborns presented foetal contamination by EDCs, as their mothers reported daily domestic use of pesticides (i.e., DDT) and other EDCs. Most of these undervirilized male newborns presented additional EDC contamination, as 80.36% of the mothers and 58.63% of the fathers reported paid or unpaid work that entailed the use of pesticides and other EDCs before/during pregnancy for the mothers and around the time of fertilization for the fathers. The high rate of micropenis in our population associated with an elevated percentage of parental environmental/occupational exposure to EDCs before/during pregnancy indicates that foetal contamination may be a risk factor for the development of male external genital malformation.  

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Summary 

In this study, noteworthy for its shortcomings as much as for what it achieves, all boys (n=2710) born during a two-year period in the regional hospitals of Campina Grande were assessed for neonatal genital malformations. Those who exhibited cryptorchidism, hypospadias or micropenis were referred for endocrine and genetic work-ups, and endocrine-disrupting chemical (EDC) exposure was assessed through interviews with a questionnaire. Data on genital anomaly prevalence were compared with prevalence data from other studies.

The stated purpose of this study was to “determine whether foetal exposure to EDCs plays a potential role in the development of abnormal male external genitalia in one of the poorest and most polluted regions in Brazil, where heavy pesticide use is common”. The specific objectives of the study were threefold: (a) to establish incidences of male genetic malformations, (b) to investigate the endocrine and genetic etiologies of those malformations, and (c) to investigate prenatal exposure to EDCs through assessing parental exposure. The authors have met the first two objectives in establishing incidences of cryptorchidism, hypospadias and micropenis in full-term male newborns in the Campina Grande regional hospitals, Brazil, and investigated affected infants for underlying endocrine or genetic causes. Unfortunately, the third objective was not met. Although Gaspari and colleagues pose an important research question about the role of EDCs in male genital abnormalities, the limitations of their study design preclude reaching any conclusion about the question.

First, information regarding EDC exposure of parents was obtained only for those with sons born with atypical genitalia. Without comparable exposure data for parents of physically typical sons, it is not possible to draw any conclusions regarding associations. Second, the paper provides no information about interviewer training, interview protocol, reliability or validity, or content of the parent questionnaire. Regardless of whether parents worked directly with EDCs, general environmental exposure would likely be high in the favelas (shanty towns) of Campina Grande due to the close quarters and heavy usage of (often illegal) pesticides. Use of agent-specific biomarkers to measure exposure would be more accurate and, in addition to the questionnaire, could contribute to the development of a validated questionnaire to estimate EDC exposure. Measures of total effective xenoestrogen burden have been taken from placental samples {1}. EDC levels could also be assessed in pregnant mothers during the period of foetal penile formation and growth. Third, the micropenis prevalence data for comparison is limited to three other studies employing ethnically diverse samples and different definitions of micropenis. Due to the relatively low incidence of micropenis, the rates may be quite unstable, in particular given the likelihood of measurement error.

This study makes two main contributions to the literature. First, incidences of cryptorchidism, hypospadias, and micropenis are established for a two-year birth cohort in Campina Grande, Brazil. Second, rates for hypospadias and cryptorchidism were concordant with those reported for a large number of studies conducted internationally. The study does not, however, demonstrate the link between EDCs and micropenis implied by the title.

References  

1.Human exposure to endocrine-disrupting chemicals and prenatal risk factors for cryptorchidism and hypospadias: a nested case-control study.
Fernandez MF, Olmos B, Granada A, López-Espinosa MJ, Molina-Molina JM, Fernandez JM, Cruz M, Olea-Serrano F, Olea N. Environ Health Perspect 2007 Dec; 115 Suppl 1:8-14
PMID: 18174944 DOI: 10.1289/ehp.9351

Recommendation Citation 

Sandberg D, Boyse K and Hawver M: F1000Prime Recommendation of [Gaspari L et al., Int J Androl 2012, 35(3):253-64]. In F1000Prime, 15 Mar 2013; DOI: 10.3410/f.717973543.793470158. F1000Prime.com/717973543#eval793470158