From mother to child: investigation of prenatal and postnatal exposure to persistent bioaccumulating toxicants using breast milk and placenta biomonitoring.

The exposure levels of placenta and paired breast milk samples to selected organochlorine compounds and pesticides from Danish and Finnish samples have been investigated. p,p'-DDE is the dominant pollutant, beta-HCH, hexachlorobenzene, endosulfan-I, dieldrin, oxychlordane, cis-heptachlor epoxide and p,p'-DDT being the other major constituents. Their concentrations are linearly correlated between milk and placenta in similar patterns for Danish and Finnish samples. Milk samples have higher levels of these pollutants than placenta on lipid base. However, the apparently not correlated compounds, such as alpha-HCH, pentachlorobenzene, pentachloroanisole and methoxychlor, are generally accumulated more in placenta, which may suggest a tissue specific metabolic activity. Thus, depending on the compound of interest, biomonitoring may be done in placenta only or in both matrices.

Does variant luteinizing hormone (V-LH) predispose to improper testicular position in late pregnancy?

Undescended testes are a common urogenital malformation affecting 2-9% of newborn boys. The etiology of cryptorchidism is probably heterogeneous, but insufficient androgen effect has been recognized as one cause of the condition. A common genetic variant (V) form of LH occurs in apparently healthy individuals universally. Compared with wild-type (WT) LH, the V-LH molecule has increased bioactivity in vitro but shorter half-life in vivo. In the present study, we screened 93 cryptorchid (59 uni- and 34 bilateral) and 211 healthy boys for the occurrence of V-LH to evaluate whether it is related to testicular descent. Two immunofluorometric assays with different combinations of MAb, one detecting WT-LH, the other detecting both WT- and V-LH, were used to measure LH concentrations. The ratio of two LH measurements was used to assess the V-LH status. The prevalence of V-LH was similar in the control and cryptorchid groups, and the total prevalence of V-LH corresponded well to the prevalence of V-LH in general Finnish population. Among cryptorchid boys, the prevalence of V-LH was dependent on gestational age: 6.7% at GA <37, 20.9% at GA 37-39, and 42.9% at GA of 40-42 wk. In contrast, the percentage of V-LH status was similar at different gestational ages in all control groups. We conclude that V-LH is not critical for normal testicular descent but the increased prevalence of V-LH among cryptorchid boys with GA >40, suggests that the lower hormonal efficacy of V-LH predisposes for improper testicular descent in late pregnancy.

Circannual rhythm in the incidence of cryptorchidism in Finland.

Conflicting data on circannual variation in birth rates of urogenital malformations have been reported previously. To assess risk factors of cryptorchidism we studied the seasonal variation of cryptorchidism in Finland. We performed a prospective cryptorchidism study in Turku, Finland, from 1997 to 2001 to evaluate the incidence of cryptorchidism. Clinical examinations were performed at birth and at 3 months. Of 9511 liveborn boys (1471 preterm boys) 216 (53 preterm boys) were cryptorchid at birth and 106 (19 preterm boys) at 3 months. The incidence of cryptorchidism was significantly higher in spring (February-April) (3.0%) than in summer (May-July) (1.7%) (OR 1.79; 95% CI: 1.23-2.63). This seasonal difference was observed both among preterm and term boys. We conclude that a circannual fluctuation in the incidence of cryptorchidism exists, which indicates an influence by environmental factors. The underlying reason for cyclicity affects similarly both preterm and term boys.

Serum androgen bioactivity in cryptorchid and noncryptorchid boys during the postnatal reproductive hormone surge.

The first postnatal months of life in boys are characterized by activation of the hypothalamic-pituitary-testicular axis that results in the well depicted surge of reproductive hormones. Serum testosterone levels at that time are high, but infants do not display signs of virilization, and subsequently there is only indirect evidence that circulating androgens during the surge are biologically active. We used a recombinant cell bioassay to determine serum androgen bioactivity in 80 3-month-old boys born after full-term pregnancies (37-42 wk) in whom localization of the testes was determined by palpation after birth and at a mean age of 3 months. At that age, serum androgen bioactivity ranged from less than 0.8 to 1.9 nM testosterone equivalents and correlated with serum testosterone concentration (r = 0.71; P < 0.0001; n = 34), free androgen index (r = 0.80; P < 0.0001; n = 34), age (r = -0.29; P < 0.01; n = 80), and localization of the testes (r = -0.24; P < 0.05; n = 80). Moreover, all boys in this study with detectable androgen bioactivity (n = 26) had testes located in scrotal or high scrotal position (n = 64), whereas all boys (n = 16) with at least 1 suprascrotal, inguinal, or nonpalpable testis had nonmeasurable androgen bioactivity in serum (P < 0.01). We conclude that 3-month-old boys are exposed to biological effects of androgens during the postnatal activation of the hypothalamic-pituitary-testicular axis, and that this exposure may be reduced in boys with at least 1 testis located superior to the scrotum.

Gender difference in breast tissue size in infancy: correlation with serum estradiol.

Breast tissue in newborn infants is considered to be physiologic and mainly related to exposure to maternal hormones in utero or through breast-feeding. However, controversy exists as to whether breast tissue in later infancy is under the influence of endogenous hormones. Children at 2-4 mo of age have a surge of reproductive hormones, including estradiol, which may affect the mammary gland. In a prospective cohort study of 1126 healthy, 3-mo-old infants, breast tissue size and reproductive hormones were measured. We found that palpable breast tissue (diameter >or=3 mm) is a common physiologic condition present in 78.9% of children, significantly more frequent (p < 0.001) and larger (p < 0.001) in girls than in boys. Girls had significantly higher median estradiol levels than boys (30.0 versus 21.0 pmol/L, p < 0.001). In a multiple regression model including breast tissue size given as quartiles as the dependent variable and weight for gestational age, subscapular skinfold, weight at 3 mo of age and serum estradiol as independent variables, a gender difference was shown. In girls, the estradiol level was positively (p < 0.03) correlated to breast quartile. In boys, no correlations were found. Whether the stimulation of the mammary gland in infancy represents a developmental window that is of biologic significance for breast development and pathology in adulthood remains to be defined.

Changes in male reproductive health and effects of endocrine disruptors in Scandinavian countries

A saúde reprodutiva masculina tem-se deteriorado de diversas maneiras nas últimas décadas. A incidência do câncer de testículo aumentou rapidamente na Europa e nas populações descendentes de europeus. A concentração de espermatozóides tem decaído, e a motilidade e morfologia tem piorado em muitas regiões. Ambas tendências adversas foram correlacionadas ao ano de nascimento. As coortes mais velhas apresentam melhor saúde reprodutiva do que as erações mais jovens. De acordo com vários estudos, as incidências de criptorquidia e de hipospadia vem aumentando. Não se conhecem os fatores envolvidos nessas tendências, mas a velocidade da mudança sugere alterações ambientais. Foi levantada a hipótese da influência dos desreguladores endócrinos sobre a saúde reprodutiva masculina.

Changes in male reproductive health and effects of endocrine disruptors in Scandinavian countries.

Male reproductive health has deteriorated in many ways during the last decades. The incidence of testicular cancer has rapidly increased in Europe and European-derived populations. Sperm concentrations have declined and sperm motility and morphology have worsened in many areas. Both adverse trends have been shown to be associated with year of birth. Older birth cohorts have better reproductive health than the younger generations. Incidences of cryptorchidism and hypospadias have also increased according to several studies. The reasons for secular trends are unknown, but the rapid pace of the change points to environmental causes. Endocrine disrupting chemicals have been hypothesized to influence male reproductive health.