Insulin-like factor 3 levels in amniotic fluid of human male fetuses

Anand‐Ivell, Ravinder; Ivell, Richard; Driscoll, Deborah A.; Manson, Jeanne M.

doi:10.1093/humrep/den038

Cited by 60 publications

(49 citation statements)

References 36 publications

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“…Transcripts encoding the critical enzymes required for androgen production can be detected in the testis shortly after Leydig cell differentiation (13.0 dpc in the mouse and 35 dpc in the sheep; Greco & Payne 1994, Quirke et al 2001, and testosterone can be detected at around 13.0 dpc in the mouse (Gondos 1980), 35 dpc in the sheep (Quirke et al 2001), and at 7 GW in the human, peaking in the human in the early second trimester (Tapanainen et al 1981, Fowler et al 2009, Scott et al 2009). INSL3 production by the fetal Leydig cells appears to be largely constitutive, and Insl3 transcripts are detectable in the mouse testis at about the same time as Leydig cell differentiation in the mouse (McKinnell et al 2005), and both INSL3 protein and transcript are clearly present in the male human fetus by the early second trimester (Anand-Ivell et al 2008, Bay et al 2008.…”

Section: Fetal Testicular Hormone Productionmentioning

confidence: 96%

Endocrinology of the mammalian fetal testis

O’Shaughnessy¹,

Fowler²

2011

Reproduction

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The testes are essential endocrine regulators of fetal masculinization and male development and are, themselves, subject to hormonal regulation during gestation. This review focuses, primarily, on this latter control of testicular function. Data available suggest that, in most mammalian species, the testis goes through a period of independent function before the fetal hypothalamic-pituitary-gonadal axis develops at around 50% of gestation. This pituitary-independent phase coincides with the most critical period of fetal masculinization. Thereafter, the fetal testes appear to become pituitary hormone-dependent, concurrent with declining Leydig cell function, but increasing Sertoli cell numbers. The two orders of mammals most commonly used for these types of studies (rodents and primates) appear to represent special cases within this general hypothesis. In terms of testicular function, rodents are born 'early' before the pituitary-dependent phase of fetal development, while the primate testis is dependent upon placental gonadotropin released during the pituitary-independent phase of development.

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Section: Fetal Testicular Hormone Productionmentioning

confidence: 96%

Endocrinology of the mammalian fetal testis

O’Shaughnessy¹,

Fowler²

2011

Reproduction

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“…Moreover, of the endogenous hormones being produced by the fetus in measurable amounts, few have the required specificity to be able to offer any conclusive diagnostic outcome. So, for example, androgens are generated by both adrenal glands and gonads at this time, and thus are expressed by both male and female fetuses in not very different amounts (Anand-Ivell et al 2008, Scott et al 2009). An exception is provided by the small peptide hormone INSL3, which is produced in large amounts by the fetal testis shortly after sex determination (Anand-Ivell et al 2008).…”

Section: Introductionmentioning

confidence: 96%

“…So, for example, androgens are generated by both adrenal glands and gonads at this time, and thus are expressed by both male and female fetuses in not very different amounts (Anand-Ivell et al 2008, Scott et al 2009). An exception is provided by the small peptide hormone INSL3, which is produced in large amounts by the fetal testis shortly after sex determination (Anand-Ivell et al 2008). It is produced by no other fetal organ, consequently does not appear to be produced by the female fetus (Anand-Ivell et al 2008, Bay et al 2008, and is made in only very low amounts by the maternal ovary .…”

Section: Introductionmentioning

confidence: 96%

“…An exception is provided by the small peptide hormone INSL3, which is produced in large amounts by the fetal testis shortly after sex determination (Anand-Ivell et al 2008). It is produced by no other fetal organ, consequently does not appear to be produced by the female fetus (Anand-Ivell et al 2008, Bay et al 2008, and is made in only very low amounts by the maternal ovary . It thus has the potential to be a highly specific monitor for any events impacting on the normal differentiation and development of the fetal testis during the important window for endocrine disruption at the transition from first to second trimesters (in the human).…”

Section: Introductionmentioning

confidence: 99%

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Insulin-like factor 3 as a monitor of endocrine disruption

Anand‐Ivell

Ivell

2014

Reproduction

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Insulin-like factor 3 (INSL3) is generated and secreted by differentiated interstitial Leydig cells of the testes in both fetal and adult males of all mammalian species so far analyzed. All evidence to date suggests that it is produced constitutively, independently of acute regulation by the hypothalamo-pituitary-gonadal (HPG) axis, in amounts which reflect the numbers and differentiation status of the Leydig cells. This Leydig cell functional capacity is otherwise monitored only by androgen output, which, however, is massively confounded by acute regulation from the HPG axis and other factors leading to substantial and irregular short-term variation. Leydig cells are a primary target of endocrine-disrupting agents in the context of the testicular dysgenesis syndrome in the fetal male, as well as in the adult. In the male fetus, INSL3 is responsible for the first phase of testicular descent, and hence is directly linked to the etiology of cryptorchidism. In this study, by measuring INSL3 production, for example, during fetal life via amniotic fluid, or as secretions from fetal testis explants, or in adult peripheral blood, we and others have shown that INSL3 represents a useful quantitative and sensitive endpoint for assessing the impact of endocrine-disrupting agents and their mechanisms of action.Reproduction (2014) 147 R87-R95

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“…Total testosterone was measured using a well validated in-house time-resolved fluorescent immunoassay following cold ethanol extraction. 20 INSL3 in blood was measured using a rodent-specific time-resolved fluorescent immunoassay, exactly as previously described. 21 Luteinising hormone (LH) was estimated using a commercial rat LH ELISA kit (USCN Life, Wuhan, China), according to the manufacturer's protocol.…”

Section: Immunoassaysmentioning

confidence: 99%

Brief maternal exposure of rats to the xenobiotics dibutyl phthalate or diethylstilbestrol alters adult-type Leydig cell development in male offspring

Ivell¹,

Heng²,

Nicholson³

et al. 2013

Asian J Androl

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Maternal exposure to estrogenic xenobiotics or phthalates has been implicated in the distortion of early male reproductive development, referred to in humans as the testicular dysgenesis syndrome. It is not known, however, whether such early gestational and/or lactational exposure can influence the later adult-type Leydig cell phenotype. In this study, Sprague-Dawley rats were exposed to dibutyl phthalate (DBP; from gestational day (GD) 14.5 to postnatal day (PND) 6) or diethylstilbestrol (DES; from GD14.5 to GD16.5) during a short gestational/lactational window, and male offspring subsequently analysed for various postnatal testicular parameters. All offspring remained in good health throughout the study. Maternal xenobiotic treatment appeared to modify specific Leydig cell gene expression in male offspring, particularly during the dynamic phase of mid-puberty, with serum INSL3 concentrations showing that these compounds led to a faster attainment of peak values, and a modest acceleration of the pubertal trajectory. Part of this effect appeared to be due to a treatment-specific impact on Leydig cell proliferation during puberty for both xenobiotics. Taken together, these results support the notion that maternal exposure to certain xenobiotics can also influence the development of the adult-type Leydig cell population, possibly through an effect on the Leydig stem cell population.

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Insulin-like factor 3 levels in amniotic fluid of human male fetuses

Abstract: INSL3 concentration in human amniotic fluid is potentially predictive of fetal sex and pre-eclampsia, and presumably reflects the functioning of the fetal Leydig cell population.

Cited by 60 publications

References 36 publications

Endocrinology of the mammalian fetal testis

Endocrinology of the mammalian fetal testis

Insulin-like factor 3 as a monitor of endocrine disruption

Brief maternal exposure of rats to the xenobiotics dibutyl phthalate or diethylstilbestrol alters adult-type Leydig cell development in male offspring

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