Thyroid Hormone Status in Umbilical Cord Serum Is Positively Associated with Male Anogenital Distance

Liu, Rongju; Xu, Xijin; Zhang, Yuling; Zheng, Xuejun; Kim, Stephani S.; Dietrich, Kim N.; Ho, Shuk‐Mei; Reponen, Tiina; Chen, Aimin; Huo, Xia

doi:10.1210/jc.2015-3872

Cited by 11 publications

(14 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(2012a) found a positive association between AGD and serum testosterone levels in men attending an andrology clinic. In a study of male newborns in China, the AGD was associated with increased levels of thyroid hormones in cord serum (Liu et al ., ). We found no significant association between AGD and serum hormone levels, possibly due to the relatively small number of boys for whom hormone data were available (187 of 279), especially among those in Tanner stage >G1 (28 of 57 boys).…”

Section: Discussionmentioning

confidence: 97%

“…Thus, several studies in groups of volunteers or men attending andrology clinics have published evidence linking shorter AGD with worse sperm quality (Mendiola et al ., , ; Eisenberg & Lipshultz, ), reduced fertility (Eisenberg et al ., ), azoospermia (Eisenberg et al ., 2012b), and lower testosterone and estradiol levels (Eisenberg et al ., 2012a; Zhou et al ., ). In adults, a shorter AGD has been also related to the risk of prostate cancer (Castaño‐Vinyals et al ., ), while in male human fetuses, newborns, and infants, it has been associated with hypospadias, cryptorchidism, micropenis, and reduced thyroid hormone levels (Hsieh et al ., , ; Jain & Singal, ; Thankamony et al ., ; Liu et al ., ; Gilboa et al ., ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Anogenital distance and reproductive outcomes in 9‐ to 11‐year‐old boys: the INMA‐Granada cohort study

et al. 2018

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Anogenital distance and reproductive outcomes in 9‐ to 11‐year‐old boys: the INMA‐Granada cohort study

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Low thyroid hormone levels are associated with fetal growth restriction, and there are low circulating total and free thyroid hormones in growth-restricted fetuses (30,45), although there was an insufficient sample to measure thyroid hormone levels in this study. However, free thyroxine and triiodothyronine are not different in cord blood between male and female fetuses (31,48). Whether female and male fetal cardiomyocytes differently express thyroid hormone receptors or critical downstream signaling components remain to be determined.…”

Section: Discussionmentioning

confidence: 98%

Cardiac myocyte proliferation and maturation near term is inhibited by early gestation maternal testosterone exposure

Jonker

Louey

Roselli

2018

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Polycystic ovary syndrome (PCOS) is a complex and common disorder in women, and those affected experience an increased burden of cardiovascular disease. It is an intergenerational syndrome, as affected women with high androgen levels during pregnancy "program" fetal development, leading to a similar phenotype in their female offspring. The effect of excess maternal testosterone exposure on fetal cardiomyocyte growth and maturation is unknown. METHODS Pregnant ewes received biweekly injections of vehicle (Control) or 100 mg testosterone propionate between 30-59 days of gestation (dGA; Early T) or 60-90 dGA (Late T). Fetuses were delivered at ~135 dGA and their hearts enzymatically dissociated to measure cardiomyocyte growth (dimensional measurements), maturation (proportion binucleate), and proliferation (nuclear Ki-67 protein). RESULTS Early T depressed serum insulin-like growth factor 1 (IGF-1) and caused intrauterine growth restriction (IUGR)(P<0.0005). Hearts were smaller in Early T (P<0.001) due to reduced cardiac myocyte maturation (P<0.0005) and proliferation (P=0.017). Maturation was also less in males than in females (P=0.004), independent of treatment. Late T did not affect cardiac growth. CONCLUSIONS Early excess maternal testosterone exposure depresses circulating IGF-1 near term and causes IUGR in both female and male offspring. These fetuses have small, immature hearts with reduced proliferation, which may reduce cardiac myocyte endowment and predispose to adverse cardiac growth in postnatal life. While excess maternal testosterone exposure leads to PCOS and cardiovascular disease in female offspring, it may also predispose to complications of IUGR and cardiovascular disease in male offspring.

show abstract

“…Only one human study has assessed the effects of FT 3 , FT 4 , and TSH concentrations in cord serum on AGD at birth (18). In female newborns, the overall patterns of association between higher FT 3 and FT 4 and shorter AGD were observed in both our study and the study by Liu et al (18), although the association was not statistically significant in the study by Liu et al These differences are likely due to different neonatal TH concentrations (mean comparison: 1.82 vs. 1.63 for FT 3 ; 14.22 vs. 15.61 for FT 4 ). The concentrations of THs in the previous study were measured in cord serum and not in cord plasma, and the laboratory method used was also different (18).…”

Section: Discussionmentioning

confidence: 99%

“…Shorter AGD has been found to be associated with poor sperm quality ( 15 ), infertility ( 16 ), and lower testosterone concentrations ( 16 ) in men and associated with increased risk of endometriomas and deep infiltrating endometriosis in women ( 17 ). To date, only one human study has assessed the associations of thyroid stimulating hormone (TSH), free triiodothyronine (FT 3 ), and free thyroxine (FT 4 ) concentrations in umbilical cord serum with AGD at birth ( 18 ), indicating that thyroid function may be involved in male gonadal development in early life stages. However, its longitudinal effects at a later age are unknown.…”

Section: Introductionmentioning

confidence: 99%

Association Between Neonatal Thyroid Function and Anogenital Distance from Birth to 48 Months of Age

et al. 2021

Self Cite

View full text Add to dashboard Cite

BackgroundEvidence from animal studies has indicated that neonatal thyroid function is vital for the reproductive development. Anogenital distance (AGD), a sensitive biomarker of the fetal hormonal milieu, can be used to predict adult reproductive disorders. However, few human studies have examined the association between neonatal thyroid function and AGD. We aimed to explore their associations in a birth cohort study.MethodsConcentrations of thyroid stimulating hormone (TSH) and thyroid hormones (THs), including total triiodothyronine (TT3), total thyroxine (TT4), free triiodothyronine (FT3), and free thyroxine (FT4) were measured in cord plasma in the Shanghai-Minhang Birth Cohort. The offspring AGD (AGDAP [anus–penis] and AGDAS [anus–scrotum] for boys and AGDAC [anus–clitoris] and AGDAF [anus–fourchette] for girls), body weight and anogenital index (AGI = AGD/weight [mm/kg]) were obtained at each follow-up visit. In total, 344 children (194 boys and 150 girls) with cord plasma concentrations of THs and TSH and at least one AGD measurement at birth and at 6, 12, and 48 months of age were included. Multiple linear regression and generalized estimating equation (GEE) models were used to examine the associations of cord plasma concentrations of THs and TSH with AGI.ResultsMultiple linear regression models showed inverse associations of TT4, FT3, and FT4 with female AGI, although statistical significance was only reached at birth, 6 and 48 months of age. These associations were also found in GEE models: higher TT4 and FT4 concentrations were associated with lower AGIAC (TT4: β = -0.27, 95% CI: -0.50, -0.03 for middle vs. lowest tertile; FT4: β = -0.38, 95% CI: -0.61, -0.16 for middle and β = -0.30, 95% CI: -0.55, -0.04 for highest vs. lowest tertile). Besides, girls with the highest tertile of FT3 concentrations had lower AGIAF than those with the lowest tertile (the highest vs. lowest tertile: β = -0.22, 95% CI: -0.36, -0.08). Positive associations between TSH and AGI at birth and at 12 months of age were observed in boys.ConclusionsThis study provides further evidence on the effects of neonatal thyroid function on reproductive development at an early life stage.

show abstract

Thyroid Hormone Status in Umbilical Cord Serum Is Positively Associated with Male Anogenital Distance

Abstract: In the absence of overt thyroid dysfunction, THs are positively associated with AGD in male newborns. TH effects on body size and head circumference may be modified by maternal secondhand smoke exposure.

Cited by 11 publications

References 39 publications

Anogenital distance and reproductive outcomes in 9‐ to 11‐year‐old boys: the INMA‐Granada cohort study

Anogenital distance and reproductive outcomes in 9‐ to 11‐year‐old boys: the INMA‐Granada cohort study

Cardiac myocyte proliferation and maturation near term is inhibited by early gestation maternal testosterone exposure

Association Between Neonatal Thyroid Function and Anogenital Distance from Birth to 48 Months of Age

Contact Info

Product

Resources

About