Fetal sex differences in human chorionic gonadotropin fluctuate by maternal race, age, weight and by gestational age

Abstract

Circulating levels of the placental glycoprotein hormone human chorionic gonadotropin (hCG) are higher in women carrying female v. male fetuses; yet, the significance of this difference with respect to maternal factors, environmental exposures and neonatal outcomes is unknown. As a first step in evaluating the biologic and clinical significance of sex differences in hCG, we conducted a population-level analysis to assess its stability across subgroups. Subjects were women carrying singleton pregnancies who participated in prenatal and newborn screening programs in CA from 2009 to 2012 (1.1 million serum samples). hCG was measured in the first and second trimesters and fetal sex was determined from the neonatal record. Multivariate linear models were used to estimate hCG means in women carrying female and male fetuses. We report fluctuations in the ratios of female to male hCG by maternal factors and by gestational age. hCG was higher in the case of a female fetus by 11 and 8% in the first and second trimesters, respectively (P <0.0001). There were small (1–5%) fluctuations in the sex difference by maternal race, weight and age. The female-to-male ratio in hCG decreased from 17 to 2% in the first trimester, and then increased from 2 to 19% in the second trimester (P <0.0001). We demonstrate within a well enumerated, diverse US population that the sex difference in hCG overall is stable. Small fluctuations within population subgroups may be relevant to environmental and physiologic effects on the placenta and can be probed further using these types of data.

An Investigation of the Single and Combined Phthalate Metabolite Effects on Human Chorionic Gonadotropin Expression in Placental Cells

“…Sex and gestational variation in hCG have been previously established at the population level in analyses of hCG biomarker data ( Adibi et al 2015b ; Bremme and Eneroth 1983 ; Buckberry et al 2014 ; Clements et al 1976 ; Cowans et al 2009 ; Nagy et al 1994a , 1994b ; Steier et al 1999 ; Yaron et al 2002a ). This type of variation is generally not considered when analyzing in vitro experimental data.…”

Comparison of uterine fibroids’ growth pattern during pregnancy according to fetal sex: an observational study

“…Yaron et al reported that in patients who underwent to ART procedures, from the 14th and the 20th day post-fertilization, women attending a female fetus had higher levels of hCG than women attending a male ( p < 0.002) [10]. Adibi et al also found a significantly higher hCG level ( p < 0.0001) in patients with a female fetus rather than patients with a male fetus both during the first and the second trimester on a wide population (1.1 million) of women subjected to screening [11]. The results of our study are mostly in line with those reports, and, more specifically, we did not find any difference in hCG serum levels until the seventh week of pregnancy, but the values of female fetuses were significantly higher between 11 and 13 gestational weeks.…”

“…One of the factors that most influences the bio-humoral condition of the first weeks of pregnancy seem to be the fetal sex and, specifically, women with female fetus may present higher values of hCG compared to male fetuses [10, 11].…”

The Density of Cell Nuclei at the Materno-Fetal Exchange Barrier is Sexually Dimorphic in Normal Placentas, but not in IUGR

“…During gestation, the biochemical indicators in maternal serum that show fetal/placental sex-dependent variation in concentrations include human chorionic gonadotropin (hCG) 26 , soluble fms-like tyrosine kinase-1 (sFlt-1) 27 and placental alkaline phosphatase (PLAP) 28 . These placental proteins and angiogenic factors show elevated levels in maternal serum of healthy female pregnancies compared to male pregnancies.…”

“…From gene expression studies it is known that the tissues of the placentas do have tissue specific sexually different gene expression patterns (“sexomes”) 33 . Spotting the site of sexual dimorphism is thus essential to reliably connect the genetic 16 , biochemical (placental proteins) 26–28 and gross morphological (placental weight and birthweight) 17,18 sex-specific differences of human placentas to a functional picture by anchoring them to a structure/tissue.…”