Can maternal postpartum testosterone and estradiol retrospectively predict the offspring's sex at birth? A cross‐sectional study in Ghana

The selection of X‐ or Y‐bearing spermatozoa during fertilization may depend on maternal circulating sex hormones. The zona pellucida of the developing oocyte is adapted to be selective for the Y‐bearing spermatozoa when maternal circulating androgens are relatively high. This study sought to determine whether maternal postpartum testosterone and estradiol can retrospectively predict the offspring sex at birth. The study was cross‐sectional from December 2020 to April 2021 at the Reproductive and Child Health unit in Tamale. The participants were part of a previous study and comprised 178 mother–offspring dyads (mother–daughter = 90, mother–son = 88). The mothers were between the ages of 18 and 35 years and had a median (interquartile range‐IQR) postpartum interval of 111 (60–187) days. A single venous blood sample was drawn from the mothers between 8.00 am and 12.00 pm local time on each day to reduce diurnal variation. Postpartum serum estradiol, testosterone, and sex hormone‐binding globulin were assayed using the ELISA technique. The serum total testosterone and the testosterone‐to‐estradiol ratio (TT: E2) were higher in mothers with sons while estradiol was higher in mothers with daughters (p < 0.050). The total testosterone and TT: E2 did not markedly differ by their area under the curve (AUC: 0.91 and 0.99, respectively) but both were higher than the AUC of estradiol (0.72). The Sensitivity was 97.7%, 97.7%, and 94.5% and specificity, 88.9%, 40.0%, and 95.5% at cutoff points of >1.659 nmol/L, ≤141.862 pmol/L, and > 31.5, respectively for total testosterone, estradiol, and TT: E2. The maternal testosterone‐to‐estradiol ratio may be more predictive of offspring sex at birth than either testosterone or estradiol alone.

[1]  N. Amidu,et al.  The association between the 2D:4D ratio and offspring sex at birth: A cross‐sectional study in Ghana , 2022, American journal of human biology : the official journal of the Human Biology Council.

[2]  N. Amidu,et al.  The relationship between 2D:4D ratio and postpartum adult female variables in a Ghanaian population , 2021, American journal of human biology : the official journal of the Human Biology Council.

[3]  N. Amidu,et al.  Second to fourth (2D:4D) digit ratio and their relationships among a mother and child population in Ghana , 2021, Scientific Reports.

[4]  S. Swan,et al.  Digit ratio, a proposed marker of the prenatal hormone environment, is not associated with prenatal sex steroids, anogenital distance, or gender-typed play behavior in preschool age children , 2020, Journal of Developmental Origins of Health and Disease.

[5]  J. Flegr,et al.  The effects of toxoplasmosis on sex ratio at birth. , 2020, Early human development.

[6]  P. Urbanová,et al.  Family effects on the digit ratio (2D:4D): The role of the interbirth interval , 2019, American journal of human biology : the official journal of the Human Biology Council.

[7]  P. Ranganathan,et al.  Understanding the properties of diagnostic tests – Part 2: Likelihood ratios , 2018, Perspectives in clinical research.

[8]  E. Cameron,et al.  Developmental sexual dimorphism and the evolution of mechanisms for adjustment of sex ratios in mammals , 2017, Annals of the New York Academy of Sciences.

[9]  W. James Proximate causes of the variation of the human sex ratio at birth. , 2015, Early human development.

[10]  J. Pennings,et al.  Diurnal Variation of Hormonal and Lipid Biomarkers in a Molecular Epidemiology-Like Setting , 2015, PloS one.

[11]  C. Alminana-Brines Snooping on a private conversation between the oviduct and gametes/embryos , 2015 .

[12]  G. Nabi,et al.  Effect of Fetal Sex on Total Levels of Maternal Serum Testosterone , 2014 .

[13]  T. Ventura,et al.  Digit ratio (2D:4D) in newborns: influences of prenatal testosterone and maternal environment. , 2013, Early human development.

[14]  M. Cohn,et al.  Developmental basis of sexually dimorphic digit ratios , 2011, Proceedings of the National Academy of Sciences.

[15]  A. Gutiérrez-Adán,et al.  Intrafollicular testosterone concentration and sex ratio in individually cultured bovine embryos. , 2010, Reproduction, fertility, and development.

[16]  M. Beckett,et al.  Mechanisms by which circadian rhythm disruption may lead to cancer , 2010 .

[17]  W. James FURTHER SUPPORT FOR THE HYPOTHESIS THAT PARENTAL HORMONE LEVELS AROUND THE TIME OF CONCEPTION ARE ASSOCIATED WITH HUMAN SEX RATIOS AT BIRTH , 2008, Journal of Biosocial Science.

[18]  A. Shelling,et al.  Sex of bovine embryos may be related to mothers' preovulatory follicular testosterone. , 2008, Biology of reproduction.

[19]  A. Akobeng,et al.  Understanding diagnostic tests 3: receiver operating characteristic curves , 2007, Acta paediatrica.

[20]  N. Cook Use and Misuse of the Receiver Operating Characteristic Curve in Risk Prediction , 2007, Circulation.

[21]  J. Flegr,et al.  Women infected with parasite Toxoplasma have more sons , 2007, Naturwissenschaften.

[22]  R. Catalano,et al.  Secondary sex ratios and male lifespan: Damaged or culled cohorts , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[23]  N. Saino,et al.  Human digit ratios depend on birth order and sex of older siblings and predict maternal fecundity , 2006, Behavioral Ecology and Sociobiology.

[24]  C. Redi,et al.  Experimental demonstration that mammalian oocytes are not selective towards X‐ or Y‐bearing sperm , 2005, Molecular reproduction and development.

[25]  E. Cameron Facultative adjustment of mammalian sex ratios in support of the Trivers–Willard hypothesis: evidence for a mechanism , 2004, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[26]  W. James Further evidence that mammalian sex ratios at birth are partially controlled by parental hormone levels around the time of conception. , 2004, Human reproduction.

[27]  John Attia,et al.  Moving beyond sensitivity and specificity: using likelihood ratios to help interpret diagnostic tests , 2003 .

[28]  D. Panidis,et al.  Effect of the interval between pregnancies on the health of mother and child. , 2002, European journal of obstetrics, gynecology, and reproductive biology.

[29]  R. Trivers,et al.  2nd to 4th digit ratio and offspring sex ratio. , 2002, Journal of theoretical biology.

[30]  A. Vermeulen,et al.  A critical evaluation of simple methods for the estimation of free testosterone in serum. , 1999, The Journal of clinical endocrinology and metabolism.

[31]  Kevin Chu,et al.  An introduction to sensitivity, specificity, predictive values and likelihood ratios , 1999 .

[32]  W. James Hypotheses on mammalian sex ratio variation at birth. , 1998, Journal of theoretical biology.

[33]  V. J. Grant,et al.  Sex determination and the maternal dominance hypothesis. , 1996, Human reproduction.

[34]  S. Krackow The developmental asynchrony hypothesis for sex ratio manipulation. , 1995, Journal of theoretical biology.

[35]  L. Liang,et al.  Coordinate expression of the three zona pellucida genes during mouse oogenesis. , 1995, Development.

[36]  J. Hanley,et al.  Statistical Approaches to the Analysis of Receiver Operating Characteristic (ROC) Curves , 1984, Medical decision making : an international journal of the Society for Medical Decision Making.

[37]  T. Bäckström,et al.  Calculation of free and bound fractions of testosterone and estradiol-17 beta to human plasma proteins at body temperature. , 1982, Journal of steroid biochemistry.

[38]  Dan E. Willard,et al.  Natural Selection of Parental Ability to Vary the Sex Ratio of Offspring , 1973, Science.

[39]  Yisroel Cofsky The Science Journal of the Lander College of Arts and Sciences The Science Journal of the Lander College of Arts and Sciences Current Theories on the Human Sex Ratio Current Theories on the Human Sex Ratio , 2020 .

[40]  L. M. Thurston,et al.  Battle of the Sexes: How the Selection of Spermatozoa in the Female Reproductive Tract Manipulates the Sex Ratio of Offspring , 2017 .

[41]  W. Holt,et al.  Sperm selection in the female mammalian reproductive tract. Focus on the oviduct: Hypotheses, mechanisms, and new opportunities. , 2016, Theriogenology.

[42]  B. Gadella,et al.  Membrane fusions during mammalian fertilization. , 2011, Advances in experimental medicine and biology.