Gavino Faa (Cagliari), Salvatore Vendemmia (Aversa), Vassilios Fanos (Cagliari)
Since the placenta originates from the fertilized egg, the sex of the fetus (XY or XX) represents an important factor when dealing with placenta, both in physiology and in pathology. The genetic sex of the fertilized egg matches the placenta’s genetics: as a consequence, female and male placentas may differ in gene expression, structure and function, with possible relevant consequences on fetal growth and in managing stress conditions during gestation (1)
Gender-related differences in fetal developments have been reported in the recent literature. Female babies are much more resilient than boys and have better outcomes from maternity complications. On the contrary, male baby pregnancies are more likely to result in complications, possibly because they grow faster in the womb and require more nutrients and oxygen than supplied by the placenta – the temporary organ deputed to help the fetal growth and development (2). Male fetuses are more likely to be delivered prematurely, and the death rate is higher for male than for female fetuses (3).
A growing body of evidence highlited, in recent years, the key role of gender-differences in pregnancy outcome, showing that the survival skills of girl babies are facilitated by the nourishment they receive from a female placenta (4). Marked differences have been also reported regarding the mechanims that drive male- and female-specific intrauterine fetal growth and development (5). One of the key differences between how male and female babies grow in the womb is that male fetuses prioritize size during gestation (2). Starting from conception, male embryos grow faster than females, and by the time of birth the average male weight is higher than the average female birthweight (6).
But the price that boys pay for this evolutionary emphasis on size is that they are less able to adapt to environmental stress. Male babies are more likely to be spontaneously aborted or born premature (3). Moreover, the impact of gestational hypertension and preeclampsia on pregnacy outcome is higher in male fetuses as compared with females (7).
A meta-analysis on the role of fetal and placental sex on pregnancy outcome, confirmed that male fetal (and placental) sex is associated with term pre-eclampsia and gestational diabetes , highlighting that all other pregnancy complications, including gestational hypertension, total pre-eclampsia, eclampsia, placental abruption, and post-partum hemorrhage, are associated with male (and placental) fetal sex (8).
Female placentas are generally considered to do a better job in managing stress conditions occurring in utero, thanks to chromosome-linked gene expression. Studies of male versus female placentas from full-term pregnancies have revealed widespread differences in hormone signaling, immune signaling, and metabolic placental functions (4). Furthermore, male and female placentas have been proposed to drive differently fetal growth during gestation, ending with different developmental outcomes (5).
The differences in function between male and female placentas might be related to sex differentiated placental methylation, that could influence the regulation of gene expression. This significant difference in gene expression might have implications for fetal development during gestation, and could influence the susceptibility to the insurgence of multiple diseases of the newborn later in life, according with the Barker’s hypothesis on fetal programming of adult diseases (9,10).
In conclusion, whereas placenta has been for a long time considered the same entity, irrespectively of fetal gender and consequently of placental gender, in recent years multiple scientific evidences revealed that male and female placentas represent two different organs, with differences in secretion of hormones and immune factors (11). The placenta of one sex over the other possesses greater ability to respond and buffer against the environmental insults that may occur during gestation (4). Furthermore, sex-related structural differences have been found in human placenta, chorionic plate of females being larger as compared with male placentas (12). Female placentas are characterized by their higher resilience and by a higher adaptability to stress conditions, qualities that surely contribute to a more favorable outcome of female gestations. On the other hand, male placentas are designed to prioritize a rapid fetal growth, but they are more vulnerable to stress conditions occurring in the intrauterine life, ending with the higher incidence of placental complications and preterm delivery in males.
All these findings taken together underline the major role of placental sex in fetal development. Further studies are needed to better analyze histopathological features of male and female placentas, towards a better knowledge of the gender-related structural differences in female and male placentas, possibly identifying sex-related differences in the placental-fetal immunotolerance, a key factor in pregnancy outcome.
References
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