Placental function, neurodevelopment and autism likelihood

Autism is diagnosed in males more often than in females, even after accounting for postnatal social factors, such as underdiagnosis, misdiagnosis, camouflaging and masking in females. This suggests that biological factors contribute to sex differences in autism likelihood.   Several lines of evidence support the case that prenatal sex steroid synthesis is altered in pregnancies that result in a later autism diagnosis. Mothers of autistic children also have significantly elevated rates of conditions and pregnancy complications linked to the endocrine system (e.g. polycystic ovary syndrome and gestational diabetes). However, the potential causes of prenatal endocrine disruption and their effects on brain development, remain unclear.   The placenta may be of particular significance in neurodevelopment, as it maintains endocrine homeostasis prenatally and regulates nutrient transfer to the fetus. Placental function is also sexually dimorphic, with placentas of male fetuses producing more steroid hormones, fewer vascular protective factors and adapting differently to prenatal complications. Thus, the placenta could act as a mediator of various autism likelihood factors.  

To investigate how placental biology contributes to autism in a sexually-dimorphic manner, the Autism Research Centre is in the process of creating the first Autism Placenta Biobank, in collaboration with two specialist institutions: the Centre for Trophoblast Research in Cambridge (CTR), and the Tommy's Maternal Health network of the University of Manchester. This entails actively recruiting pregnant women with a first degree relative or child with autism, assessed through a screening questionnaire during pregnancy and asking them to donate their placentas to research. These are then compared to placentas from typical male and female pregnancies, where the pregnant woman has no first degree relative with an autism diagnosis.  

A successful PhD candidate will be included in this team of researchers and assist with:
1.    Recruiting participating women in Manchester and arranging for tissue transfer in Cambridge and the affiliated laboratories for testing and analysis.
2.    Helping analyse tissue morphology and protein distribution differences in the placentas.
3.    Helping analyse genomic data from the placentas (both methylome and transcriptome) and integrating findings with existing resources regarding brain development (e.g. post-mortem brain transcriptome) and autism (e.g. lists of autism candidate genes, derived from sequencing or genotyping studies).
4.    Locating additional sources for placental tissue and establish research collaborations, in order to add to the Biobank and replicate findings.  

This PhD will be part of a wider, multi-disciplinary research initiative that aims to understand the role of sex differences in neurodevelopment and autism likelihood.