Lack of placental neurosteroid alters cortical development and female somatosensory function
Placental endocrine function is essential to fetal brain development. Placental hormones include neurosteroids such as allopregnanolone (ALLO), a regulator of neurodevelopmental processes via positive allosteric modulation of the GABAA receptor (GABAA-R). Using a mouse model (plKO) in which the gene...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2022.972033/full |
| _version_ | 1811240986158825472 |
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| author | Dana Bakalar Jiaqi J. O’Reilly Helene Lacaille Jacquelyn Salzbank Jacob Ellegood Jason P. Lerch Toru Sasaki Yuka Imamura Kazue Hashimoto-Torii Claire-Marie Vacher Anna A. Penn |
| author_facet | Dana Bakalar Jiaqi J. O’Reilly Helene Lacaille Jacquelyn Salzbank Jacob Ellegood Jason P. Lerch Toru Sasaki Yuka Imamura Kazue Hashimoto-Torii Claire-Marie Vacher Anna A. Penn |
| author_sort | Dana Bakalar |
| collection | DOAJ |
| description | Placental endocrine function is essential to fetal brain development. Placental hormones include neurosteroids such as allopregnanolone (ALLO), a regulator of neurodevelopmental processes via positive allosteric modulation of the GABAA receptor (GABAA-R). Using a mouse model (plKO) in which the gene encoding the ALLO synthesis enzyme is specifically deleted in trophoblasts, we previously showed that placental ALLO insufficiency alters cerebellar white matter development and leads to male-specific autistic-like behavior. We now demonstrate that the lack of placental ALLO causes female-predominant alterations of cortical development and function. Placental ALLO insufficiency disrupts cell proliferation in the primary somatosensory cortex (S1) in a sex-linked manner. Early changes are seen in plKO embryos of both sexes, but persist primarily in female offspring after birth. Adolescent plKO females show significant reduction in pyramidal neuron density, as well as somatosensory behavioral deficits as compared with plKO males and control littermates. Assessment of layer-specific markers in human postmortem cortices suggests that preterm infants may also have female-biased abnormalities in cortical layer specification as compared with term infants. This study establishes a novel and fundamental link between placental function and sex-linked long-term neurological outcomes, emphasizing the importance of the growing field of neuroplacentology. |
| first_indexed | 2024-04-12T13:28:59Z |
| format | Article |
| id | doaj.art-1ea46f0c9d3a4f6d94de68feedfda90c |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-12T13:28:59Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-1ea46f0c9d3a4f6d94de68feedfda90c2022-12-22T03:31:14ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-10-011310.3389/fendo.2022.972033972033Lack of placental neurosteroid alters cortical development and female somatosensory functionDana Bakalar0Jiaqi J. O’Reilly1Helene Lacaille2Jacquelyn Salzbank3Jacob Ellegood4Jason P. Lerch5Toru Sasaki6Yuka Imamura7Kazue Hashimoto-Torii8Claire-Marie Vacher9Anna A. Penn10Center for Neuroscience Research, Children’s Research Institute, Children’s National Health System, Washington, DC, United StatesDivision of Neonatology, Department of Pediatrics, NewYork-Presbyterian Morgan Stanley Children’s Hospital, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, United StatesDivision of Neonatology, Department of Pediatrics, NewYork-Presbyterian Morgan Stanley Children’s Hospital, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, United StatesDivision of Neonatology, Department of Pediatrics, NewYork-Presbyterian Morgan Stanley Children’s Hospital, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, United StatesMouse Imaging Centre (MICe), Hospital for Sick Children, Toronto, ON, CanadaWellcome Centre for Integrative Neuroimaging (WIN), Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, United KingdomCenter for Neuroscience Research, Children’s Research Institute, Children’s National Health System, Washington, DC, United StatesDepartment of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, PA, United StatesCenter for Neuroscience Research, Children’s Research Institute, Children’s National Health System, Washington, DC, United StatesDivision of Neonatology, Department of Pediatrics, NewYork-Presbyterian Morgan Stanley Children’s Hospital, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, United StatesDivision of Neonatology, Department of Pediatrics, NewYork-Presbyterian Morgan Stanley Children’s Hospital, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, United StatesPlacental endocrine function is essential to fetal brain development. Placental hormones include neurosteroids such as allopregnanolone (ALLO), a regulator of neurodevelopmental processes via positive allosteric modulation of the GABAA receptor (GABAA-R). Using a mouse model (plKO) in which the gene encoding the ALLO synthesis enzyme is specifically deleted in trophoblasts, we previously showed that placental ALLO insufficiency alters cerebellar white matter development and leads to male-specific autistic-like behavior. We now demonstrate that the lack of placental ALLO causes female-predominant alterations of cortical development and function. Placental ALLO insufficiency disrupts cell proliferation in the primary somatosensory cortex (S1) in a sex-linked manner. Early changes are seen in plKO embryos of both sexes, but persist primarily in female offspring after birth. Adolescent plKO females show significant reduction in pyramidal neuron density, as well as somatosensory behavioral deficits as compared with plKO males and control littermates. Assessment of layer-specific markers in human postmortem cortices suggests that preterm infants may also have female-biased abnormalities in cortical layer specification as compared with term infants. This study establishes a novel and fundamental link between placental function and sex-linked long-term neurological outcomes, emphasizing the importance of the growing field of neuroplacentology.https://www.frontiersin.org/articles/10.3389/fendo.2022.972033/fullneuroplacentologyallopregnanolone (3α,5α-THP)somatosensory cortex (S1)placentapostmortem human brainpreterm birth |
| spellingShingle | Dana Bakalar Jiaqi J. O’Reilly Helene Lacaille Jacquelyn Salzbank Jacob Ellegood Jason P. Lerch Toru Sasaki Yuka Imamura Kazue Hashimoto-Torii Claire-Marie Vacher Anna A. Penn Lack of placental neurosteroid alters cortical development and female somatosensory function Frontiers in Endocrinology neuroplacentology allopregnanolone (3α,5α-THP) somatosensory cortex (S1) placenta postmortem human brain preterm birth |
| title | Lack of placental neurosteroid alters cortical development and female somatosensory function |
| title_full | Lack of placental neurosteroid alters cortical development and female somatosensory function |
| title_fullStr | Lack of placental neurosteroid alters cortical development and female somatosensory function |
| title_full_unstemmed | Lack of placental neurosteroid alters cortical development and female somatosensory function |
| title_short | Lack of placental neurosteroid alters cortical development and female somatosensory function |
| title_sort | lack of placental neurosteroid alters cortical development and female somatosensory function |
| topic | neuroplacentology allopregnanolone (3α,5α-THP) somatosensory cortex (S1) placenta postmortem human brain preterm birth |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2022.972033/full |
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