Gene mutation behind female infertility identified

Scientists, including one of Indian origin, have uncovered a gene mutation that may provide answers to unexplained female infertility.
Researchers from Baylor College of Medicine in the US found that women with mutations that lead to loss-of-function of some of the genes of the NLRP family can fail to reproduce for reasons that may include recurrent loss of pregnancies with abnormally developing placentas, loss of the embryo before implantation, or, more rarely, having a baby with developmental disabilities.
"Experts cannot identify the cause of the problem in an estimated 10 to 15 per cent of couples with infertility and 50 per cent of women with recurrent pregnancy loss," said Ignatia B Van den Veyver of Baylor College of Medicine.

"Women carrying these mutations are healthy in all other physical aspects, so they are unaware that they have these mutations that do not allow them to carry a pregnancy," said Sangeetha Mahadevan of Baylor College of Medicine.
Researchers developed a mouse model to investigate the mechanisms by which the inactivation of the human NLRP2 and NLRP7 genes might affect reproductive success and fertility.
They genetically engineered mice to lack the Nlrp2 gene, the animals looked completely normal.

When the females mated, researchers observed three different types of outcomes: some did not get pregnant, others had stillborn pups with abnormalities and a third group of females gave birth to live pups of normal appearance, but fewer per litter.

In the mouse model lacking the Nlrp2 gene, the scientists also observed abnormal DNA methylation in the offspring, which allowed them to draw stronger parallels between the human and the mouse systems.
"We found that when the Nlrp2 gene is absent or inactive in the mother, the subcortical maternal complex does not form properly anymore in the egg and that, in addition, one of the proteins that plays a role in DNA methylation seems not to be in the right place in early embryos," said Mahadevan.
Researchers also attempted to grow the eggs of a female mouse carrying the mutation in the Nlrp2 gene in an artificial environment in the lab, however they did not develop.

The study was published in the journal Scientific Reports.