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The role of docosahexaenoic acid (DHA) in sperm morphogenesis and male fertility

Award Number: F32HD103333
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 08/16/2020
PERIOD OF PERFORMANCE END DATE: 01/07/2022

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The role of docosahexaenoic acid (DHA) in sperm morphogenesis and male fertility - PROJECT SUMMARY/ABSTRACT Docosahexaenoic acid (DHA) is an omega-3 (ω-3) dietary-derived essential polyunsaturated fatty acid (PUFA) present in particularly high levels in testes. DHA is a critical component of mitochondrial and cellular membranes that regulates membrane fluidity, susceptibility to oxidative stress, and membrane-protein interactions. Multiple studies using mouse models or analyzing human populations have clearly shown that DHA deficiency negatively impacts spermatogenesis to cause male infertility, and that supplementation with DHA improves semen quality and fertility. Unfortunately, Western diets are remarkably deficient in w-3 fatty acids, and therefore a majority of the world’s population is at risk for DHA-deficiency. Despite these clearly established links between DHA and male fertility, DHA’s role and mechanism of action in spermatogenic cells remain unknown. To address this, the Geyer lab (experts in spermatogenesis) has partnered with the Ellis lab (experts in lipid metabolism), and this unique partnership has provided the applicant (Dr. Ben Hale) with formal training in both disciplines. This training will enable Dr. Hale to pursue the long-term goals to define the roles of PUFAs in germ cell metabolism and sperm formation and function. The proposed project herein is an outgrowth of work from our group characterizing a new diet-independent genetic mouse model of DHA deficiency by whole-body deletion of ‘acyl-CoA synthetase 6’ (Acsl6), which encodes an enzyme essential for cellular DHA metabolism. We recently reported whole-body Acsl6 knockout (KO) mice have significantly reduced testicular DHA levels, multiple defects in spermatogenesis, and are severely subfertile. These Acsl6 KO mice are the ideal tool to define the specific mechanisms underlying DHA function in spermatogenesis. We will directly correlate defects in sperm function and morphogenesis to changes in germ cell lipid distribution. We will test the central hypothesis that ACSL6 is required to incorporate DHA into germ cell lipid membranes to facilitate sperm morphogenesis. This hypothesis will be tested in the following Aims: 1) Determine how Acsl6 KO sperm are defective, and 2) determine the roles of DHA during spermatogenesis. The completion of these Aims will provide an unprecedented understanding of how incorporation of DHA into the germ cell facilitates sperm morphogenesis and function.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2023 ( Subtotal = -$5,252 )
2023	2021	EAST CAROLINA UNIVERSITY	1000 E 5TH ST	GREENVILLE	NC	27858	PITT	USA	Child Health and Human Development Extramural Research	000	2	5/15/2023	NON-COMPETING CONTINUATION	-$5,252
														Subtotal = -$5,252

Issue Date FY: 2022 ( Subtotal = -$41,286 )
2022	2021	EAST CAROLINA UNIVERSITY	1000 E 5TH ST	GREENVILLE	NC	27858	PITT	USA	Child Health and Human Development Extramural Research	000	2	1/5/2022	NON-COMPETING CONTINUATION	-$41,286
														Subtotal = -$41,286

Issue Date FY: 2021 ( Subtotal = $70,458 )
2021	2021	EAST CAROLINA UNIVERSITY	1000 E 5TH ST	GREENVILLE	NC	27858	PITT	USA	Child Health and Human Development Extramural Research	000	2	7/2/2021	NON-COMPETING CONTINUATION	$70,458
														Subtotal = $70,458

Issue Date FY: 2020 ( Subtotal = $67,446 )
2020	2020	EAST CAROLINA UNIVERSITY	1000 E 5TH ST	GREENVILLE	NC	27858	PITT	USA	Child Health and Human Development Extramural Research	001	1	7/17/2020	NEW	$0
2020	2020	EAST CAROLINA UNIVERSITY	1000 E 5TH ST	GREENVILLE	NC	27858	PITT	USA	Child Health and Human Development Extramural Research	000	1	7/17/2020	NEW	$67,446
														Subtotal = $67,446

Grand Total All Awards = $91,366

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The role of docosahexaenoic acid (DHA) in sperm morphogenesis and male fertility

Award Number: F32HD103333

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 08/16/2020

PERIOD OF PERFORMANCE END DATE: 01/07/2022

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